SNPMiner Trials by Shray Alag


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Report for Mutation C282Y

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 50 clinical trials

Clinical Trials


1 Hemochromatosis and Iron Overload Screening Study (HEIRS)

To determine the prevalence, genetic and environmental determinants, and potential clinical, personal, and societal impact of iron overload and hereditary hemochromatosis, in a multi-center, multiethnic, primary care-based sample of 100,000 adults. The study is conducted by the Division of Epidemiology and Clinical Applications of the NHLBI, the Division of Blood Diseases and Resources of the NHLBI, and the Ethical, Legal, and Social Implications (ELSI) Research Program of the NHGRI.

NCT00005541 Blood Disease Hemochromatosis Iron Overload
MeSH:Hematologic Diseases Hemochromatosis Iron Overload
HPO:Abnormality of blood and blood-forming tissues

Evidence suggests that early diagnosis and treatment can prevent disease manifestations and enable normal life expectancy The discovery of the HFE C282Y and H63D variants in the HLA gene region on chromosome 6 provides an opportunity for early and rapid genetic identification of individuals at risk for development of hereditary hemochromatosis. --- C282Y ---

In order to obtain data on the prevalence of genetic factors in a routine care population, a random subgroup of approximately 20-40 percent of the 101,000 screenees will be genotyped for known variants, such as HFE C282Y and H63D, related to iron metabolism and overload. --- C282Y ---


2 Studies of Phlebotomy Therapy in Hereditary Hemochromatosis

This study will evaluate the effectiveness of a test called MCV in guiding phlebotomy (blood drawing) therapy in patients with hemochromatosis an inherited disorder that causes too much iron to be absorbed by the intestine. The excess damages body tissues, most severely in the liver, heart, pancreas and joints. Because iron is carried in the hemoglobin of red blood cells, removing blood can effectively lower the body s iron stores. Patients with hemochromatosis undergo weekly phlebotomy treatments (1 pint per session) to deplete iron stores. This usually requires 10 to 50 treatments, after which blood is drawn every 8 to 12 weeks to prevent a re-build up of iron. A test that measures ferritin a protein involved in storing iron is commonly used to guide phlebotomy therapy in hemochromatosis patients. This study will compare the usefulness of the ferritin test with that of MCV, which measures red blood cell size, in guiding phlebotomy therapy. In addition, the study will 1) examine whether keeping iron levels low during maintenance therapy can help heal severe liver disease and improve arthritis in affected patients, and 2) design a system for making blood collected from hemochromatosis donors available for transfusion into other patients. Patients 15 years and older with diagnosed hemochromatosis or very high iron levels suggesting possible hemochromatosis may be eligible for this study. Candidates will have a history, physical evaluation, review of medical records and blood tests, and complete a symptoms questionnaire. Participants will have the following procedures: - Phlebotomy therapy every 1 to 2 weeks, depending on iron levels - Blood sample collection for blood cell counts and iron studies at every phlebotomy session - Blood sample collection (about 2 tablespoons) every 1 to 2 weeks after iron stores have been depleted - Phlebotomy every 8 to 12 weeks after iron stores are used up to prevent re-build up of excess iron With each blood donation that will be made available for transfusion to other patients, participants will answer the same health history screening questions and undergo the same blood tests given to all regular volunteer blood donors. These include screening for the HIV and hepatitis viruses and for syphilis. Patients who meet height and weight requirements may be asked to consider "double red cell" donations using apheresis. In this procedure, whole blood is collected through a needle placed in an arm vein, similar to routine phlebotomy. The blood then circulates through a machine that separates it into its components. The red cells are removed and the rest of the blood is returned to the body, either through the same needle or through a second needle in the other arm. Patients who have very high iron levels or an enlarged liver will be offered evaluation by the NIH Liver Service. Those judged to be at increased risk for cirrhosis may be advised to undergo a liver biopsy. If cirrhosis is found, the patient will be asked to consider a repeat biopsy after 3 to 5 years of continuous iron depletion to see if scarring has improved. Patients with arthritis will be offered evaluation by the NIH Arthritis Service and, depending on symptoms, may be advised to have X-ray studies or a joint biopsy.

NCT00007150 Hemochromatosis Procedure: Phlebotomy
MeSH:Hemochromatosis

- INCLUSION CRITERIA: Confirmed diagnosis of HH, defined by the following HFE genotypes: C282Y/C282 or C282Y/H63D. --- C282Y ---

Although the molecular pathophysiology remains incompletely understood, a homozygous mutation in the HFE gene (Cys282Tyr) is observed in nearly 100% of clinically confirmed cases. --- Cys282Tyr ---

Primary Outcomes

Description: Response to phlebotomy therapy in HH patients, as evidenced by iron-depletion

Measure: MCV drops 1-3% below baseline

Time: 4 to 12 months after starting phlebotomy therapy

3 Treatment of Nonalcoholic Steatohepatitis With Pioglitazone

This study will evaluate the effectiveness of pioglitazone, a new diabetes medicine, on decreasing insulin resistance and improving liver disease in patients with nonalcoholic steatohepatitis (NASH). NASH is a chronic liver disease with unknown cause that involves fat accumulation and inflammation in the liver, leading to liver cirrhosis in 10 to 15 percent of patients and significant liver scarring in another 30 percent. Although similar to a condition that affects people who drink excessive amounts of alcohol, NASH occurs in people who drink only minimal or no alcohol. It is most often seen in patients with insulin resistance. Pioglitazone decreases insulin resistance and improves blood lipid (fat) levels, so that it may improve liver disease in NASH. Patients with NASH 18 years of age or older may be eligible for this study. Candidates will be screened with a medical history and physical examination and routine blood tests. They will see a dietitian for counseling on diet and weight reduction, if needed. They will stop taking any medications for liver disease and take a daily multivitamin pill. After 2 months, those eligible for participation will be enrolled in the study. Participants will be admitted to the Clinical Center for 2 to 3 days for a complete medical history, physical examination, blood tests, urinalysis, chest X-ray, electrocardiogram, abdominal ultrasound and a liver biopsy. After the diagnosis of NASH is confirmed, the following procedures will be performed: - Echocardiography - imaging test using sound waves shows the heart structure and function - Resting metabolic rate - measures amount of oxygen (and calories) used to maintain body functions at rest. While lying down, the patient wears a clear plastic hood over the head for 20 minutes while the amount of oxygen used is measured. - Magnetic resonance imaging (MRI) scans - shows the size of the liver and other organs. The patient lies on a table in a metal cylinder that contains a magnetic field (the scanner) for no more than 30 minutes while the organs are imaged. - Dual energy X-ray absorptiometry (DEXA) scan measures whole body composition, including amount of fat. The patient lies under an X-ray scanning machine for about 2 minutes. - Oral glucose tolerance test (OGTT) - measures blood sugar and insulin levels. The patient drinks a very sweet drink containing glucose (sugar), after which blood samples are collected at various intervals during the 3-hour test. The blood is drawn through a catheter (thin plastic tube) placed in the arm before the test begins. - Intravenous glucose tolerance test (IVGTT) - determines how the tissues respond to insulin and glucose. Glucose is injected into a vein, followed by a short infusion of insulin. Blood samples are collected through a catheter at various intervals during the 3-hour test. When the above procedures are completed, patients start taking pioglitazone by mouth once a day for 48 weeks, keeping track of the medication and any side effects. They will be seen at the clinic every 2 weeks for the first month and then every 4 weeks for the rest of the treatment period. The visits will include an interview and examination by a physician and blood draw for laboratory tests. Female patients will have a pregnancy test at each clinic visit. At the end of the treatment period patients will be admitted to the Clinical Center for a repeat medical evaluation that will include the procedures described above.

NCT00013598 Fatty Liver Nonalcoholic Steatohepatitis Drug: Pioglitazone
MeSH:Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Hepatic steatosis

Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---


4 Long-Term Treatment of Nonalcoholic Steatohepatitis With Pioglitazone

Nonalcoholic steatohepatitis (NASH) is a common liver disease that resembles alcoholic hepatitis but occurs in persons who drink little or no alcohol. The etiology of NASH is unclear, but it is commonly associated with diabetes, obesity, and insulin resistance. Several pilot studies, including a study of pioglitazone at the NIH Clinical Center (01-DK-0130), have shown that the insulin-sensitizing thiazolidinediones lead to decreases in serum alanine aminotransferase (ALT) levels and improved liver histology. Once therapy is stopped, however, ALT levels rapidly return to pre-treatment values. Inaddition we are currently enrolling patients with NASH in a pilot study of metformin therapy for 48-weeks, however our results in 3 patients thus far have not been very encouraging. In the current study, patients who have completed the pilot study of pioglitazone and have been off therapy for 48 weeks will be offered re-treatment for 3 years. We also propose to treat patients who have not had a satisfactory response to metformin with pioglitazone for the same duration. After a repeat medical and metabolic evaluation and liver biopsy, patients with moderate-to-severe NASH (activity score greater than or equal to 4) will restart pioglitazone at a dose of 15 mg daily. If after 48 weeks, ALT levels are not normal or improved to the degree identified during the pilot study, the dose will be increased to 30 mg daily at the end of 3 years, all patients will undergo repeat medical and metabolic evaluation and liver biopsy. The primary end point will be improvement in liver histology. Secondary end points will be improvements in insulin sensitivity, reduction in visceral fat, liver volume, and liver biochemistry. The aim of this study is to evaluate whether long-term pioglitazone therapy can safely achieve and maintain biochemical and histological improvements in NASH. ...

NCT00062764 Hepatitis Drug: Actos (Pioglitazone)
MeSH:Hepatitis Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Hepatic steatosis Hepatitis

Hemochromatosis as defined by presence of 3+ or 4 iron on liver biopsy stain and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Primary Outcomes

Description: A histological response was defined as a reduction in the NASH activity index by 3 points or more with improvements of at least 1 point each in steatosis, parenchymal inflammation, and hepatocellular injury.

Measure: Number of Patients With Improvement in Liver Histology

Time: 48 weeks

Secondary Outcomes

Measure: Number of Patients With Impaired Glucose Tolerance After Treatment

Time: 48 weeks

Measure: Mean Increase of Insulin Sensitivity Index

Time: 48 weeks

Measure: Average Increase in Weight After Treatment

Time: 48 weeks

Measure: Mean BMI Change

Time: 48 weeks

5 Treatment of Nonalcoholic Steatohepatitis With Metformin

Nonalcoholic Steatohepatitis (NASH) is associated with progressive liver disease, fibrosis, and cirrhosis. Although the cause of NASH is unknown, it is often associated with obesity, type 2 diabetes, and insulin resistance. At present, there are no approved treatments for NASH patients, but an experimental approach has focused on improving their insulin sensitivity. Metformin is one of the most commonly used medications for the treatment of diabetes. The purpose of this study is to determine whether the medical problems of NASH patients, specifically liver damage, improves when their insulin sensitivity is enhanced with metformin. The study will last 3 to 5 years and will enroll up to 30 patients. Participants will undergo a complete medical examination, a series of lab tests, and a liver biopsy. They will then start taking a single 500-mg tablet of metformin once a day for 2 weeks, then the same dosage twice a day for 2 more weeks, if they tolerate the first dosage. The dosage will increase to 1,000 mg twice a day for the remaining 44 weeks of the study. After 1 year, participants will undergo a repeat medical examination and liver biopsy.

NCT00063232 Hepatitis Drug: Metformin
MeSH:Hepatitis Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Hepatic steatosis Hepatitis

7. Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Primary Outcomes

Description: Patients under went liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint is a three point improvement in the histological NASH activity index with a decrease in at least two of the component scores and no worsening of fibrosis or increase in Mallory bodies.

Measure: Change in the Histological NASH Activity Index at 48 Weeks Compared With Baseline (Number of Participants in Each Change Category)

Time: from baseline to 48 Weeks

Secondary Outcomes

Description: Alanine transaminase <42 U/L is considered normal

Measure: Change in Serum Alanine Aminotransferase (ALT) Levels From Baseline (Number of Participants in Each Change Category)

Time: from baseline to 48 weeks

Description: HOMA-IR is calculated from Fasting Glucose and Fasting Insulin

Measure: Change in Insulin Sensitivity (Glucose Tolerance, Homeostatic Model Assessment of Insulin Resistence (HOMA-IR)) From Baseline

Time: from baseline to 48 weeks

6 Characterization of Cardiac Function in Subjects With Hereditary Hemochromatosis Who Are New York Heart Association Functional Class I

This study will examine the effect of iron buildup in the hearts of patients with hereditary hemochromatosis (HH), a genetic disease that causes the body to accumulate excess amounts of iron. The excess iron can damage the heart, liver, pancreas, skin, and joints. Generally, early treatment with phlebotomy (periodic removal of a unit of blood), and in some cases chelation (using a drug to remove iron from the body) slows down organ damage in HH patients. This study will try to elucidate the effect of iron buildup in the heart and determine if phlebotomy and chelation help keep the heart healthy. Patients with HH and healthy volunteers 21 years of age and older may be eligible for this study. (Normal volunteers will provide normal values of heart function that will be used to verify abnormalities detected in HH patients.) Patients must have a gene abnormality of Hfe gene Cys282Try homozygote. They may or may not be receiving treatment for HH and they must have no heart symptoms or serious organ damage due to HH. Candidates will be screened with a medical history and physical examination, blood tests, electrocardiogram (EKG), Holter EKG (24-hour EKG monitoring, see description below), and chest x-ray. Participants will undergo the following tests and procedures over 2 to 5 days: - Exercise test: The participant exercises on a treadmill while wearing a mouthpiece, which is used to measure how much oxygen is used. Electrodes placed on the chest and arms monitor the heartbeat during the test. - Echocardiography: This ultrasound test uses sound waves to take pictures. A small probe is held against the chest to allow a technician to take pictures of the heart and assess its function. A drug called Optison may be injected in an arm vein if needed to enhance the ultrasound images. - Exercise stress echocardiography: The participant exercises on a stationary bike while heart function is measured with an echocardiogram, EKG, and blood pressure cuff. - 24-hour Holter EKG: The participant wears a small machine that records heart rhythm continuously for 24 hours. The recorder is connected by cables to electrodes placed on the chest. - Magnetic resonance imaging: This test uses a magnetic field and radio waves to obtain detailed images of the heart and blood vessels. The participant lies flat on a table that slides inside the scanner, which is a large hollow tube. All tests are performed once in normal volunteers and in patients who have received standard treatment for HH. Untreated patients repeat the tests 6 months after beginning phlebotomy or chelation. Additional time points for these tests might be added if further evaluation is needed.

NCT00068159 Hereditary Hemochromatosis
MeSH:Hemochromatosis

- INCLUSION CRITERIA: HH Patients Group A patients (untreated HH patients) Adults 21 years or older New York Heart Association Functional Classification Class I Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum ferritin level above 400 ng/ml or documented % iron saturation more than 60%. --- Cys282Tyr ---

Group B patients (treated HH patients) Adults 21 years or older New York Heart Association Functional Classification Class I Documented positive phenotyping for homozygote Cys282Tyr of Hfe gene with documented serum ferritin level above 400 ng/ml or documented % iron saturation more than 60%. --- Cys282Tyr ---

No symptoms suggestive of heart disease or any other medical conditions, negative Hfe genotyping for Cys282Tyr or His63Asp with normal ferritin and iron saturation. --- Cys282Tyr ---

Homozygosity for the Cys282Tyr mutation, which is the most common known mutation with a predisposition to iron overload, occurs with an estimated frequency of 8 per 1000 in the Caucasians. --- Cys282Tyr ---

Although the pathophysiology remains incompletely understood, a homozygote mutation in Cys282Tyr is present in 84 to 100% of clinically confirmed HH cases. --- Cys282Tyr ---

Primary Outcomes

Description: To assess detailed cardiac function using non-invasive cardiac imaging in Group A; untreated-NYHA Class I HH subjects without conventional therapy for HH, Group B; treated- NYHA Class I HH subjects with conventional phlebotomy and/or iron chelation therapy and compare these results to those from Group C; age-gender matched healthy control volunteers.

Measure: Echocardographic variable early diastolic peak tissue Doppler velocity of septal mitral annulus (Em).

Time: Baseline, 1, 2, and 5 years

Secondary Outcomes

Description: To compare the results of the cardiac functional abnormalities in HH to those from healthy control volunteers

Measure: Exercise testing variable change in ejection fraction in response to exercise

Time: Baseline only

7 A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Twice-Weekly Peginterferon Alpha 2a and Ribavirin Induction Therapy for Chronic Hepatitis C in Patients Who Are Coinfected With HIV-1

This study will evaluate the safety and effectiveness of combination therapy with peginterferon alpha-2a and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. Peginterferon alpha with ribavirin is the therapy of choice for people with HCV alone. Peginterferon alpha-2a is a compound that results from attaching a polyethylene glycol molecule to interferon alpha-2a. This compound stays in the blood longer than unmodified interferon alpha-2a, causing a higher blood concentration and thus maintaining greater activity against the hepatitis C virus. HIV-infected patients 18 years of age and older with chronic hepatitis C infection and a viral load greater than 2000 copies/mL may be eligible for this 2-1/2 year study. Candidates are screened with a medical history and physical examination, blood and urine tests, eye examination, chest x-ray, electrocardiogram (EKG), liver ultrasound, and pregnancy test in women who are able to become pregnant. If a recent liver biopsy is not available, this test is done to determine the type and severity of liver disease. The patient is given a sedative before the procedure. Then, the skin in the area over the biopsy site is numbed with a local anesthetic and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. The patient remains in the hospital overnight for monitoring. Participants begin treatment with injections under the skin of peginterferon alpha-2a and ribavirin pills by mouth on study day 0. Peginterferon is given either once or twice a week for 4 weeks and then once a week for 44 weeks. Ribavirin is given daily. In addition, patients continue to take all other medications prescribed by their doctor. Clinic visits are scheduled for the following procedures: - Days 1, 3, 4, 7, 10 and weeks 2, 3, and 4 - Blood tests for safety measures and to measure blood levels of HIV and HCV. - Weeks 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection. In addition, eye examinations are done every 3 months, and pregnancy and thyroid function tests are done several times during the treatment period. - Week 48 or end of treatment - Treatment stops after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients return to the clinic for a chest x-ray, EKG, blood tests, and abdominal ultrasound. Patients are hospitalized for a repeat liver biopsy. - Weeks 52, 56, 64 and 72 - Blood and urine tests to determine the side effects of treatment and its effect on the HCV infection, and a urine pregnancy test in women.

NCT00085917 Hepatitis C HIV Infections Drug: Double dose pegylated interferon with weight based Ribavirin Drug: standard dose pegylated interferon alfa -2a and ribavirin
MeSH:Hepatitis A Hepatitis C Hepatitis
HPO:Hepatitis

- Hemochromatosis or secondary iron overload as defined by (1) an elevated serum ferritin or an iron saturation (serum iron/IBC X 100%) of greater than 50% and (2) presence of 3+ or more stainable Iron on liver biopsy according to the study pathologist or a history of previous phlebotomy for Iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. --- C282Y ---

Those who have compound heterozygosity to C282Y and H63D are also not eligible. --- C282Y ---

Primary Outcomes

Description: SVR [ Sustained virological response] SVR was defined as HCV RNA levels below the limit of detection 24 weeks after the end of treatment.

Measure: Number of Participants With Sustained Virologic Response (SVR)

Time: 72 weeks

Secondary Outcomes

Description: normalization of liver enzymes :Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) Alanine aminotransferase (ALT): Normal 6 - 41 U/L Aspartate aminotransferase (AST) : Normal 9 - 34 U/L

Measure: Number of Participants With Normalization of Liver Enzymes

Time: week 24, week 48, week 72

Description: Adverse Events - Anemia, Neutropenia and Psychiatric adverse events

Measure: Number of Participants With Adverse Events

Time: 48 weeks

8 S-Adenosyl Methionine for Symptomatic Treatment of Primary Biliary Cirrhosis

This study will examine the effect of S-adenosyl methionine (SAMe) on itching and fatigue in patients with primary biliary cirrhosis, a disease of the small bile ducts in the liver. Ursodiol, the only currently available treatment for biliary cirrhosis, does not cure the disease, and many people continue to have symptoms or liver test abnormalities despite treatment. SAMe is a naturally occurring substance found in most cells of the body. The highest levels of the substance are produced by the liver, where it helps to rid the body of toxins and breakdown products of metabolism. Studies in Europe suggest that SAMe may help to: 1) decrease the fatigue and itching that are common in persons with liver problems, and 2) decrease levels of liver enzymes in the blood, suggesting that it may decrease the amount of liver injury. Patients 21 years of age or older with primary biliary cirrhosis who are taking ursodiol and have symptoms of itching or fatigue may be eligible for this study. Candidates are screened with a medical history, physical examination, review of medical records, routine blood tests, and a symptoms rating scale. Participants stop all medications for itching 4 weeks before starting the study, but continue to take ursodiol during the 42-week trial. On entering the study, patients are assigned to take either SAMe or placebo tablets twice a day for 12 weeks. While taking the medications, they are followed in the clinic every 2 weeks for the first month and then every 4 weeks to fill out symptoms questionnaires and have a short medical evaluation and blood tests. At the end of 12 weeks, treatment is interrupted for a 2-week "wash-out" period, after which patients begin a 12-week crossover treatment; that is, patients who were taking SAMe are switched to placebo, and those who were taking placebo are switched to SAMe. After completing the second 12-week treatment course, patients come to the clinic at 4, 8, and 12 weeks to fill out symptoms questionnaires and have a medical evaluation and blood tests. At the last visit, patients are told which type of tablet they received during the two courses of treatment. SAMe is available without prescription in many forms as an over-the-counter medication.

NCT00125281 Liver Cirrhosis, Biliary Drug: S-adenosyl-methionine (SAMe) capsules
MeSH:Liver Cirrhosis Liver Cirrhosis, Biliary Fibrosis
HPO:Biliary cirrhosis Cirrhosis Hepatic fibrosis

Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Patients with iron saturation indices of greater than 45% and serum ferritin levels of greater than 300 ng/ml for men and greater than or equal to 250 ng/ml for women will undergo genetic testing for C282Y and H63D. --- C282Y ---

Primary Outcomes

Measure: Improvement in symptoms as assessed by validated questionnaires and visual analogue scales administered at 2 to 4 week intervals during therapy.

Time: 12 weeks of therapy

Secondary Outcomes

Measure: Improvement in serum alanine aminotransferase and alkaline phosphatase.

Time: 12 weeks

9 Cytochrome P450 2E1 and Iron Overload

The aim of the study is to determine, in patients presenting hepatic iron overload (genetic haemochtomatisis or dysmetabolic iron overload syndrome), the effects of venesection therapy on cytochrome P450 2E1 activity by comparing the rates of metabolization of chlorzoxazone before and after venesection.

NCT00138684 Insulin Resistance Iron Overload Procedure: venesection
MeSH:Insulin Resistance Iron Overload
HPO:Insulin resistance

Inclusion Criteria: - Male patients aged from 18 to 70 years - Hepatic iron overload measured by magnetic resonance imaging [MRI] (> 36 µmol/g and < 200 µmol/L) - Homozygosity for the C282Y mutation of the HFE or dysmetabolic iron overload syndrome (DIOS) based on the presence of at least one of these following metabolic abnormalities: - Overweight: BMI > 25 kg/m2 - Waist/hip circumference (cm) > 0.90 - Diabetes mellitus (fasting blood glucose level >1.25g/L or blood glucose level after 2 hours > 2g/L) or glucose intolerance (fasting blood glucose level between 1.10 and 1.25g/L) - Total cholesterolemia > 6.2 mmol/L or HDL-Cholesterol < 0.9 mmol/L - TG>= 1.7 mmol - Written informed consent Non-Inclusion Criteria: - Consumption of alcohol > 50 g/day and of any CYP2E1 inhibitor substances - Smoker > 5 cigarets/day - History of blood donation or venesection - Other causes of iron overload: aceruloplasminaemia, haematological disorder (abnormal blood counting), late cutaneous porphyria (cutaneous bullous disorders and photosensibilisation) , martial treatment, repeated transfusions. --- C282Y ---

- Inflammatory syndrome (CRP > 3ng/ml) Inclusion Criteria: - Male patients aged from 18 to 70 years - Hepatic iron overload measured by magnetic resonance imaging [MRI] (> 36 µmol/g and < 200 µmol/L) - Homozygosity for the C282Y mutation of the HFE or dysmetabolic iron overload syndrome (DIOS) based on the presence of at least one of these following metabolic abnormalities: - Overweight: BMI > 25 kg/m2 - Waist/hip circumference (cm) > 0.90 - Diabetes mellitus (fasting blood glucose level >1.25g/L or blood glucose level after 2 hours > 2g/L) or glucose intolerance (fasting blood glucose level between 1.10 and 1.25g/L) - Total cholesterolemia > 6.2 mmol/L or HDL-Cholesterol < 0.9 mmol/L - TG>= 1.7 mmol - Written informed consent Non-Inclusion Criteria: - Consumption of alcohol > 50 g/day and of any CYP2E1 inhibitor substances - Smoker > 5 cigarets/day - History of blood donation or venesection - Other causes of iron overload: aceruloplasminaemia, haematological disorder (abnormal blood counting), late cutaneous porphyria (cutaneous bullous disorders and photosensibilisation) , martial treatment, repeated transfusions. --- C282Y ---

Primary Outcomes

Measure: variation of chlorzoxazone metabolization rate measured before and after venesection

Time: Baseline and after iron desaturation completion

Secondary Outcomes

Measure: variation of blood Malonedialdehyde rate

Time: Baseline and after iron desaturation completion

Measure: variation of blood 4-hydroxynonenal rate

Time: Baseline and after iron desaturation completion

Measure: variation of blood Glutathion rate

Time: Baseline and after iron desaturation completion

Measure: variation of serum Vitamin E rate

Time: Baseline and after iron desaturation completion

Measure: Variation of serum Vitamin C rate

Time: Baseline and after iron desaturation completion

10 Iron Depletion Therapy for Patients With Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease

The purpose of this study is to find out whether lowering the amount of iron in the body will result in less resistance to insulin and improved liver function in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. This may result in better diabetes control and/or a decrease in the amount of liver fat.

NCT00230087 Non-Alcoholic Fatty Liver Disease Diabetes Mellitus Procedure: blood donation
MeSH:Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Diabetes Mellitus
HPO:Abnormality of the liver Decreased liver function Diabetes mellitus Elevated hepatic transaminase Hepatic steatosis

- Hemoglobin HbA1c level ≤ 8 % - Serum ALT levels ≥1.3 x ULN - Between 18-65 years of age Exclusion Criteria - Hereditary hemochromatosis or hepatic iron overload defined as any of the following: - 2+ iron on hepatic iron staining - Hepatic Iron Index ≥ 1.9 - C282Y homozygous or C282Y/H63D compound heterozygous HFE genotype - Use of insulin or thiazolidinediones for the treatment of diabetes - Use of anti-NASH drugs (thiazolidinediones, vitamin E, UDCA, SAM-e, betaine, milk thistle, gemfibrozil, anti-TNF therapies, probiotics) - Serum ferritin <50μg/L - Serum transferrin-iron saturation <10 % - Hemoglobin <10 mg/L - Hematocrit <38 % - Voluntary blood donation or therapeutic phlebotomy within the previous twelve months (except routine lab tests) - Pregnant or lactating women - Prior history of coronary artery disease, myocardial infarction, exertional dyspnea or chronic chest pain at rest. - Evidence of myocardial infarction as determined by an ECG Inclusion Criteria - Histological evidence of NAFLD and enrollment in NASH CRN Database Study - Type 2 DM treated with diet or a stable dose of non-insulin sensitizing oral hypoglycemic agents for > 3 mo. --- C282Y ---

- Hemoglobin HbA1c level ≤ 8 % - Serum ALT levels ≥1.3 x ULN - Between 18-65 years of age Exclusion Criteria - Hereditary hemochromatosis or hepatic iron overload defined as any of the following: - 2+ iron on hepatic iron staining - Hepatic Iron Index ≥ 1.9 - C282Y homozygous or C282Y/H63D compound heterozygous HFE genotype - Use of insulin or thiazolidinediones for the treatment of diabetes - Use of anti-NASH drugs (thiazolidinediones, vitamin E, UDCA, SAM-e, betaine, milk thistle, gemfibrozil, anti-TNF therapies, probiotics) - Serum ferritin <50μg/L - Serum transferrin-iron saturation <10 % - Hemoglobin <10 mg/L - Hematocrit <38 % - Voluntary blood donation or therapeutic phlebotomy within the previous twelve months (except routine lab tests) - Pregnant or lactating women - Prior history of coronary artery disease, myocardial infarction, exertional dyspnea or chronic chest pain at rest. - Evidence of myocardial infarction as determined by an ECG Non-Alcoholic Fatty Liver Disease Diabetes Mellitus Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Diabetes Mellitus Nonalcoholic fatty liver disease (NAFLD) is a common liver disease in the United States. --- C282Y ---

Primary Outcomes

Measure: Improved insulin sensitivity as determined by:(1) hyperinsulinemic euglycemic clamp method

Time: one year

Measure: (2) HOMA model- determined by the OGTT method

Time: one year

Secondary Outcomes

Measure: Change in serum aminotransferase levels Change in levels of serum, plasma and urinary markers of oxidative stress

Time: one year

Measure: Changes in intrahepatic and intraabdominal fat content as determined by CT scan

Time: one year

Measure: Change in serum levels of proinflammatory cytokines (ie IL-6, TnF-αR2)

Time: one year

11 Study of the Effects of Muscular Activity on Iron Metabolism: A Pilot Study on Healthy Volunteers

The aim of this study is to evaluate the effect of muscular exercise on iron metabolism in healthy volunteers. Fourteen healthy male subjects will have to pedal on an ergocycle for 45 minutes, and urine and blood samples will be collected regularly to measure hemojuvelin, hepcidin, iron and transferrin levels.

NCT00378469 Iron Overload Iron Deficiency Behavioral: 45 minute exercise on ergocycle
MeSH:Iron Overload

Inclusion Criteria: - Male individuals aged between 18 and 40 years old - Body mass index (BMI) between 18 and 25 - Normal at clinical examination - Normal biological variables - Written informed consent Exclusion Criteria: - Mutation C282Y of the HFE gene - Iron metabolism abnormality - Inflammatory syndrome - Chronic pathology or ongoing treatment - Tobacco smoking, alcohol consuming more than 30g/day - History of transfusion or blood-giving within 3 months - Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV. --- C282Y ---

Primary Outcomes

Measure: Pharmacokinetics of urinary hepcidin

Measure: Pharmacokinetics of blood hemojuvelin

Secondary Outcomes

Measure: Pharmacokinetics of urine and blood iron, transferrin, interleukin-6 (IL-6) and ferritin

12 A Phase I/II Open Label, Dose Escalation Trial and a Six Month Extension to Explore the Safety and Efficacy of ICL670 in Patients With Iron Overload Resulting From Hereditary Hemochromatosis.

Brief Summary: This study was designed to explore a safe dose and characterize the preliminary safety and efficacy of ICL670 in adult patients with previously documented history of homozygous C282Y.

NCT00395629 Iron Overload Hereditary Hemochromatosis Drug: Deferasirox (ICL670)
MeSH:Hemochromatosis Iron Overload

A Phase I/II Open Label, Dose Escalation Trial and a Six Month Extension to Explore the Safety and Efficacy of ICL670 in Patients With Iron Overload Resulting From Hereditary Hemochromatosis.. Safety and Efficacy of Deferasirox (ICL670) in Patients With Iron Overload Resulting From Hereditary Hemochromatosis Brief Summary: This study was designed to explore a safe dose and characterize the preliminary safety and efficacy of ICL670 in adult patients with previously documented history of homozygous C282Y. --- C282Y ---

The mean trough concentration at each time point was calculated.. Inclusion Criteria: - Age 18 years of age or older - Male or female patients homozygous for the C282Y mutation. --- C282Y ---

Inclusion Criteria: - Age 18 years of age or older - Male or female patients homozygous for the C282Y mutation. --- C282Y ---

Primary Outcomes

Description: Mean absolute change in serum ferritin from baseline to the end of the extension study.

Measure: Absolute Change of Serum Ferritin From Baseline to the End of Extension, by Dose Cohort (Extension Per-protocol Population)

Time: 0 to 48 weeks

Secondary Outcomes

Description: A blood sample was collected just prior to administration of the next dose of Deferasirox (pre-dose trough level) or approximately 24 hours after the previous dose at weeks 4, 8, 12, 16, 20 and 24. The mean trough concentration at each time point was calculated.

Measure: Trough Concentrations of Deferasirox (ICL670), by Dose Cohort (Per-protocol Population)

Time: 4, 8, 12, 16, 20, and 24 weeks

13 Efficacy and Safety of Ursodesoxycholic Acid in the Management of Non-Alcoholic Steatohepatitis

This is a phase II study with direct individual benefit. It is a randomized, double blind placebo controlled study whose aim is to evaluate the efficacy and tolerance of ursodesoxycholic acid in patients who have been diagnosed with non-alcoholic steatohepatitis. The hepatoprotective effects of ursodesoxycholic acid may ameliorate the hepatic impairment associated with non-alcoholic steatohepatitis leading to subsequent significant decreases in transaminase elevations and non-invasive markers for hepatic fibrosis A positive response is defined as a significantly larger decrease in average ALAT levels between the time of inclusion in the study and the end of the treatment for the ursodesoxycholic acid group as compared to the placebo group. The duration of the study will be 12 months. An end of treatment evaluation (EoT) will take place at the end of the 12th month of treatment.

NCT00470171 Serum Levels of ALAT Transaminases Serum Markers for Fibrosis and Hepatic Inflammation Drug: Ursodesoxycholic acid
MeSH:Fatty Liver Non-alcoholic Fatty Liver Disease Inflammation
HPO:Hepatic steatosis

- Alcohol consumption of >20 g/day for women and > 30 g/day for men - Hepatitis from other causes: chronic viral hepatitis B or C, elevated ferritin levels associated with C282Y homozygosity, primary biliary cirrhosis, primary sclerosing cholangitis, well documented auto-immune hepatitis (specific autoantibodies, hypergammaglobulinemia, consistent histologic changes), alpha1 antitrypsin deficiency, Wilson's disease, HIV infection. --- C282Y ---

Primary Outcomes

Measure: A positive response is defined as a significantly larger decrease in average ALAT levels between the time of inclusion in the study and the end of the treatment for the ursodesoxycholic acid group as compared to the placebo group.

14 Effects of S-Adenosyl Methionine (SAMe) on Viral and Cell Signaling Response to Combination Therapy for Chronic Hepatitis C

This study will examine the effectiveness of S-adenosyl methionine (SAMe) in combination with peginterferon and ribavirin for treating hepatitis C virus. One out of three patients with hepatitis C develops cirrhosis of the liver, which can lead to liver failure or liver cancer. SAMe is a nutritional supplement that is made naturally in all cells of the body and acts to improve how the body handles stress. In laboratory experiments with liver cells, SAMe decreases the injury caused by liver toxins and improves the ability of interferon to block hepatitis C virus. Patients 18 years of age and older with hepatitis C infection who did not respond successfully to prior treatment with interferon and ribavirin or peginterferon and ribavirin may be eligible for this study. Participants receive the following treatment: - Peginterferon (given by injection) and ribavirin (taken by mouth) for 2 weeks - Washout period (no medications) for 4 weeks - SAMe (taken by mouth) for 2 weeks - Peginterferon, ribavirin and SAMe for 12-48 weeks, depending on patient response to treatment. Participants have a thorough physical evaluation before beginning treatment and again at the study's end. After starting treatment, patients return for clinic visits and blood tests weekly for the first several weeks, then less frequently (at 2-week, then 4-week and 8-week intervals until up to 72 weeks) to monitor symptoms, drug side effects, hepatitis C virus levels, liver enzyme levels and immune responses to hepatitis C. ...

NCT00475176 Chronic Hepatitis C Drug: Peginterferon alfa-2a Drug: Ribavirin Drug: S-adenosyl methionine for Chronic Liver Disease
MeSH:Hepatitis A Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic
HPO:Chronic active hepatitis Chronic hepatitis Hepatitis

- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Patients with iron saturation indices of greater than 45% and serum ferritin levels of greater than 300 ng/ml for men and greater than 250 ng/ml for women will undergo genetic testing for C282Y and H63D. --- C282Y ---

Primary Outcomes

Description: Improvement of slopes of decline in hepatitis C virus Ribonucleic acid in second course compared with first course in days 7 to 14 of therapy

Measure: Improvement in Viral Kinetics During the First 2 Weeks of Therapy

Time: Days 7 to 14 of therapy

Secondary Outcomes

Description: 2-log decline in HCV RNA by week 12 (early virological response) and sustained eradication of HCV RNA (sustained virological response).

Measure: 2-log Decline in HCV RNA by Week 12 (Early Virological Response) and Sustained Eradication of HCV RNA (Sustained Virological Response).

Time: 12 weeks from start of therapy

15 An Open Label Non-Randomized Trial to Assess Safety and Tolerability of Alb-Interferon Alfa 2b Every Two Weeks With Ribavirin Among HIV/HCV Coinfected Individuals

This study will determine if Albumin-linked interferon (Albinterferon alfa-2b) every 2 weeks is safe and tolerated by patients infected by both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). This is a new medication developed for HCV. It may help the immune system fight infections, especially those caused by viruses. Albinterferon alfa-2b appears quite similar to other interferons, in side effects and action in controlling HCV. Patients ages 18 and older who are infected with HCV genotype 1, are HIV positive, are infected with HCV, and have evidence of HCV-induced liver disease; and who are not pregnant or breast feeding may be eligible for this study. Many visits to NIH over a 76-week period are required. There will be collection of blood and urine, pregnancy test, and tests of HCV in the blood. A liver biopsy is required before start of the study if patients have not had one within 1 year. Another is done at the end of 72 weeks. An eye exam is done before start of the study and repeated later. An optional procedure called automated pheresis is done at the study beginning. Researchers can study patients' immunity to control HCV. Blood is drawn through a needle in an arm vein and spun in a machine to separate the desired blood component. Remaining blood is returned to the patient. Patients will receive Albinterferon alfa-2b at a dose of 900 mcg every 2 weeks for 48 weeks, by injection under the skin. Ribavirin is given at 1,000 mg or 1,200 mg by mouth twice daily, depending on a patient's weight. Side effects of Albinterferon alfa-2b are fatigue, headache, joint and muscle pain, and sleeplessness. The major side effect of ribavirin is anemia. Visits ranging from week 3 to 44 will determine the safety of Albinterferon alfa-2b and ribavirin and to see effects on reducing the HCV viral load. For weeks 48, 52, 56, 64, 72, and 76, patients will return for a clinic visit and blood tests. At week 72, an abdominal ultrasound and liver biopsy are done. Week 76 includes discussion of biopsy results.

NCT00489385 HIV Infections HCV Drug: Albinterferon Drug: Ribavirin Drug: Albuferon
MeSH:HIV Infections

Those subjects with, or a history of previous phlebotomy for iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. --- C282Y ---

Those who have compound heterozygosity to C282Y and H63D are also not eligible. --- C282Y ---

Primary Outcomes

Measure: Safety and tolerability of two doses of Albinterferon alpha 2b with ribavirin.

Secondary Outcomes

Measure: Histologic, virologic responses to Albinterferon alpha 2b and ribavirin

16 Therapeutic Effect of Erythrocyte Apheresis as Compared to Full Blood Phlebotomy in Patients With Hereditary Hemochromatosis

Primary hemochromatosis is the most frequent hereditary condition in Scandinavia. The condition may result in serious organ damage which can be prevented by therapy, but only few patients develop such organ damage. The optimal treatment, therefore, is still a matter of discussion Prevention of organ damage has traditionally been accomplished by drawing of full blood (phlebotomy), which has to be frequently repeated during the initial phase and then continued indefinitely as a maintenance treatment. The removed amount of iron may be increased two- or threefold for each procedure by using modern equipment for selective removal of red blood cells (red cell apheresis). Possible drawbacks of this technique may be higher costs, prolonged time for each therapeutic procedure, and certain requirements to the patients. The possible advantages are the reduced number of therapeutic procedures and less strain for the patient. No larger, randomized study has been published in order to determine which method should be preferred. This study is a controlled trial in which participating patients are asked to be randomized to red cell apheresis or traditional phlebotomy. Each group will be followed by means of well-defined assessments in order to explore possible advantages and disadvantages of each method in order to establish what type of treatment should be recommended.

NCT00509652 Hemochromatosis Procedure: Arm 1: Erythrocyte apheresis Procedure: Arm 2: Whole blood phlebotomy
MeSH:Hemochromatosis

Inclusion Criteria: 1. Diagnosis - Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---

- Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---

Exclusion Criteria: 1. Contra-indications to either treatment modality 2. Patients who are not able to co-operate 3. Lack of informed consent Inclusion Criteria: 1. Diagnosis - Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---

However, the criteria for ferritin levels have been set at 300 micrograms/L for patients who are homozygous for the C282Y mutation, and also heterozygous individuals will be included if ferritin is higher than 500 micrograms/L. --- C282Y ---

Inclusion criteria 1. Diagnosis 1. Individuals who art homozygous for C282Y or H63D or "compound heterozygous" for these tow variants and have ferritin levels higher than 300 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---

2. Individuals heterozygous for C282Y or H63D if ferritin levels higher than 500 micrograms/L or transferrin saturation higher than 50%. --- C282Y ---

Primary Outcomes

Measure: Decline in ferritin levels and transferrin saturation

Secondary Outcomes

Measure: Decline in hemoglobin levels

Measure: Patient discomfort during therapeutic procedure

Measure: Time consumption

Measure: Costs

17 Effect of Iron Depletion by Phlebotomy Plus Lifestyle Changes vs. Lifestyle Changes Alone on Liver Damage in Patients With Nonalcoholic Fatty Liver Disease With Increased Iron Stores

Patients will be randomized to lifestyle changes alone or lifestyle changes associated with iron depletion. Iron depletion will be achieved by removing 350 cc of blood every 10-15 days according to baseline hemoglobin values and venesection tolerance, until ferritin < 30 ng/ml and transferrin saturation < 25%. Weekly phlebotomies will be allowed for carriers of the C282Y HFE mutation. Smaller phlebotomies (250 cc) will be allowed for carriers of beta-thalassaemia trait. Maintenance phlebotomies (as much as required) will then be instituted to keep iron stores depleted (ferritin < 50 ng/ml and transferrin saturation < 25%, MCV <85 fl). Before starting treatment, patients will undergo ECG, and in the presence of hyperglycemia or hypertension also echocardiography (see exclusion criteria). Change in diabetes medication dosage or start of new therapy will be allowed for HbA1C values <6% or ≥ 7%. According to accepted criteria, previously untreated patients should be treated with metformin. If possible, newly diagnosed hypertension should be treated with Ace-inhibitors.

NCT00658164 Nonalcoholic Fatty Liver Disease Other: Iron depletion treatment
MeSH:Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Abnormality of the liver Decreased liver function Elevated hepatic transaminase Hepatic steatosis

Weekly phlebotomies will be allowed for carriers of the C282Y HFE mutation. --- C282Y ---

*Hemochromatosis, as defined by homozygosity for the C282Y HFE mutation or compound heterozygosity for C282Y/H63D mutations or Hepatic Iron Index ≥ 1.9. --- C282Y ---

Primary Outcomes

Measure: To determine in a 24 month controlled study whether iron depletion by phlebotomy improves insulin sensitivity, and thereby reduces hepatic steatosis and inflammation in subjects with nonalcoholic steatohepatitis

Time: 24 months

Secondary Outcomes

Measure: To assess the effect of iron depletion on glucose tolerance status. Glucose tolerance will be determined by OGTT in subjects without type 2 diabetes (T2D), and by HbA1c levels and the change in dosage of pharmacological therapy in those with T2D.

Time: 24 months

18 A Phase III, Randomized Study of the Effects of Parenteral Iron, Oral Iron, or No Iron Supplementation on the Erythropoietic Response to Darbepoetin Alfa for Cancer Patients With Chemotherapy-Associated Anemia

RATIONALE: Darbepoetin alfa may cause the body to make more red blood cells. Red blood cells contain iron that is needed to carry oxygen to the tissues. It is not yet known whether giving darbepoetin alfa (DA) together with intravenous iron or oral iron is more effective than giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy. PURPOSE: This randomized phase III trial is studying giving darbepoetin alfa together with iron to see how well it works compared with giving darbepoetin alfa together with a placebo in treating anemia caused by chemotherapy in patients with cancer.

NCT00661999 Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific Biological: darbepoetin alfa Dietary Supplement: ferrous sulfate Drug: sodium ferric gluconate complex in sucrose Other: placebo
MeSH:Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Precancerous Conditions Anemia Lymphoproliferative Disorders
HPO:Anemia Leukemia Lymphoma Lymphoproliferative disorder Multiple myeloma

DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Precancerous Conditions Anemia Lymphoproliferative Disorders OBJECTIVES: Primary * To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with chemotherapy-associated anemia. --- C282Y ---

DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months DISEASE CHARACTERISTICS: - Diagnosis of a non-myeloid cancer (other than non-melanomatous skin cancer) - Receiving or scheduled to receive chemotherapy (biological agents, such as small molecules/tyrosine kinase inhibitors and antibody-based therapies, are allowed) - Has chemotherapy-related anemia (hemoglobin < 11 g/dL) - No anemia known to be secondary to gastrointestinal bleeding or hemolysis - No anemia known to be secondary to vitamin B12 or folic acid deficiency + Vitamin B12 and folic acid deficiency must be ruled out if the mean corpuscular volume (MCV) is > 100 fL - No anemia secondary to chemotherapy-induced myelodysplastic syndromes - No primary hematologic disorder causing moderate to severe anemia (e.g., congenital dyserythropoietic anemia, homozygous hemoglobin S disease or compound heterozygous sickling states, or thalassemia major) - Carriers for these disease states are eligible - No first-degree relative with primary hemochromatosis (unless the patient has undergone HFE genotyping and was found to have at least one wild-type allele, while the proband in the family demonstrated to have either the common C282Y or H63D mutation) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Ferritin > 20 mcg/L (i.e., not obviously iron deficient) - ALT or AST < 5 times upper limit of normal - Alert, mentally competent, and able to sign informed consent - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - Willing or able to be randomized and undergo study treatment - Willing or able to fill out quality-of-life forms - No uncontrolled hypertension (i.e., systolic blood pressure [BP] ≥ 180 mm Hg or diastolic BP ≥ 100 mm Hg) - No history of uncontrolled cardiac arrhythmias - No pulmonary embolism or deep venous thrombosis within the past year (unless the patient is on anticoagulation therapy and planning to continue it during study participation) - No known hypersensitivity to darbepoetin alfa, erythropoietin, mammalian cell-derived products, iron, or human albumin - No seizures within the past 3 months - No gastrointestinal conditions expected to cause significant impairment of oral iron, such as untreated celiac disease or amyloidosis involving the gut - Patients with celiac disease who are adhering to a gluten-free diet are eligible PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 3 months since prior darbepoetin alfa, epoetin alfa, or any investigational forms of erythropoietin (e.g., gene-activated erythropoietin or novel erythropoiesis-stimulating protein) - More than 1 year since prior peripheral blood stem cell or bone marrow transplantation - More than 2 weeks since prior red blood cell transfusions - More than 14 days since prior major surgery - No prior gastrectomy or resection of > 100 cm of small intestine - Not planning to undergo stem cell or bone marrow transplantation within the next 6 months Anemia Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Precancerous Condition Unspecified Adult Solid Tumor, Protocol Specific Lymphoma Leukemia Multiple Myeloma Neoplasms, Plasma Cell Precancerous Conditions Anemia Lymphoproliferative Disorders OBJECTIVES: Primary * To compare the effects of IV iron, oral iron, or placebo in combination with darbepoetin alfa on the hematopoietic response rate, defined as a hemoglobin increment of ≥ 2.0 g/dL from baseline or achievement of hemoglobin of ≥ 11 g/dL in the absence of red blood cell transfusions (RBC) in the preceding 28 days of the treatment period, in cancer patients with chemotherapy-associated anemia. --- C282Y --- --- H63D --- --- C282Y ---

Primary Outcomes

Description: Hematopoietic response was defined as Hemoglobin (Hb) increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.

Measure: Hematopoietic Response Rate Defined as the Number of Participants Who Exhibit a Hematopoietic Response

Time: 16 Weeks

Secondary Outcomes

Measure: Percentage of Patients Maintaining an Average Hemoglobin Level Within the National Comprehensive Cancer Network (NCCN) Range (11-13 g/dL) Through Week 16, Once Achieving a Hemoglobin of ≥ 11 g/dL

Time: 16 Weeks

Measure: Incidence of Patients Receiving at Least One Red Blood Cell (RBC) Transfusions

Time: Week 1 to Week 16

Description: Value at 7 weeks minus value at baseline.

Measure: Mean Increment in Hemoglobin Level at Week 7

Time: Baseline and 7 weeks

Description: Value at 16 weeks minus value at baseline.

Measure: Mean Increment in Hemoglobin Level at Week 16

Time: Baseline and 16 weeks

Description: Hematopoietic response was defined as Hb increment of 2.0 g/dL from baseline or achievement of Hb >= 11 g/dL (whichever occurs first) in the absence of red blood cell transfusions during the preceding 28 days during the treatment period.

Measure: Time to Hematopoietic Response

Time: 16 weeks

Measure: Time to First Red Blood Cell (RBC) Transfusions

Time: 16 weeks

Description: Overall QOL item score range: 0 (Worst) to 10 (Best), ordinal. Change: score at 16 weeks minus score at baseline.

Measure: Change From Baseline in Overall Quality of Life (QOL) Score as Measured by the Linear Analogue Self Assessment (LASA)

Time: Baseline and 16 weeks

Description: SDS Scale range: 0 (Worst), 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.

Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by Symptom Distress Scale (SDS) at End of Study

Time: Baseline and 16 weeks

Description: Fatigue Now Scale range: 0 (No Fatigue) to 10 (Worst), ordinal. Change: score at 16 weeks minus score at baseline.

Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by Brief Fatigue Inventory(BFI) Fatigue Now Scale at End of Study

Time: Baseline and 16 weeks

Description: FACT-AN Scale range: 0 (Worst) to 100 (Best), ordinal. Change: score at 16 weeks minus score at baseline. A clinically significant result will be defined as a shift of 10 points on a 0-100 point transformed scale between the average QOL scores of the 3 variants of iron therapy.

Measure: Change From Baseline in Quality of Life (QOL) Score as Measured by The Functional Assessment of Cancer Therapy-Anemia (FACT-An) at End of Study

Time: Baseline and 16 weeks

Measure: C-reactive Protein (CRP) Level at Week 1, Week 7 and Week 16

Time: 1 Week, 7 Weeks and 16 Weeks

Measure: Soluble Transferrin Receptor (sTfR)Level at Week 1, Week 7 and Week 16

Time: 1 week, 7 weeks and 16 weeks

Measure: Ferritin Level at Baseline, Week 7 and Week 16

Time: Baseline, 7 weeks and 16 weeks

Description: MCV is a measure of the average red blood cell volume.

Measure: Mean Corpuscular Volume (MCV) Level at Baseline, Week 7 and Week 16

Time: Baseline, 7 weeks and 16 weeks

Measure: Transferrin Saturation at Baseline, Week 7 and Week 16

Time: Baseline, 7 weeks and 16 weeks

19 Effects of Intravenous Injection of Erythropoietin on Hepcidin Pharmacokinetics in Healthy Volunteers

The aim of this study is to measure the variations of serum and urinary hepcidin levels following a single intravenous injection of erythropoietin in healthy volunteers. Hepcidin is a major regulator of iron homeostasis. It acts by binding on ferroportin, and limits cellular efflux of iron through enterocytes and macrophages. Anemia and hypoxia are known to modulate hepcidin synthesis. In these situations, erythropoietin synthesis is increased, so it can be postulated that erythropoietin could modulate hepcidin synthesis.

NCT00687518 Iron Metabolism Disorders Drug: Erythropoietin Drug: Placebo
MeSH:Metabolic Diseases Iron Metabolism Disorders

Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Iron Metabolism Disorders Metabolic Diseases Iron Metabolism Disorders null --- C282Y ---

Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Inclusion Criteria: - healthy volunteers - male aged 18 - 30 - normal routine laboratory values - normal ECG - normal iron status Exclusion Criteria: - C282Y mutation of the HFE gene - alcohol or tobacco consumption Iron Metabolism Disorders Metabolic Diseases Iron Metabolism Disorders null --- C282Y --- --- C282Y ---

Primary Outcomes

Measure: serum hepcidin levels

Time: over 24 hours

Secondary Outcomes

Measure: urinary hepcidin levels

Time: over 24 hours

Measure: serum iron and ferritin levels

Time: over 24 hours

20 A Phase II Trial of the Safety and Efficacy of Iron Reduction by Phlebotomy in Recipients of Hematopoietic Stem Cell Transplants

Hypothesis: The reduction of total body iron by phlebotomy will be safe and feasible in the post-HSCT setting Iron overload is common after hematopoietic stem cell transplantation. It is associated with chronic liver disease, with increased rates of infection and decreased survival. Eligible, consenting patients will have once monthly phlebotomy procedures (500ml) for 12 months. SAFETY: At each visit, patients will have a comprehensive assessment prior to starting and after completing the phlebotomy. This assessment will include determination of pain at phlebotomy site, local infection and an assessment of symptoms of anemia including presyncope, fatigue and dyspnea. The patient's pulse, blood pressure, respiratory rate and temperature will also be determined before and following the phlebotomy. EFFICACY: Iron stores will be measured serially in each patient. Measurements will be performed prior to the start of phlebotomy, and at 6 months and 12 months following the start of the series of 12 phlebotomies. These evaluations will be undertaken regardless of the number of phlebotomies which the patient actually undergoes. Iron stores will be estimated by measuring serum ferritin and transferrin saturation levels. Total body iron will be estimated from hepatic and cardiac iron concentration as measured by magnetic resonance imaging (MRI). Gandon et al. (12) described a non-invasive technique using MRI to measure hepatic iron stores. Iron is a paramagnetic substance which causes local magnetic field inhomogeneities leading to dephasing and signal loss in MRI. Gradient echo sequences are most susceptible to their effects because they do not use a 180° refocusing pulse, unlike conventional spin-echo sequences. Gandon et al. used multiple gradient echo sequences, compared the signal in liver to adjacent muscle and used this ratio to correlate with hepatic iron levels measured on tissue biopsy samples using spectrophotometric analysis. Multiple sequences were used because the nomogram comparing the L/M signal ratio is linear over only a small concentration of tissue iron.

NCT00689182 Iron Overload Procedure: monthly phlebotomy x 12 months
MeSH:Iron Overload

Serum samples will also be collected at baseline to screen for the most common mutations of the HFE gene (C282Y mutation and H63D mutation) as hereditary hemochromatosis is common in the general population and may contribute to iron overload in HSCT recipients. --- C282Y ---

Primary Outcomes

Measure: Iron stores, total body iron

Time: 1 year

21 The Effect of the Dietary Supplement Protandim on Non-Alcoholic Steatohepatitis: A Randomized, Double Blind, Placebo-Controlled Study

The purpose of this study is to evaluate the effect of Protandim on the degree of liver injury after one year of supplementation. Protandim is a nutritional supplement composed of the following 5 botanical extracts: Bacopa Moniera extract, Milk Thistle extract, Ashwagandha powder, Green tea, and Turmeric extract. Protandim is commercially available and can be purchased without a prescription. Our findings could lead to a better understanding of the role of oxidative stress and antioxidant therapy in NASH and may ultimately help improve patient care. Hypothesis #1: Protandim will lead to a significant improvement in NAS compared to placebo. Hypothesis #2: Protandim will lead to a significant decrease in serum markers of oxidative stress and liver chemistry tests. Hypothesis #3: Protandim will lead to decreased levels of TNF- α compared to placebo.

NCT00977730 Non-Alcoholic Steatohepatitis Dietary Supplement: Protandim Dietary Supplement: Placebo
MeSH:Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Hepatic steatosis

7. Iron overload/hemochromatosis, as defined by the following: elevated transferrin saturation (greater than 45 percent) OR serum ferritin (> 300 microg/L in men or >200 microg/L in women), with one of the following: 1) presence of 3+ or 4+ stainable iron on liver biopsy (if obtained); or 2) Hemochromatosis gene testing showing homozygosity for C282Y or compound heterozygosity for C282Y/H63D (if obtained). --- C282Y ---

Primary Outcomes

Measure: Change in NAS at study completion in the Protandim group compared to the placebo group.

Time: 12 months

22 Impact of Host Iron Status and Iron Supplement Use on Growth and Viability of the Erythrocytic Stage of Plasmodium Falciparum

The purpose of this study is to perform laboratory based studies to determine if the growth and development of the malaria parasite is effected by iron status of its host (the person infected with the malaria parasite). Iron deficiency affects over 500 million people including many pregnant women and children from areas of the world that are plagued by malaria. Some population based studies have suggested that iron deficiency protects people from getting malaria and this has raised questions about the wisdom of public health policies that provide universal iron supplementation in countries where malaria is common. We will use red blood cells and sera from patients with iron deficiency anemia, hereditary hemochromatosis and normal individuals who are taking iron supplements to look at this question in a very systematic way. This study should provide information for or against a possible mechanism by which iron deficiency may affect the malaria parasite. The results will contribute to efforts to develop evidence-based public health policies on iron supplementation policies in malaria-endemic areas. There are three different types of individuals involved in this study (1) people with iron deficiency anemia who will be taking iron supplementation (2) people without iron deficiency anemia who will be taking iron supplementation and (3) people with a condition called hereditary hemochromatosis who have an excess of iron in their bodies.

NCT01027663 Iron Deficiency Anemia Malaria Dietary Supplement: Iron Supplement
MeSH:Malaria Anemia, Iron-Deficiency
HPO:Iron deficiency anemia

From the genotype standpoint, only patients homozygous for the C282Y and H63D mutations and those that are compound heterozygotes for C282Y/H63D will be enrolled. --- C282Y ---


23 Prospective Randomized Study Comparing the Effect of Phlebotomy and Lifestyle and Diet Advices vs Lifestyle and Diet Advices Only on Glycemia in Patients With Dysmetabolic Liversiderosis

Insulin resistance-associated hepatic iron overload (IR-HIO), also defined as dysmetabolic iron overload syndrome or dysmetabolic liversiderosis, is a common cause or iron overload in France, mainly in middle-age patients with increased serum ferritin levels associated with normal serum transferrin saturation, and normal serum iron concentration in the absence of other known cause of increased serum ferritin levels. Treatment includes a combination of dietary measures and physical activity to correct metabolic disorders. Phlebotomies seem to be beneficial when serum ferritin level is high. This study aims at comparing the effect of iron depletion (by phlebotomy) plus lifestyle and diet advices versus lifestyle and diet advices alone on blood glucose level and insulin sensitivity in subjects with IR-HIO in order to assess the benefits of phlebotomies on the reduction of risk of diabetes and cardiovascular associated complications.

NCT01045525 Liver Cirrhosis Iron Overload Procedure: Phlebotomy Behavioral: Lifestyle and diet advices
MeSH:Liver Cirrhosis Iron Overload
HPO:Cirrhosis Hepatic fibrosis

Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Liver Cirrhosis Iron Overload Liver Cirrhosis Iron Overload Non applicable --- C282Y ---

Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Inclusion Criteria: - Age over 18 - Signed written informed consent - Ferritin ≥ 450 µg/L and ≤ 1500 µg/L - Hepatic iron overload proved by MRI or histological biochemical measurement (Iron hepatic concentration ≥ 50 μmol/g) - At least one of the following criteria : - Body mass index > 25 kg/m² - Systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90 mmHg or antihypertensive treatment - Abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women) - Fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment - Fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment - Fasting blood glycemia ≥ 5.6 mmol/L Exclusion Criteria: - Subjects deprived of their liberty by judicial or administrative decision - Pregnant women - Other causes of increased serum ferritin levels: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyper-hemolysis - Alcohol consumption more than 210 g for men and 140 g for women per week within the year before inclusion - Haemochromatosis established by the C282Y homozygous genotype - Chronic hepatic cytolysis due to : viral infection (HBV, HCV), alcohol, hyperthyroid disease, celiac disease, drug or immune hepatitis - Increased serum ferritin levels - cataract syndrome (familial cataract or personal history of cataract before 50 years of age) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Contraindication of phlebotomy - Haemoglobin <13 g/dL for men and <12g/dL for women (threshold established by the French Blood Agency) - Congestive heart failure or coronary heart disease - Hepatic failure (TP<60%), renal failure (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Fasting blood glycemia > 7 mmol/L or type 1 or type 2 diabetes, treated or not - Use of drugs known to have anti-steatotic effects : metformin, thiazolidinedione Liver Cirrhosis Iron Overload Liver Cirrhosis Iron Overload Non applicable --- C282Y --- --- C282Y ---

Primary Outcomes

Measure: Fasting blood glycemia (T0 of Oral Glucose Tolerance Test)

Time: 12 months

Secondary Outcomes

Measure: Rate of Body mass index > 25 kg/m²

Time: 12 months

Measure: Rate of systolic blood pressure ≥ 130mmHg or diastolic blood pressure ≥ 85 mmHg or antihypertensive treatment

Time: 12 months

Measure: Rate of abdominal obesity (waist measurement ≥ 94 cm for men and ≥ 80 cm for women)

Time: 12 months

Measure: Rate of fasting triglyceridemia ≥ 1.7 mmol/L or triglyceride-lowering treatment

Time: 12 months

Measure: Rate of fasting HDL cholesterol < 1.03 mmol/L for men and < 1.29 mmol/L for women or HDL cholesterol-elevating treatment

Time: 12 months

Measure: Rate of fasting glycemia ≥ 5.6 mmol/L

Time: 12 months

Measure: HbA1c value

Time: 12 months

Measure: Quality of life estimated with SF36 form and tolerance to treatment

Time: 12 months

Measure: Insulinoresistance indexes calculated at T0 and T30 min of Oral Glucose Tolerance Test (OGTT)

Time: 12 months

Measure: Biological markers: CRP, hyaluronic acid, fibrometer

Time: 12 months

Description: Two dimensional (2D) speckle tracking echocardiography (STE)

Measure: myocardial deformation

Time: 12 months

24 Effects of Blood Letting on Insulin Sensitivity and Blood Pressure in Patients With Metabolic Syndrome: A Randomized Controlled Trial

Metabolic syndrome (MS) has an increasing prevalence worldwide and there is an urgent need for improvement of medical treatment. In traditional medicine phlebotomy (blood letting) is a recommended treatment for subjects with obesity and vascular disease. Recent studies showed that blood letting with iron depletion may improve insulin sensitivity in patients with diabetes mellitus. The investigators aimed to test if traditional blood letting has beneficial effects in patients with MS. A randomized trial with a sample size of 64 self-referred MS patients was conducted. Patients in the blood letting group were allocated to blood letting intervention and the control group was offered a later treatment (waiting list). In the intervention group 300-400 ml of venous blood were withdrawn at day 1 and after 4 weeks. Primary outcomes were the change of systolic blood pressure and of insulin sensitivity as measured by HOMA-Index.

NCT01328210 Metabolic Syndrome Procedure: blood letting
MeSH:Metabolic Syndrome Syndrome

Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Metabolic Syndrome Metabolic Syndrome Syndrome null --- Cys282Tyr ---

Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Inclusion Criteria: - 25-70 years of age - given diagnosis of metabolic syndrome Exclusion Criteria: - clinically significant hepatic, neurological, endocrinologic, or other major systemic or inflammatory disease, including malignancy - known history of hemochromatosis, or presence of the Cys282Tyr mutation - history of drug or alcohol abuse - manifest cardiac disease - history of disturbances in iron balance (e.g., hemosiderosis from any cause, atransferrinemia) - preexisting anemia Metabolic Syndrome Metabolic Syndrome Syndrome null --- Cys282Tyr --- --- Cys282Tyr ---

Primary Outcomes

Description: Glucose and insulin are measured on the basis of overnight fasting blood samples and Insulin sensitivity calculated according to HOMA-Index

Measure: insulin sensitivity

Time: change from baseline at 6 weeks

Description: Blood pressure is measured twice after 5 minutes rest in the sitting position by sphygmomanometry

Measure: systolic blood pressure

Time: change from baseline at 6 weeks

Secondary Outcomes

Measure: diastolic blood pressure

Time: change from baseline at 6 weeks

Measure: HbA1c

Time: change from baseline at 6 weeks

Measure: blood lipids

Time: change from baseline at 6 weeks

Measure: serum ferritin

Time: change from baseline at 6 weeks

Measure: adiponectin

Time: change from baseline at 6 weeks

Measure: blood count

Time: change from baseline at 6 weeks

Measure: serum iron

Time: change from baseline at 6 weeks

Measure: hs-CRP

Time: change from baseline at 6 weeks

Measure: pulse rate

Time: change from baseline at 6 weeks

Measure: serum glucose

Time: change from baseline at 6 weeks

25 Erythrocytapheresis Versus Phlebotomy as Maintenance Therapy in Patients With Hereditary Hemochromatosis; a Randomised, Single Blinded Sequential, Cross-over Trial

Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism, resulting in excessive iron overload. Phlebotomy is currently the standard therapy. More recently Therapeutic Erythrocytapheresis (TE) has become a new therapeutic modality, which potentially offers a more efficient method to remove iron overload with fewer procedures.In the proposed clinical trial the investigators will examine whether TE can keep the ferritin levels in patients requiring maintenance therapy below 50 microg/L, with minimally half the number of treatment procedures when compared to current standard therapy by P.

NCT01398644 Hereditary Hemochromatosis Other: Phlebotomy and erythrocytapheresis
MeSH:Hemochromatosis

Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Hereditary Hemochromatosis Hemochromatosis The research population exists of patients with HH ( by genetic analysis confirmed as homozygous for C282Y) living in south-east of the Netherlands and currently treated with phlebotomy as maintenance treatment to keep their serum ferritin levels < 50 ug/l. --- C282Y ---

Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Hereditary Hemochromatosis Hemochromatosis The research population exists of patients with HH ( by genetic analysis confirmed as homozygous for C282Y) living in south-east of the Netherlands and currently treated with phlebotomy as maintenance treatment to keep their serum ferritin levels < 50 ug/l. --- C282Y --- --- C282Y ---

Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Inclusion Criteria: - homozygous for C282Y - currently treated with phlebotomy as maintenance therapy for at least 6 month - ferritin level between 30-50 micog/L - age 18 years an older - weight more than 50 kg - signed informed consent - willingness to fill out additional questionnaires at three points in time Exclusion Criteria: - chelating therapy - forced dietary regime - aged below 18 years - excessive overweight ( BMI more than 35) - pregnancy Hereditary Hemochromatosis Hemochromatosis The research population exists of patients with HH ( by genetic analysis confirmed as homozygous for C282Y) living in south-east of the Netherlands and currently treated with phlebotomy as maintenance treatment to keep their serum ferritin levels < 50 ug/l. --- C282Y --- --- C282Y --- --- C282Y ---

Primary Outcomes

Measure: The difference in number of required treatments and the interval between treatments per year to keep the serum ferritin levels between 30-50 microg/L

Time: one year after first phlebotomy treatment and one year after first erythrocytapheresis treatment

26 Effect of Curcumin on Iron Metabolism in Healthy Volunteer

The purpose of this study is to determine the impact of curcumin, administrated orally, on iron metabolism in healthy volunteers. Iron metabolism will be describe by hepcidin expression that the investigators observed in vitro and serum hepcidin levels.

NCT01489592 Healthy Volunteers Drug: curcuma longa

In vitro: the coculture model that we previously developed to analyze endogenous hepcidin expression, and human hepatic cells line (HepG2) stimulated or not by IL-6 which governs the STAT3 pathway, transfected with gene reporter constructs containing hepcidin promoter.. Inclusion Criteria: - Body mass index between 18 et 25 Kg/m² - Non smoker - No swallowing disorders - Normal clinical exam - Normal ECG - Normal values for routine biological tests : serum iron, transferrin saturation,, hemogram ferritin, C Reactive Protein, AST, ALT, HDL and LDL cholesterol, triglycerides - No C282Y mutation within the HFE gene - Affiliation to social security - Written informed consent obtained Exclusion Criteria: - Chronic or evolutive disease - Infection during the 7 days before each sequence - Drug or alcohol (>30g) abuse - Current treatment - Known food allergy - stay at altitude (> 1500m) in 2 months - Positive serology for hepatitis B or C virus or HIV. - Transfusion or blood donation during the last three months. --- C282Y ---

Inclusion Criteria: - Body mass index between 18 et 25 Kg/m² - Non smoker - No swallowing disorders - Normal clinical exam - Normal ECG - Normal values for routine biological tests : serum iron, transferrin saturation,, hemogram ferritin, C Reactive Protein, AST, ALT, HDL and LDL cholesterol, triglycerides - No C282Y mutation within the HFE gene - Affiliation to social security - Written informed consent obtained Exclusion Criteria: - Chronic or evolutive disease - Infection during the 7 days before each sequence - Drug or alcohol (>30g) abuse - Current treatment - Known food allergy - stay at altitude (> 1500m) in 2 months - Positive serology for hepatitis B or C virus or HIV. - Transfusion or blood donation during the last three months. --- C282Y ---

Primary Outcomes

Measure: Maximal variation of serum hepcidin level after oral administration of curcumin

Time: within 48 hours after administration of curcumin

Secondary Outcomes

Description: Iron, ferritin, transferrin, transferrin saturation

Measure: Plasmatic iron bioavailability

Time: 30min, 1H, 2H, 3H, 4H, 6H, 8H, 12H, 24H et 48H

Description: In vitro: the coculture model that we previously developed to analyze endogenous hepcidin expression, and human hepatic cells line (HepG2) stimulated or not by IL-6 which governs the STAT3 pathway, transfected with gene reporter constructs containing hepcidin promoter.

Measure: Evaluation of the inhibitory activity of volunteers's serum on hepcidin expression by hepatocytes

Time: 30min, 1h, 2h, 3h, 4h, 6h, 8h, 12h, 24h

27 Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis

Hereditary Hemochromatosis (HH) is a genetic disorder of iron metabolism, resulting in excessive iron overload causing damage of different important organs like heart, liver, pancreas and joints. Complications and symptoms can regress by intensive treatment reducing the iron overload stores.Different genes have been identified playing a role in the pathophysiology of iron overload. A clinically important HFE gene mutation is the C282Y, located on chromosome 6. Phlebotomy is currently the standard therapy which consists of removal of 500 ml whole blood weekly, representing a loss of 250 mg iron. In naive patients between 20 to 100 phlebotomies are required to reduce the serum ferritine levels to 50 μg/L. Thereafter, a lifelong maintenance therapy of 3 to 6 phlebotomies yearly is needed. For absorption, dietary iron ( 70%) is reduced by gastric acid form the ferric (Fe3+) to the ferrous form (Fe2+). Recently, in an observational open study, Hutchinson et al. found that HH patients treated with proton pump inhibitors (PPI) needed fewer phlebotomies, resulting in a drop of 2.5 (SEM 0.25) to 0.5 (SEM 0.25) liter per year. Research question: The primary objective is to determine the effectiveness and cost effectiveness of PPI's compared to standard phlebotomy therapy in the prevention of iron overload in HH patients. Multi-center trial in two hospitals in the South of Limburg (Atrium medical Center, Maastricht university medical center ) and hospital in Belgium (University Hospital Gasthuisberg). The study will be conducted in randomised double blind manner. The follow up will be one year. Patients are randomized either for the group receiving a PPI or a placebo. Every 2 month the ferritin level is measured and decided if the patient need a phlebotomy (Ferritin >100 µg/L).

NCT01524757 Hemochromatosis Drug: Pantoprazole
MeSH:Hemochromatosis

A clinically important HFE gene mutation is the C282Y, located on chromosome 6. --- C282Y ---

Inclusion Criteria: - Patients with hereditary hemochromatosis (HH), homozygous for C282Y, currently treated with phlebotomy as maintenance therapy for at least 12 months with ≥ 3 phlebotomies per year. --- C282Y ---

Primary Outcomes

Measure: the total number of phlebotomies for the group taking PPI treatment compared to the group taking placebo will be the primary endpoint of the study.

Time: 12 months

Secondary Outcomes

Measure: number of participants with side effects

Time: 12 months

28 Clinical, Biological, Genetic and Functional Characterization of Rare Iron Overload Phenotypes Associated With Hepcidin Deficiency Except C282Y Homozygosity.

Chronic iron overload is responsible for morbidity and mortality. There are many genetic and acquired causes. One of them is an hepcidin deficiency. Hepcidin is the regulating hormone for iron. The study explores this specific cause, and aim to characterize this iron overload in term of clinical, biological, genetic and functional specificities.

NCT01541813 Rare Iron Overloads Except C282Y Homozygosity
MeSH:Iron Overload

Clinical, Biological, Genetic and Functional Characterization of Rare Iron Overload Phenotypes Associated With Hepcidin Deficiency Except C282Y Homozygosity.. Rare Iron Overloads Except C282Y Homozygosity : Description and Characterization. --- C282Y ---

Clinical, Biological, Genetic and Functional Characterization of Rare Iron Overload Phenotypes Associated With Hepcidin Deficiency Except C282Y Homozygosity.. Rare Iron Overloads Except C282Y Homozygosity : Description and Characterization. --- C282Y --- --- C282Y ---

Non inclusion criteria: - HFE hemochromatosis: C282Y/C282Y homozygosity - Treatment by iterative phlebotomies (more than 2 phlebotomies) - Hematological diseases with dyserythropoiesis and/or repeated transfusions - Low haptoglobin level, suggesting chronic hemolysis or myelodysplasia - Long-term iron oral and/or parenteral supplementation Inclusion criteria: - Biological profile suggesting hepcidin deficiency: - high serum iron (> 25μmol / l) checked at least 2 times. --- C282Y ---

Non inclusion criteria: - HFE hemochromatosis: C282Y/C282Y homozygosity - Treatment by iterative phlebotomies (more than 2 phlebotomies) - Hematological diseases with dyserythropoiesis and/or repeated transfusions - Low haptoglobin level, suggesting chronic hemolysis or myelodysplasia - Long-term iron oral and/or parenteral supplementation Rare Iron Overloads Except C282Y Homozygosity Iron Overload One of chronic iron overload profiles is a deficit in hepcidin. --- C282Y ---

Non inclusion criteria: - HFE hemochromatosis: C282Y/C282Y homozygosity - Treatment by iterative phlebotomies (more than 2 phlebotomies) - Hematological diseases with dyserythropoiesis and/or repeated transfusions - Low haptoglobin level, suggesting chronic hemolysis or myelodysplasia - Long-term iron oral and/or parenteral supplementation Rare Iron Overloads Except C282Y Homozygosity Iron Overload One of chronic iron overload profiles is a deficit in hepcidin. --- C282Y --- --- C282Y ---

The main objective of this study is the clinical, biological, genetic and functional characterization of rare iron overload phenotypes associated with hepcidin deficiency except C282Y homozygosity. --- C282Y ---


29 Effects of Phlebotomy on Insulin Sensitivity in Insulin Resistance-associated Hepatic Iron Overload Patients

The purpose of this study is to evaluate efficacy of phlebotomy on insulin sensitivity as evaluated by euglycemic-hyperinsulinic clamp in insulin resistance-associated hepatic iron overload patients.

NCT01572818 Insulin Resistance Iron Overload Procedure: phlebotomy Behavioral: dietary and lifestyle counseling
MeSH:Insulin Resistance Iron Overload
HPO:Insulin resistance

Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Insulin Resistance Iron Overload Insulin Resistance Iron Overload The main objective of this study is to evaluate in patients with HSD effects of treatment with phlebotomy rules with lifestyle and dietary rules versus lifestyle modifications alone on peripheral insulin resistance (assessed by hyperinsulinemic clamp). --- C282Y ---

Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Inclusion Criteria: - Age between 18 and 70 years - Ferritin between 450 and 1000 µg/L - Hepatic iron overload proved by MRI (CHF >36 µmol/g) - Body mass index > 25 kg/m² - Fasting glycemia <1,26 g/L - HbA1c < 6,5% - Signed written and informed consent Exclusion Criteria: - Other causes of hyperferritinemia: - Inflammatory syndrome (CRP >10 mg/L) or inflammatory, immune or malignant diseases - Hyperferritinemia-cataract syndrome (familial cataract or personal history of cataract before 50 years old) - Low ceruloplasmin level - Porphyria (cutaneous signs) - Haemochromatosis established by the genotype (C282Y homozygous or C282Y/H63D coumpound heterozygous genotypes) - Contraindication of phlebotomy - Haemoglobin <13,5 g/dL (threshold established by the Etablissement Français du Sang) - Heart failure or coronary heart diseases - Hepatic failure, renal (GFR <50mL/min) or respiratory insufficiency (chronic dyspnea) - Poor venous system - Viral, immune, genetic, vascular, malignant or toxic chronic hepatic disease - Alcohol consumption more than 21 doses per week during 5 years or more - Type 1 or type 2 diabetes - Oral anti-diabetic, corticoids or immune suppressor drugs - Hepatic severe disease - Claustrophobia, having a pace-maker or intracerebral clips - Subjects deprived of their liberty by judicial or administrative decision, subjects that are not affiliated to social security or topics exclusion period of a previous study Insulin Resistance Iron Overload Insulin Resistance Iron Overload The main objective of this study is to evaluate in patients with HSD effects of treatment with phlebotomy rules with lifestyle and dietary rules versus lifestyle modifications alone on peripheral insulin resistance (assessed by hyperinsulinemic clamp). --- C282Y --- --- H63D --- --- C282Y ---

Primary Outcomes

Measure: Glucose Infusion Rate by euglycemic-hyperinsulinic clamp

Time: 6 months

Secondary Outcomes

Measure: hepatic parameters

Time: 6 months

Description: IL-6, TNF alpha, CRP

Measure: inflammation markers

Time: 6 months

Description: adiponectin, PAI1, leptin

Measure: Adipokins markers

Time: 6 months

Measure: SHBG

Time: 6 months

Measure: HOMA-IR

Time: 6 months

Description: transaminase (ALT, AST), gamma GT

Measure: Hepatic iron overload (MRI)

Time: 6 months

Measure: Abdominal and sub-cutaneous fat surface (MRI)

Time: 6 months

Description: serum iron, ferritin, saturation of transferrin

Measure: iron parameters

Time: at 6 months

Description: HDL-c, LDL-c, triglycerides

Measure: lipid profile

Time: at 6 months

30 Mi-Iron - Moderately Increased Iron - is Reducing Iron Overload Necessary?

Haemochromatosis is a preventable genetic iron overload disorder. Untreated, it can shorten life due mainly to liver cirrhosis and cancer. It can be prevented by blood donation to maintain normal iron levels. It is unclear, however, whether treatment is necessary when individuals have moderate elevation of iron in the body. This research project will study the effects of treatment in this group by assessing a number of scans, questionnaires and blood tests in treated and untreated individuals.

NCT01631708 Hereditary Haemochromatosis Procedure: Erythrocytapheresis Procedure: Plasmapheresis
MeSH:Hemochromatosis Iron Overload

To assess oxidative stress, we will measure F2-isoprostanes, a validated marker of cellular lipid oxidative damage, in urine and blood.. Inclusion Criteria: 1. HFE C282Y homozygous. --- C282Y ---

Exclusion Criteria: 1. HH due to genotypes other than HFE C282Y homozygosity. --- C282Y ---

Inclusion Criteria: 1. HFE C282Y homozygous. --- C282Y ---

Primary Outcomes

Description: Modified Fatigue Impact Scale (MFIS). The MFIS is a shortened version of the Fatigue Impact Scale. This 21-item scale can be self completed and measures the impact of fatigue on physical, cognitive and psychosocial functioning. Each item is scored from 0 (never) to 4 (almost always) resulting in a score from 0-84. In addition, physical (0-36), cognitive (0-40) and psychosocial (0-8) subscale scores can be derived.

Measure: Fatigue

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have approximately 6 third weekly treatments however this will vary depending on initial SF.

Secondary Outcomes

Description: Liver fibrosis will be assessed using Hepascore and Fibrometer (blood tests) and transient elastography (ultrasound).

Measure: Change in markers of liver fibrosis

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).

Description: Medical Outcomes Study 36-item short form (SF36). As there are no specific quality of life tools available for HH, we will use this very widely used generic tool that has been used in a number of HH studies. This tool covers eight dimensions of health and wellbeing. One study found that individuals seen in a HH clinic and who had no clinical symptoms had significantly lower scores on a number of dimensions of the SF36 compared to population norms.

Measure: Quality of life

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).

Description: The Hospital Anxiety and Depression Scale (HADS) is a brief self-report measure designed to screen for anxiety symptoms and depression symptoms in a hospital setting. It is composed of two seven-item subscales, the Anxiety (HADS-A) and Depression (HADS-D) subscales, and a 14-item total scale (HADS-T). Participants use a four-point Likert-type scale to rate how they have felt in the past week. It has been found to be valid and reliable in various populations.

Measure: Depression and Anxiety

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).

Description: The presence and impact of arthritis will be measured by the Arthritis Impact Measurement Scales 2 short form. This is a 24 item validated scale that assesses the impact of arthritis on the individual over the past four weeks. We will also ascertain the use of arthritis medication at baseline and end of erythrocytapheresis/sham erythrocytapheresis.

Measure: Arthritis

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).

Description: To assess oxidative stress, we will measure F2-isoprostanes, a validated marker of cellular lipid oxidative damage, in urine and blood.

Measure: Markers of oxidative stress

Time: Clinically and statistically significant change in measures taken at baseline and at the end of treatment will be compared. Patients will have on average 6 third weekly treatments (15 weeks).

31 Ezetimibe Versus Placebo in the Treatment of Non-alcoholic Steatohepatitis

The purpose of the study is to see if the drug ezetimibe is a potential treatment for Nonalcoholic Steatohepatitis(NASH).

NCT01766713 Non Alcoholic Steatohepatitis Drug: Ezetimibe
MeSH:Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Hepatic steatosis

7. Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Primary Outcomes

Measure: Change in Liver Fat as Measured by MRI-PDFF

Time: Baseline, 24 weeks

32 HEPFER-Evaluation of a New Phenotypic Biological Marker in Genetic Type 1 Hemochromatosis

HFE(High iron FE)-related hereditary hemochromatosis has a highly variable penetrance. No phenotypic or genetic markers can predict the disease. The Iron Reabsorption Index (IRI), recently described by our group, correspond to the daily reabsorbed iron for a subject whose iron stock is stable and less than 50 µg / L. The IRI is constant over time, reflecting the importance of the underlying functional deficit. Hepcidin / ferritin (H / F) ratio may be an independent and constant over time marker of disease stage.No data are available on the validated values of this ratio. The goal of this project is to determine the intra-individual variations of the H / F ratio over time during maintenance therapy and to assess the correlation with the IRI.

NCT01784939 Hereditary Hemochromatosis C282Y Homozygous
MeSH:Hemochromatosis

Inclusion Criteria: - Men, at least 18 years old - hereditary hemochromatosis C282Y homozygous diagnosed and followed in the service of Liver Diseases, University Hospital of Rennes - Maintenance therapy with phlebotomy for at least 1 year with stable iron stock on the basis of at least four previous plasma ferritin < 50μg / L, - Written, free and informed consent Exclusion Criteria: - Intercurrent illness unrelated to hemochromatosis causing cytolysis or inflammatory reaction. --- C282Y ---

- Person with a measure of legal protection (guardianship) Inclusion Criteria: - Men, at least 18 years old - hereditary hemochromatosis C282Y homozygous diagnosed and followed in the service of Liver Diseases, University Hospital of Rennes - Maintenance therapy with phlebotomy for at least 1 year with stable iron stock on the basis of at least four previous plasma ferritin < 50μg / L, - Written, free and informed consent Exclusion Criteria: - Intercurrent illness unrelated to hemochromatosis causing cytolysis or inflammatory reaction. --- C282Y ---

- Person with a measure of legal protection (guardianship) Hereditary Hemochromatosis C282Y Homozygous Hemochromatosis HFE-related hereditary hemochromatosis has a highly variable penetrance : 1% of homozygous women and 30% of homozygous men would develop a clinically expressed disease. --- C282Y ---

The study involve 30 C282Y homozygous men, followed in a reference center with phlebotomy maintenance therapy and stabilized at a low level of ferritin (<50 µg / L) for at least 1 year. --- C282Y ---

Primary Outcomes

Description: values of Hepcidin / ferritin plasma ratio

Measure: distribution of values of Hepcidin / ferritin plasma ratio

Time: First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time

Secondary Outcomes

Measure: Correlation between Hepcidin / ferritin plasma ratio and IRI.

Time: First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time

Measure: Correlation between Hepcidin / Ferritin ratio before and after treatment

Time: First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time

Measure: Distribution of inter-individual Hepcidin / Ferritin ratio according to the stage of liver fibrosis

Time: First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time

33 Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis: Pathophysiological and Clinical Implications. Pilot Study.

Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). For the half of these predisposed subjects, the phenotypic expression of the disease needs a treatment. This treatment is based upon repeated bloodletting which is generally considered as simple, safe and effective. Nevertheless, it is still questioned as regard its physiopathological justification and its clinical implications. Indeed, bloodletting could cause an increase of non-transferrin bound iron (NTBI) particularly for its reactive form called labile plasma iron (LPI) This adverse physiopathological effect could have clinical consequences and could be linked with articular consequences which can be aggravated by the treatment.

NCT01810965 Hemochromatosis Type 1 Procedure: First evaluation phase : no intervention / Second evaluation phase: bloodletting of 7 ml/kg (with a maximum of 500ml)
MeSH:Hemochromatosis

Pilot Study.. Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y ---

Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Hemochromatosis Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y ---

Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Hemochromatosis Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y --- --- C282Y ---

Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Inclusion Criteria: - Men - Age 18 years or older - Homozygosity for the C282Y mutation of the HFE gene - With an indication of treatment by bloodletting (in accordance with the French HAS guidelines) - Ferritinemia ≥ 500µg/L - Transferrin saturation ≥ 75% - Never treated by bloodletting - Written informed consent Exclusion Criteria: - Contraindication to bloodletting - Chronic inflammatory or dysmetabolic or neoplastic disease - Major cardiovascular disease - Excessive consumption of alcohol (≥ 3gr/day) - Treatment by iron chelators, C or E vitamins - Stay in altitude> 1500m in the month preceding the period Day 1 - Patients under guardianship - Blood donation in the 3 past months - Night / shift workers Hemochromatosis Type 1 Hemochromatosis Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France). --- C282Y --- --- C282Y --- --- C282Y ---

Primary Outcomes

Measure: Maximal variation (delta maximum) of NTBI during the 5 days following a bloodletting

Time: Day 5

Secondary Outcomes

Measure: Kinetic of NTBI plasmatic concentration during the 5 days following a bloodletting

Time: Day 5

Measure: Maximal variation (delta maximum) of LPI during the 5 days following a bloodletting

Time: Day 5

Measure: Maximal variation (delta maximum) of hepcidin during the 5 days following a bloodletting

Time: Day 5

Measure: Kinetic of LPI plasmatic concentration during the 5 days following a bloodletting

Time: Day 5

Measure: Kinetic of hepcidin plasmatic concentration during the 5 days following a bloodletting

Time: Day 5

Measure: CRP

Time: Day 9, day 10, day 11 and day 12

Measure: Hemoglobin

Time: Day 9, day 10, day 11 and day 12

Measure: Soluble transferrin receptor

Time: Day 9, day 10, day 11 and day 12

Measure: EPO

Time: Day 9, day 10, day 11 and day 12

Measure: Circadian kinetic of NTBI plasmatic concentration when no bloodletting is performed

Time: Day 1

Measure: Circadian kinetic of API plasmatic concentration when no bloodletting is performed

Time: Day 1

Measure: Circadian kinetic of hepcidine plasmatic concentration when no bloodletting is performed

Time: Day 1

Measure: Maximal variation (delta maximum) of transferrin saturation during the 5 days following a bloodletting

Time: Day 5

Measure: Kinetic of transferrin saturation during the 5 days following a bloodletting

Time: Day 5

34 Deferasirox Versus Venesection in Patients With Hemochromatosis and for Treatment of Transfusional Siderosis in Myelodysplastic Syndrome: Diagnostics and New Biomarkers.

Hypothesis: Deferasirox can be used as a therapeutic agent to deplete the liver, heart and bone marrow of excess iron in patients with iron overload caused by myelodysplastic syndrome (MDS) and hemochromatosis (HC. Assess the effect of new serum biomarkers (NTBI and hepcidin) and MRI as indicators of iron overload and their usefulness to monitor iron depletion treatment. Study the effect of iron overload and iron depletion on intracellular signal transduction, trace metals concentrations in serum and urine and markers of oxidative stress in blood cells and urine.

NCT01892644 Hemochromatosis Myelodysplastic Syndromes Drug: Deferasirox Other: Venesection Drug: Deferasirox
MeSH:Preleukemia Myelodyspla Myelodysplastic Syndromes Hemochromatosis Iron Overload Syndrome
HPO:Myelodysplasia

Inclusion Criteria: - Patients with hemochromatosis, aged > 30 years, C282Y- homozygote, with serum-ferritin =/> 1000 µg/L - Patients aged > 18 years with verified low-risk or intermediate-1 risk of myelodysplastic syndrome, with normal cytogenetics and serum-ferritin > 1500 µg/L, or with a transfusion history of =/> red- blood-cell-transfusions. Exclusion Criteria: - Previous or current venesection - MDS patients eligible for hematopoietic stem cell transplantation - Subject complies with one or more of the following standard exclusion criteria for MRI examination; - If the patient has a pacemaker. --- C282Y ---

The most common are the classic C282Y and H63D point mutations of the hemochromatosis protein HFE, which disturbs its interaction with the transferrin receptor 1, the first step in the hepcidin signal cascade. --- C282Y ---

Homozygosity for C282Y is the strongest risk factor for serious iron overload and disease which develops after a long-lasting, asymptomatic period. --- C282Y ---

The study by Phatak et al (2010) was the first clinical trial to demonstrate the safety and efficacy of deferasirox in patients with C282Y-homzygot hemochromatosis. --- C282Y ---

Primary Outcomes

Measure: Changes from baseline in liver iron concentration (LIC) and heart iron concentration (HIC) determined by Magnetic Resonance Imaging (MRI), and in bone marrow iron content determined by microscopy after treatment with deferasirox.

Time: 0, 6 and 12 months

Secondary Outcomes

Measure: Change of hepcidin concentration in serum

Time: 0, 6 and 12 months

Measure: Change of non-transferrin bound iron (NTBI) concentration in serum

Time: 0, 6 and 12 months

Measure: Change of multiple trace metals in serum

Time: 0, 6 and 12 months

Measure: Change of intracellular signal molecules, mTOR, NFkB and stress sensor p53 in blood cells

Time: 0, 6 and 12 months

Description: Marker of oxidative DNA damage

Measure: Change of 8-oxodG in urine

Time: 0, 6 and 12 months

Description: Cu,Zn-Super Oxid Dismutase (SOD)is an antioxidant enzyme

Measure: Change of Cu,Zn-SOD activity in erythrocyte hemolysate

Time: 0, 6 and 12 months

Description: Serum analysis

Measure: Clinical chemistry: Na, K, Ca, Creatinine, creatinine kinase, CRP, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GT), lactate dehydrogenase (LD), albumin, bilirubin.

Time: 0, 2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks posttreatment

Description: Morning spot urine sample.

Measure: Urine routine test strip for detection of blood, protein, and nitrite

Time: 0,2,4,6,8 weeks and 3,4,5,6,7,8,9,10,11,12 months

Measure: Ferritin concentration in serum

Time: 0,2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks post treatment

Measure: Transferrin saturation in serum

Time: 0,2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks post treatment

Measure: HbA1c

Time: 0, 2,6,12 months

Measure: INR ( International normalized ratio)

Time: 0,2,6,12 months

Measure: Analysis of hemoglobin, reticulocytes, hematocrit, MCV, leukocyte count (total and differential), and platelets

Time: 0, 2,4,6,8 weeks, 3,4,5,6,7,8,9,10,11,12 months, 5 weeks posttreatment

Measure: Urine trace metals

Time: 0, 6 and 12 months

Measure: Bone marrow sample

Time: 0, 6 and 12 months

Other Outcomes

Measure: Pregnancy urin test (hCG)

Time: 0, 6 and 12 months, 5 weeks posttreatment

35 Sitagliptin Versus Placebo in the Treatment of Non-alcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), the progressive form of liver disease that can lead to cirrhosis and liver-related mortality in persons who drink little or no alcohol. NAFLD is defined as the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes. NASH is defined as the presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis. NASH is benign in many affected individuals but can cause progressive liver injury and, indeed, may be the major cause of cryptogenic cirrhosis1. Currently, there is no FDA approved treatment for NAFLD. Weight loss and exercise are the recommended but often difficult maintain these lifestyle changes in the long term and therefore therapeutic agents have been investigated. In this study, we propose to treat 50 patients with NAFLD and diabetes with either sitagliptin or placebo for 24 weeks. After an initial evaluation for insulin sensitivity and MRI liver fat distribution, patients will receive either 100 mg/day of sitagliptin or placebo. Patients will be monitored at regular intervals for symptoms of liver disease, side effects of sitagliptin and serum biochemical and metabolic indices. At the end of 24-weeks, patients will have a repeat medical evaluation, liver MRI and an optional liver biopsy. Pre and post treatment MRI-derived liver fat content and insulin sensitivity will be compared. The primary end point of successful therapy will be improvement in hepatic steatosis measured by MRI. Secondary end points will be improvement in insulin sensitivity and liver biochemistry.

NCT01963845 Non-alcoholic Fatty Liver Disease Drug: Sitagliptin Drug: Placebo
MeSH:Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Abnormality of the liver Decreased liver function Elevated hepatic transaminase Hepatic steatosis

- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Primary Outcomes

Description: Participants liver fat was measured at baseline and 24 weeks. This is the percentage change in liver fat assessed by MRI-PDFF and stratified by treatment group.

Measure: Percentage Change in Liver Fat Relative to Baseline Assessed by MRI-PDFF

Time: Baseline and 24 weeks

Secondary Outcomes

Description: AST, measured in IU/L at baseline and 24 weeks

Measure: AST, Aspartate Aminotransferase

Time: Baseline and 24 weeks

Description: ALT, measured in IU/L at baseline and 24 weeks

Measure: ALT, Alanine Aminotransferase

Time: Baseline and 24 weeks

Description: LDL, measured in mg/dL at baseline and 24 weeks

Measure: LDL, Low-density Lipoprotein

Time: Baseline and 24 weeks

Description: HOMA-IR, calculated as [(glucose (mg/dL) X insulin (mg/dL)) / 405 ] at baseline and 24 weeks

Measure: HOMA-IR, Homeostatic Model Assessment of Insulin Resistance

Time: Baseline and 24 weeks

36 Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study

Treatment of refractory hemochromatosis rheumatism by Anakinra. Prospective, multicenter, non-randomised, single-arm, open-label, phase II trial.

NCT02263638 Refractory Hemochromatosis Rheumatism Drug: Anakinra
MeSH:Rheumatic Diseases Hemochromatosis Collagen Diseases

Inclusion Criteria: - Patients with age equal to or over 18 years old, - Patients with proved hereditary hemochromatosis with homozygosity for the C282Y mutation of the HFE gene, - Patients with rheumatism related to hemochromatosis, considered by the rheumatologist refractory to usual treatment defined by a persistent painful symptomatology despite a treatment of at least one month with level 2 analgesics (weak opioids) at maximal dose, NSAID, colchicine, steroid injection or a combination of these treatments, - Patients with pain > 40/100mm measured by VAS (pain of the last 48 hours), - Effective contraception to be used during treatment and until 48h after the last administration for women of reproductive age, - Patients who have given written informed consent. --- C282Y ---

Primary Outcomes

Description: Improvement is defined as the minimal clinically important improvement of joint pain and is assessed on a 0-100 mm visual analogue scale (VAS)

Measure: Rate of patients with improvement of joint pain

Time: Day 15

Secondary Outcomes

Description: Assessment of the disease activity by Visual analog scale (VAS)

Measure: Assessment of the disease activity

Time: Day 0, day 15, day 30, day 60, day 90

Description: Assessment of the number of painful joints by a clinical exam

Measure: Assessment of the number of painful joints

Time: Day 0, day 15, day 30, day 60, day 90

Description: Assessment of the number of swollen joints by a clinical exam

Measure: Assessment of the number of swollen joints

Time: Day 0, day 15, day 30, day 60, day 90

Measure: Assessment of analgesics consumption

Time: Day 0, day 15, day 30, day 60, day 90

Measure: Assessment of non-steroidal anti-inflammatory drugs (NSAID) consumption

Time: Day 0, day 15, day 30, day 60, day 90

Measure: Assessment of colchicine consumption

Time: Day 0, day 15, day 30, day 60, day 90

Measure: Assessment of steroids injections consumption

Time: Day 0, day 15, day 30, day 60, day 90

Description: Assessment of the quality of life by the SF36 questionnaire

Measure: Assessment of the quality of life

Time: Day 0, day 15, day 30, day 90

Description: Assessment of the quality of life by the HAQ questionnaire

Measure: Assessment of the quality of life

Time: Day 0, day 15, day 30, day 90

Description: Functional evaluation by WOMAC index for hip and knee

Measure: Functional evaluation

Time: Day 0, day 15, day 30, day 90

Description: Functional evaluation by Dreiser index for hands

Measure: Functional evaluation

Time: Day 0, day 15, day 30, day 90

Description: Assessment of joint damage by X-rays and Doppler ultrasound

Measure: Assessment of joint damage

Time: Day 0, day 90

Description: Puncture if acute joint effusion : cells count

Measure: Synovial fluid analysis

Time: 3 months

Description: Puncture if acute joint effusion : search for crystals presence

Measure: Synovial fluid analysis

Time: 3 months

Description: Puncture if acute joint effusion : iron parameters markers

Measure: Synovial fluid analysis

Time: 3 months

Description: Biological/Vaccine : iron and inflammatory markers

Measure: Biological effects on inflammation and iron metabolism

Time: Day 0, day 15, day 30, day 60, day 90

Description: Pharmacokinetics study

Measure: Time at which Cmax of anakinra was observed (Tmax)

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

Description: Pharmacokinetics study

Measure: Maximum observed concentration (Cmax) of anakinra

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

Description: Pharmacokinetics study

Measure: Half-life (T1/2) of anakinra

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

Description: Pharmacokinetics study

Measure: Area under the concentration-time curve of time 0 to the last detectable concentration (AUC0−last) of anakinra

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

Description: Pharmacokinetics study

Measure: Area under the concentration-time curve of time 0 to infinity (AUC0−∞) of anakinra

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

Description: Pharmacokinetics study

Measure: Plasma clearance after administration (CL/F) of anakinra

Time: Predose, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21, 24 hours post-dose

37 Natural History of Noncirrhotic Portal Hypertension

Background: - Noncirrhotic Portal Hypertension (NCPH) is caused by liver diseases that increase pressure in the blood vessels of the liver. It seems to start slowly and not have many warning signs. Many people may not even know that they have a liver disease. There are no specific treatments for NCPH. Objectives: - To learn more about how NCPH develops over time. Eligibility: - People age 12 and older who have NCPH or are at risk for getting it. In the past year, they cannot have had other types of liver disease that typically result in cirrhosis, liver cancer, or active substance abuse. Design: - Participants will have 2 screening visits. - Visit 1: to see if they have or may develop NCPH. - Medical history - Physical exam - Urine and stool studies - Abdominal ultrasound - Fibroscan. Sound waves measure liver stiffness. - Visit 2: - Blood tests - Abdominal MRI - Echocardiogram - Questionnaire - Liver blood vessel pressure (hepatic venous portal gradient (HVPG)) measurement. This is done with a small tube inserted in a neck vein. - They may have a liver biopsy. - All participants will visit the clinic every 6 months for a history, physical exam, and blood tests. They will also repeat some of the screening tests yearly. - Participants with NCPH will also have: - Upper endoscopy test. A tube inserted in the mouth goes through the esophagus and stomach. - At least every 2 years: Esophagogastroduodenoscopy. - At least every 4 years: testing including HVPG measurements and liver biopsy. - Participants without NCPH will also have: - Liver biopsy and HVPG measurements to see if they have NCPH. - Every 2 years: abdominal MRI and stool studies. - The study will last indefinitely.

NCT02417740 Cystic Fibrosis Immunologic Deficiency Syndrome Turner Syndrome Congenital Hepatic Fibrosis Idiopathic Non-Cirrhotic Portal Hypertension
MeSH:Cystic Fibrosis Hypertension, Portal Turner Syndrome Hypertension Immunologic Deficiency Syndromes Syndrome Fibrosis
HPO:Hypertension Immunodeficiency Portal hypertension

- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy or homozygosity for C282Y. --- C282Y ---

Primary Outcomes

Description: natural history study

Measure: To study the natural history of non cirrhotic portal hypertension. It is an ongoing study

Time: Ongoing

38 Hepcicor Cohort : Clinical, Biological, Genetic and Fonctional charactérization of Rare Iron Overlaod phénotypes Associated With Hepcidin Deficiency Excluding C282Y Homozygosity

The study explores the hepcidin deficiency causes of rare iron overload (excluding C282Y homozygosity), and aim to characterize this iron overload in term of clinical, biological, genetic and functional spacificities.

NCT02619955 Rare Iron Overlaods Other: samples with DNA

Hepcicor Cohort : Clinical, Biological, Genetic and Fonctional charactérization of Rare Iron Overlaod phénotypes Associated With Hepcidin Deficiency Excluding C282Y Homozygosity. --- C282Y ---

Cohort of Patients With Rare Iron Overloads Excluding C282Y Homozygosity The study explores the hepcidin deficiency causes of rare iron overload (excluding C282Y homozygosity), and aim to characterize this iron overload in term of clinical, biological, genetic and functional spacificities. --- C282Y ---

Cohort of Patients With Rare Iron Overloads Excluding C282Y Homozygosity The study explores the hepcidin deficiency causes of rare iron overload (excluding C282Y homozygosity), and aim to characterize this iron overload in term of clinical, biological, genetic and functional spacificities. --- C282Y --- --- C282Y ---

to characterize these iron overloads with phenotype of hepcidin deficiency not related to homozygosity C282Y (clinical, biological and genetic).. comparison of the hepcidin and hepcidin/ferritin ratio in patient with or without in gene known to be associated with iron metabolism. --- C282Y ---

Exclusion Criteria: - HFE hemochromatosis: homozygosity C282Y/C282Y - Treatment with iterative phlebotomy - Hematologic diseases with dyserythropoiesis and/or repeated transfusions - Haptoglobin low, below normal directing towards the diagnosis of chronic hemolysis, myelodysplasia - Prolonged oral or parenteral iron supplementation - Current or past excessive regular drinking - Patient minor or under legal protection measure Inclusion Criteria: - Biological profile suggestive of hepcidin deficiency: - increase of transferrin saturation coefficient (> 50 %) verified on at least 2 times, and calculated from the transferrinemia. --- C282Y ---

Exclusion Criteria: - HFE hemochromatosis: homozygosity C282Y/C282Y - Treatment with iterative phlebotomy - Hematologic diseases with dyserythropoiesis and/or repeated transfusions - Haptoglobin low, below normal directing towards the diagnosis of chronic hemolysis, myelodysplasia - Prolonged oral or parenteral iron supplementation - Current or past excessive regular drinking - Patient minor or under legal protection measure Rare Iron Overlaods Chronic iron overload are responsible for morbidity and mortality. --- C282Y ---

The main objective of this study is to characterize these iron overloads with phenotype of hepcidin deficiency not related to homozygosity C282Y (clinical, biological and genetic). --- C282Y ---

Primary Outcomes

Description: to characterize these iron overloads with phenotype of hepcidin deficiency not related to homozygosity C282Y (clinical, biological and genetic).

Measure: Number of patients presenting with mutation in gene know to be associated with iron metabolism

Time: Inclusion

Secondary Outcomes

Description: To Identificate potential explanatory factors of hepcidino deficiency phenotype

Measure: comparison of the hepcidin and hepcidin/ferritin ratio in patient with or without in gene known to be associated with iron metabolism

Time: inclusion

Description: - Identification of potentially explanatory factors visceral consequences of iron overload in hepcidino deficiency phenotype (overweight, high blood pressure, diabetes)

Measure: Number of patients presenting with associated causes of iron overload

Time: inclusion

Description: To Research correlations genotype-phenotype

Measure: Genotype-Phenotype correlation

Time: Inclusion

Description: Validation of the hepatic iron concentration measurements imaging ( nuclear magnetic resonance (NMR)) in the various centers

Measure: Hepatic and splenic iron concentration measurements by NMR

Time: Inclusion

Description: - Assessment of the clinical value of biomarkers of iron metabolism

Measure: Number of patients with detectable abnormal iron species in blood (non transferrin bound iron, labile pool iron)

Time: Inclusion

39 Aramchol Versus Placebo in the Treatment of HIV-associated Nonalcoholic Fatty Liver Disease and Lipodystrophy: A Randomized, Double-blinded, Allocation-concealed, Placebo-controlled Clinical Trial

A subset of patients with NAFLD that have not been extensively studied are those infected with human immunodeficiency virus (HIV). Currently, there is no FDA approved treatment for NAFLD or NASH. Additionally, there have been no significant clinical trials for HIV patients with NAFLD and there are no approved treatment options. We plan to conduct a randomized, double-blinded, placebo-controlled clinical trial to examine the efficacy of 600 mg of Aramchol daily (including 200 mg tablet and 400 mg tablet) versus identical placebo given over 12 weeks to improve HIV-associated hepatic steatosis as measured by a validated and accurate magnetic resonance imaging (MRI)-based technique.

NCT02684591 Nonalcoholic Fatty Liver Disease HIV Drug: Aramchol Drug: Placebo
MeSH:Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Lipodystrophy
HPO:Abnormality of the liver Decreased liver function Elevated hepatic transaminase Hepatic steatosis Lipodystrophy

Evidence of another form of liver disease: Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg), Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA in serum, Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy, Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with rimary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis, Wilsons disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilsons disease Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D, Drug-induced liver disease as defined on the basis of typical exposure and history,Bile duct obstruction as shown by imaging studies. --- C282Y ---

Primary Outcomes

Description: To examine the efficacy of aramchol at 600 mg orally daily versus placebo in improving hepatic steatosis assessed by magnetic resonance imaging in patients with HIV-associated NAFLD

Measure: Efficacy of Aramchol 600 mg vs. Placebo in Improving Hepatic Steatosis Assessed by Magnetic Resonance Imaging in Patients With HIV-associated NAFLD

Time: 12 weeks

Secondary Outcomes

Description: To examine the efficacy of two doses of aramchol: 200 mg/tablet and 400 mg/tablet / day orally daily versus placebo in improving serum alanine aminotransferase (ALT) levels in patients with HIV-associated NAFLD

Measure: Serum Alanine Aminotransferase (ALT)

Time: 12 Weeks

40 Iron Supplement Effect Over Immune System and Neurobehavioral Child Development.

Objective: To evaluate the effect of Iron supplement with two different amounts (one in the higher limit and another in the lower limit of the suggested amount) according to the presence of mutations in the HFE gene in the physical, immune and neurobehavioral development in the 6 to 12 moth toddlers. Methodology: Subjects: 340 toddlers coming from Paediatric Serves of Sant Joan Hospital. Methods: At 6 and 12 months it done clinical history, food registry, biochemist determinations: haemoglobin, iron, transferrin, ferritin, reactive C protein and immune response (IL4, IL10, IL6 IFN, IgA, IgM, IgG, IgE). Mutations in the HFE gene: C282Y, H63D, S65D and hepcidin gene. Mental, psychomotor and behavioual development (Bayley Scales of Infant Development 2on Edition: 1993). We evaluate the level of language and communication (MacArthur), regulation and sensory process (Infant Toddler Symptom Checklist), familiar and environment surroundings (Scale Health General Parental Stress Index).

NCT02690675 Neurodevelopmental Disorders Lactation Dietary Supplement: Iron fortified formula milk
MeSH:Neurodevelopmental Disorders

Mutations in the HFE gene: C282Y, H63D, S65D and hepcidin gene. --- C282Y ---

Primary Outcomes

Measure: Mental and psychomotor development with BSID (Bayley Scale of Infant Development) at 12 months.

Time: 12 months

Secondary Outcomes

Measure: Height at 12 months measured in centimeters

Time: 12 months

Measure: Weight at 12 months measured in grams

Time: 12 months

Measure: Head circumference at 12 months measured in centimeters

Time: 12 months

Measure: Risk of infections at 12 months measured qualitatively from record of presence or not of various infections as bronchitis, rhinitis, otitis etc.

Time: 12 months

41 A Phase 2,Multicenter,Open-Label Study to Investigate the Efficacy, Safety and Pharmacokinetics of Ritonavir-boosted Danoprevir in Combination With Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients Who Have Chronic Hepatitis GT1

The purpose of this study is to evaluate the Efficacy, Safety and Pharmacokinetics of Ritonavir-boosted Danoprevir (ASC08) in Combination with Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients Who Have Chronic Hepatitis Genotype 1.

NCT03020004 Chronic Hepatitis C Drug: Danoprevir Drug: Ritonavir Drug: peginterferon alfa-2a Drug: Ribavirin (RBV)
MeSH:Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic
HPO:Chronic active hepatitis Chronic hepatitis Hepatitis

Patients who have not obtained a liver biopsy or Fibroscan in the last 1 years will have a study related Fibroscan performed in order to confirm the diagnosis - Others as specified in the detailed protocol Exclusion Criteria: - Patients with Fibroscan detection value > 12.9 kPa, or histologic examination for liver cirrhosis patients - Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy - Patients with a history of liver cell cancer, screening before or screening suspected hepatocellular carcinoma (HCC) patients, or imaging studies found suspicious nodules, or AFP > 50 ng/mL - Positive hepatitis A antibody,positive hepatitis B surface antigen,syphilis antibody or HIV antibody at screening - Others as specified in the detailed protocol Inclusion Criteria: - Willing and able to provide written informed consent - Chronic HCV infection (≥ 6 months) ; - Positive HCV antibody - Serum HCV RNA of ≥ 1 × 104 IU/mL - Hepatitis C virus GT1 - Never received prior-treatment for HCV with interferon, RBV, or other direct-acting or host-targeting antivirals for HCV - The liver biopsy methods in the protocol (non-cirrhosis is defined as: Metavir score ˂ 4), or as determined by Fibroscan defined as: ˂ 14.6 kPa. --- C282Y ---

Patients who have not obtained a liver biopsy or Fibroscan in the last 1 years will have a study related Fibroscan performed in order to confirm the diagnosis - Others as specified in the detailed protocol Exclusion Criteria: - Patients with Fibroscan detection value > 12.9 kPa, or histologic examination for liver cirrhosis patients - Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy - Patients with a history of liver cell cancer, screening before or screening suspected hepatocellular carcinoma (HCC) patients, or imaging studies found suspicious nodules, or AFP > 50 ng/mL - Positive hepatitis A antibody,positive hepatitis B surface antigen,syphilis antibody or HIV antibody at screening - Others as specified in the detailed protocol Chronic Hepatitis C Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic null --- C282Y ---

Primary Outcomes

Description: SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration

Measure: Percentage of Subjects With Sustained Virologic Response (SVR12) 12 Weeks Post-treatment

Time: 24 weeks

42 Phase 2 Study To Investigate the Efficacy, Safety And Pharmacokinetics Of Ravidasvir In Combination With Ritonavir-boosted Danoprevir And Ribavirin In Treatment-naive Non-cirrhotic Taiwanese Patients Who Have Chronic Hepatitis C Genotype 1

The purpose of this study is to evaluate the efficacy, safety and tolerability of Ravidasvir (ASC16) in combination with Ritonavir-boosted Danoprevir(ASC08) and Ribavirin in treatment-naive no-cirrhotic Taiwanese patients who have chronic hepatitis C genotype1.

NCT03020095 Chronic Hepatitis C Drug: Ravidasvir Drug: Danoprevir Drug: Ritonavir Drug: Ribavirin
MeSH:Hepatitis C Hepatitis C, Chronic Hepatitis Hepatitis, Chronic
HPO:Chronic active hepatitis Chronic hepatitis Hepatitis

- History or presence of decompensated liver disease (history of ascites, hepatic encephalopathy, HCC, or bleeding esophageal varices) - Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy - Positive hepatitis B surface antigen or HIV antibody at screening - History or presence of liver cirrhosis - History of severe psychiatric disease, including psychosis and/or depression, who is not able to participate or able to give written informed consent and to comply with the study restrictions - History of active malignancy within the last 5 years, with the exception of localized or in situ carcinoma (e.g., basal or squamous cell carcinoma of the skin) - History of severe cardiac disease (e.g., New York Heart Association Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmia's requiring ongoing treatment, unstable angina or other unstable, uncontrolled or significant cardiovascular disease within 6 months). --- C282Y ---

Primary Outcomes

Description: SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration

Measure: Proportion of participants with Sustained Virologic Response 12 weeks after end of treatment (SVR12)

Time: 12 weeks

Secondary Outcomes

Measure: Proportion of participants permanently discontinuing study drug(s) due to an adverse event (AE)

Time: 24 weeks

Description: SVR24, defined as undetectable HCV RNA 24 weeks after the last day of study drug administration

Measure: Proportion of participants with Sustained virologic response 24 weeks after end of treatment

Time: 24 weeks

43 Effectiveness of Adaptation of the Dose of Iron Supplementation in Pregnancy on Maternal-child Health. Randomized Clinical Trial (ECLIPSES)

Currently, there is no consensus regarding iron supplementation dose that is most beneficial for maternal and offspring health during gestation. This deficit, or excess, of iron prejudices the mother-child wellbeing. Therefore the hypotheses are that an iron supplementation adapted to values of hemoglobin at the start of the pregnancy will would be more effective in preventing iron deficiency, without increasing the risk of hemoconcentration by the end of pregnancy. This would be helped optimize mother-child health status. The aims of the study are to determine the highest level of effectiveness of iron supplementation adapted to hemoglobin (Hb) levels in early pregnancy, which would be optimum for mother-child health. To accomplish this objective a Randomized Clinical Trial (RCT) triple-blinded was designed. The study is structured as a RCT with 2 strata, depending on the Hb levels before week 12 of gestation. Stratum 1: If Hb from 110 to 130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 80 mg/d. Stratum 2: If Hb >130 g/L, randomly assigned at week 12 to receive iron supplement of 40 or 20 mg/d. This study will be conducted in non-anemic pregnant women at early gestation stage, and their subsequent newborns. The data recollected to mothers will be: socio-economic data, clinical history, food item frequency, lifestyle and emotional state, and adherence to iron supplement prescription. In addition, biochemical measured will be Hemoglobin, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). In children, the data collected will be: ultrasound fetal biometry, anthropometric measurements, and temperament development Should conclusive outcomes be reached, the study would indicate the optimal iron supplementation dose required to promote maternal and infant health. These results would contribute towards developing guidelines for good clinical practice.

NCT03196882 Anemia Ferropenic Risk of Hemoconcentration (Iron Levels Risk of Hemoconcentration (Iron Levels > Risk of Hemoconcentration (Iron Levels >130g/L) Drug: 40mg/day of iron Drug: 20mg/day of iron Drug: 80mg/day of iron
MeSH:Anemia Anemia, Iron-Deficiency
HPO:Anemia Iron deficiency anemia

In addition, biochemical measured will be Hemoglobin, serum ferritin, C reactive protein, cortisol, and alterations in the HFE gene (C282Y, H63D). --- C282Y ---

- Hemoconcentration risk is defined as: Hb >130 g/L in the 2nd and /or3rd trimester (Peña-Rosas y Viteri, 2009).. C282Y polymorphisms of HFE gene. --- C282Y ---

Presence or absence of polymorphisms: C282Y and H63D. --- C282Y ---

Primary Outcomes

Description: - Anemia is defined as Hb <110 g/L in the 1st and 3rd trimester, Hb <110 in 2nd trimester (Centers for Disease Control and Prevention, 1998).

Measure: Anemia

Time: at week 36 of gestation (3rd visit of study)

Description: - Ferropenic anemia is defined as: Hb < the normal limit, and serum ferritin (SF) <15 μg/L (WHO, 2007)

Measure: ferropenic anemia

Time: at week 36 of gestation (3rd visit of study)

Description: - Hemoconcentration risk is defined as: Hb >130 g/L in the 2nd and /or3rd trimester (Peña-Rosas y Viteri, 2009).

Measure: Risk of hemoconcentration

Time: at week 36 of gestation (3rd visit of study)

Secondary Outcomes

Description: Presence or absence of polymorphisms: C282Y and H63D

Measure: C282Y polymorphisms of HFE gene

Time: Blood analysis at 12 weeks of gestation.

Description: weight (g)

Measure: Anthropometric parameters of newborn.

Time: At birth

Description: Units on a scale (score).

Measure: Neurorconductual development of newborn (Bayley Scales)

Time: 40days post-partum

Description: Presence or absence of polymorphisms: C282Y and H63D

Measure: H63D polymorphisms of HFE gene

Time: Blood analysis at 12 weeks of gestation.

44 A Phase II, Multicenter, Open-label, Randomized Two-year Study to Evaluate the Efficacy and Safety of Deferasirox Film-coated Tablet Versus Phlebotomy in Patients With Hereditary Hemochromatosis.

The purpose of this study is to evaluate the efficacy and safety of deferasirox film coated tablet (FCT) versus phlebotomy for the management of iron overload in adults with HH at risk of iron-related morbidity. This evaluation will provide information on the two treatment options in terms of the rate of response of proportion of patients reaching the study target SF ≤ 100 μg/L and their associated safety profiles. In addition to exploring the safety and efficacy of deferasirox FCT in hereditary hemochromatosis (HH), this study is being conducted to fulfill an FDA post-marketing requirement [PMC 750-10 (Exjade) /PMR 2888-8 (Jadenu)] to provide additional randomized data to confirm the ocular safety profile of deferasirox through detailed ocular assessments in patients treated with deferasirox FCT for 2 years.

NCT03203850 Hereditary Hemochromatosis Drug: Deferasirox FCT Procedure: Phlebotomy
MeSH:Hemochromatosis

Male or female ≥ 18-years-old 2. Documented genotype testing confirming homozygous for the C282Y mutation (C282Y/C282Y) 3. Transferrin saturation ≥ 45% (at either screening visit) 4. Serum ferritin (SF) ≥ 500 μg/L (at either screening visit) - Exclusion Criteria: 1. Medical conditions that preclude inclusion: - Iron overload not due to HH - Condition which might significantly alter the absorption, distribution, metabolism or excretion of oral deferasirox - Systemic disease which prevents taking study treatment or any contraindication to phlebotomy - Inflammatory condition or immunological disease which may interfere with the SF interpretation, such as an active infection, collagen vascular disorders, irritable bowel syndrome, lupus, or immune thrombocytopenia - Significantly impaired gastrointestinal function or disease that may significantly alter the absorption of oral deferasirox, e.g. --- C282Y ---

Male or female ≥ 18-years-old 2. Documented genotype testing confirming homozygous for the C282Y mutation (C282Y/C282Y) 3. Transferrin saturation ≥ 45% (at either screening visit) 4. Serum ferritin (SF) ≥ 500 μg/L (at either screening visit) - Exclusion Criteria: 1. Medical conditions that preclude inclusion: - Iron overload not due to HH - Condition which might significantly alter the absorption, distribution, metabolism or excretion of oral deferasirox - Systemic disease which prevents taking study treatment or any contraindication to phlebotomy - Inflammatory condition or immunological disease which may interfere with the SF interpretation, such as an active infection, collagen vascular disorders, irritable bowel syndrome, lupus, or immune thrombocytopenia - Significantly impaired gastrointestinal function or disease that may significantly alter the absorption of oral deferasirox, e.g. --- C282Y --- --- C282Y ---

Primary Outcomes

Description: Assess the response rate (RR) of deferasirox film coated tablet (FCT) and phlebotomy treatment arms where response is defined by achieving target serum ferritin (SF) ≤ 100 μg/L on or before 24 months. Estimate of the RR and corresponding 95% confidence interval (CI) will be provided for each arm. No formal hypothesis testing is planned in this study.

Measure: Proportion of patients achieving target SF ≤ 100 μg/L for the first time.

Time: Response is defined by achieving target SF ≤ 100 μg/L on or before 24 months.

Secondary Outcomes

Description: To evaluate the ocular safety of deferasirox FCT and phlebotomy over 24 months. To characterize long-term ocular safety by the incidence of treatment-emergent ocular adverse events (AEs) (new or worsening from baseline) summarized categorically by system organ class and/or preferred term.

Measure: Incidence of ocular adverse events (AEs) overall

Time: 24 months

Description: To evaluate the ocular safety of deferasirox FCT and phlebotomy over 24 months. To characterize long-term ocular safety by AE severity (new or worsening from baseline) summarized categorically by system organ class and/or preferred term.

Measure: Incidence of ocular adverse events (AEs) by severity

Time: 24 months

45 Prospective Cohort Assessing the Prevalence and Progress of Non-alcoholic Fatty Liver Disease (NAFLD)/Non-alcoholic Steatohepatitis (NASH) in Chinese

Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease ranging from simple steatosis to cirrhosis of the liver. Nonalcoholic fatty liver (NAFL) without substantial hepatocellular injury is thought to be relatively benign whereas nonalcoholic steatohepatitis (NASH) is characterized by hepatocyte steatosis, ballooning, inflammation and varying degrees of fibrosis from none to cirrhosis. NASH is strongly associated with insulin resistance and metabolic syndrome and thus is recognized as a major public health concern as the most prevalent liver disease. Liver biopsy is the gold standard for a diagnosis of NASH. However, given the large population of patients at risk for NASH, liver biopsy is not a practical method for determining which patients may benefit from NASH therapy. Non-invasive methods to estimate inflammation and fibrosis are in clinical use, but there remains a dichotomy between gold standard inclusion criteria and end points that are utilized in clinical trials and real world diagnostic methods that are more common in clinical practice. Thus, the investigators would like to conduct an observational study to head-to-head compare the non-invasive methods and liver biopsy in differential liver steatosis and liver biopsy in a real-world setting. Also, by following up patients for a relatively long time (proposed 10 years), the investigators can present the natural history of disease progression.

NCT03282305 Nonalcoholic Fatty Liver Nonalcoholic Steatohepatitis
MeSH:Fatty Liv Fatty Liver Non-alcoholic Fatty Liver Disease
HPO:Hepatic steatosis

Exclusion Criteria: - Unable to provide written informed consent (or assent in pediatric subjects) - Alcohol consumption greater than 21 units/week for males or 14 units/week for females (one unit of alcohol is half pint of beer [285 mL; 9.64 oz], 1 glass of spirits [25 mL; 0.85 oz] or 1 glass of wine [125 mL; 4.23 oz] - Enrolled in NASH-related clinical trials - Presence of other forms of chronic liver disease: 1. Chronic hepatitis B (HBsAg positive) 2. Chronic hepatitis C (HCV RNA positive) 3. Iron overload disorders (3-4+ iron on liver biopsy or known hemochromatosis gene (HFE) C282Y homozygous with ferritin > 200 ng/ml; note: an elevated ferritin alone is common in NASH and is not exclusionary) 4. Autoimmune liver disease (biopsy evidence or clinical diagnosis of autoimmune hepatitis or Primary biliary cholangitis (PBC) requiring ongoing treatment, imaging evidence of Primary sclerosing cholangitis (PSC)) 5. Wilson's disease 6. Alpha-1 antitrypsin mutations that in the opinion of the principal investigator is contributing to the patient's liver disease; - Prior bariatric surgery unless the surgery was performed more than one year before the biopsy diagnosis of NASH (i.e., NASH is present despite prior bariatric surgery); - Planned bariatric surgery (e.g. --- C282Y ---

Primary Outcomes

Description: The change in NASH Clinical Research Network (CRN) score based on liver biopsy

Measure: Histological endpoint

Time: 10 years

Secondary Outcomes

Description: Number of all-cause death

Measure: Number of all-cause death

Time: 10 years

Description: Number of liver-related death

Measure: Number of liver-related death

Time: 10 years

Description: Number of liver transplant

Measure: Number of liver transplant

Time: 10 years

Description: Number of hepatocellular carcinoma (HCC)

Measure: Number of hepatocellular carcinoma (HCC)

Time: 10 years

46 Study of the Association Between Transferrin Saturation and Asthenia in Hemochromatosis

Observational study.

NCT03356548 Hemochromatoses, Genetic
MeSH:Hemochromatosis Asthenia

- Inclusion criteria: - homozygous C282Y ; - in the maintenance phase for at least 6 months ; - follow-up at Rennes University Hospital ; - patient who has not expressed his opposition to participate in the study. --- C282Y ---

Hemochromatoses, Genetic Hemochromatosis Asthenia The linked HFE genetic hemochromatosis (C282Y mutation in the homozygous state) is the most common form of genetic iron overload. --- C282Y ---

Our objective is to evaluate, in patients homozygous C282Y in maintenance phase, the association between quality of life and Transferrin Saturation Coefficient . --- C282Y ---

Primary Outcomes

Measure: Quality of life questionnaire SF 36

Time: Through study completion, an average of 3 months

Measure: Biological markers : Transferrin Saturation Coefficient

Time: Through study completion, an average of 3 months

47 Effects of Polyphenols on Iron Absorption in Iron Overload Disorders.

Dysmetabolic iron overload syndrome and genetic hemochromatosis are frequent causes of iron overload. Polyphenols are efficient iron-chelators. Investigator hypothesize that polyphenol supplementation can reduce iron absorption in iron overload disease. Iron absorption can be studied by the area-under-the-curve of serum iron after iron oral loading. The primary outcome is the decrease of post-prandial serum iron after rich-iron meal, due to polyphenol supplementation.

NCT03453918 Dysmetabolic Iron Overload Syndrome Geneti Genetic Hemochromatosis Iron Absorption Polyphenols Dietary Supplement: polyphenols Other: Placebo
MeSH:Hemochromatosis Iron Overload Syndrome

- For Genetic Haemochromatosis type 1 Group: homozygosity mutation C282Y in HFE gene ; patients undergoing therapeutic phlebotomies. --- C282Y ---

Primary Outcomes

Description: decrease of intestinal iron absorption after standardized oral loading dose through rich-iron meal, expressed by area-under-the-curve of serum iron, due to concomitant administration of a single dose of dietary polyphenos (nutrient complement) versus placebo administration. This outcome is a quantitative variable, treated and analysed as such.

Measure: Decrease of post-prandial iron absorption after dietary polyphenol supplementation

Time: at day 3

Secondary Outcomes

Description: comparison of oxylipin levels, through lipidomic analyses by spectrophotometry

Measure: Post-prandial changes of circulating oxylipin in iron overload diseases after iron-rich meal and effects of polyphenols supplementation

Time: at day 1 (fasting versus 3 hours after rich-iron meal, versus 3 hours after rich-iron meal with polyphenol supplementation)

Description: comparison of oxylipin levels, through lipidomic analyses by spectrophotometry. Healthy subjects datas comes from a previous study (MEPHISTO).

Measure: Comparison of oxylipin levels between DIOS, genetic hemochromatosis and healthy subjects after 6 hours of fasting.

Time: at baseline

48 Testing the Efficacy of a Natural Polyphenol Supplement to Inhibit Dietary Iron Absorption in Subjects With Hereditary Hemochromatosis: a Stable Isotope Study

Polyphenolic compounds are very strong Inhibitors of non-heme iron absorption, as they form insoluble complexes with ferrous iron. Patients with hereditary hemochromatosis (HH) have an increased intestinal non-heme iron absorption due to a genetic mutation in the regulatory pathway, leading to excess iron in the body. This study investigates the inhibitory effect of a natural polyphenol Supplement in participants with HH.

NCT03990181 Iron Metabolism Disorders Iron Overload Polyphenols Dietary Supplement: meal matrix & NPPS Dietary Supplement: meal matrix & CS Dietary Supplement: no-matrix & NPPS Dietary Supplement: no-matrix & CS
MeSH:Hemochromatosis Iron Overload Metabolic Diseases Iron Metabolism Disorders

Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Iron Metabolism Disorders Iron Overload Polyphenols Hemochromatosis Iron Overload Metabolic Diseases Iron Metabolism Disorders null --- C282Y ---

Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Inclusion Criteria: - Homozygous for C282Y mutation in HFE (hemochromatosis) gene - Written informed consent - Age 18-65 y - Not pregnant or lactating - Body weight < 75 kg - Body mass index (BMI) between 18.5 and 25 kg/m2 - No acute illness/infection (self-reported) - No metabolic or gastrointestinal disorders, eating disorders or food allergy to the ingredients of the test meal (self-reported) - No scheduled phlebotomy throughout the study period - The last phlebotomy will be at least 4 weeks prior first test meal administration - No use of medications affecting iron absorption or metabolism during the study - No intake of mineral/vitamin supplements 2 weeks before the first study day and during the study - Participation in any other clinical study within the last 30 days - Expected to comply with study protocol Iron Metabolism Disorders Iron Overload Polyphenols Hemochromatosis Iron Overload Metabolic Diseases Iron Metabolism Disorders null --- C282Y --- --- C282Y ---

Primary Outcomes

Description: The change in the isotopic ratio of iron will be measured after administration of a test meal/drink including iron isotopes

Measure: change from baseline in the isotopic ratio of iron in blood at week 2

Time: baseline, 2 weeks

Description: The change in the isotopic ratio of iron will be measured after administration of a test meal/drink including iron isotopes

Measure: change from baseline in the isotopic ratio of iron in blood at week 4

Time: 2 weeks, 4 weeks

Secondary Outcomes

Description: to assess iron status

Measure: Serum Ferritin concentration (µg/L)

Time: baseline, weeks 2, and 4

Description: to assess iron status

Measure: Serum iron concentration (µg/dL)

Time: baseline, weeks 2, and 4

Description: to assess iron status

Measure: Soluble transferrin receptor (mg/L)

Time: baseline, weeks 2, and 4

Description: to calculate percent of transferrin that has iron bound to it; Plasma iron and transferrin saturation will be combined to calculate transferrin saturation (ratio)

Measure: Transferrin saturation in %

Time: baseline, weeks 2, and 4

Description: to assess blood volume based on weight, height, and Hb.

Measure: Hemoglobin (g/dL)

Time: baseline, weeks 2, and 4

Description: identify acute inflammation

Measure: C-reactive Protein (mg/L)

Time: baseline, weeks 2, and 4

Description: identify chronic inflammation

Measure: alpha-1-glycoprotein (g/L)

Time: baseline, weeks 2, and 4

Description: the major regulator of non-heme iron absorption

Measure: Serum Hepcidin (nM)

Time: baseline, and weeks 2

49 Haemochromatosis and Periodontitis

Periodontitis is a chronic inflammatory disease that affects tissues surrounding the teeth. It is strongly associated with the major pathogenic "red complex", including Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola1 and thus is considered an infection. Recent advances in the pathogenesis of periodontal disease have suggested that polymicrobial synergy and microbiota dysbiosis together with a dysregulated immune response can induce inflammation-mediated damage in periodontal tissues2-4. Interestingly, currently periodontitis is associated with a growing number of systemic diseases, including cardiovascular diseases, adverse pregnancy outcomes, diabetes5-7 and hereditary haemochromatosis8.

NCT04006249 to Evaluate the Prevalence of Periodontal Diseases in Patients With Hemochromatosis at the Time of Diagnosis and / or Their Usual Therapeutic Diagnostic Test: dental probes
MeSH:Periodontitis Periodontal Diseases Hemochromatosis
HPO:Periodontitis

Inclusion Criteria: - Patients aged 35 to 64 years with homozygosity hemochromatosis C282Y - Patients regularly enrolled in a health insurance plan - Patients with at least 10 natural teeth - Patients who have given informed written, dated and signed consent Exclusion Criteria: - Diabetic patients - Simultaneous participation in another study - Pregnant or lactating women - The incapacitated persons and persons deprived of their liberty - Patients who do not speak French, both written and spoken - Patients previously included in this trial - Patients with heart valves or endovascular equipment (risk of infective endocarditis ...) - Patients with a history of maxillofacial surgery - Patients whose oral status is considered incompatible with entry into the study, at the discretion of the investigator - Patients on drugs that can cause gingival hypertrophy, such as Hydantoins (phenytoin), Dihydropyridines, Diltiazem or Ciclosporin - Patients on medication that can cause gingival bleeding (anticoagulants, antiplatelet agents and aspirin). --- C282Y ---

Primary Outcomes

Description: To evaluate the prevalence of periodontal diseases in patients with hemochromatosis at the time of diagnosis and / or their usual therapeutic

Measure: prevalence of periodontal diseases

Time: 2 years

50 Non Alcoholic Fatty Liver Disease and Coronary Heart Disease in Type 2 Diabetes Patients

To assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis, by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) to estimate hepatic stiffness.

NCT04462081 Nonalcoholic Steatohepatitis
MeSH:Liver Diseases Fatty Liver Non-alcoholic Fatty Liver Disease Heart Diseases Coronary Disease Coronary Artery Disease Myocardial Ischemia
HPO:Abnormality of the liver Coronary artery atherosclerosis Decreased liver function Elevated hepatic transaminase Hepatic steatosis Myocardial infarction

- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. --- C282Y ---

Primary Outcomes

Description: Evaluation of liver fat fraction and liver stiffness, as determined by magnetic resonance imaging, are associated with subclinical cardiovascular disease, as evaluated by coronary artery calcium scan in diabetics

Measure: Percentage of Liver Fat as Measured by MRI-PDFF

Time: Baseline


HPO Nodes


HP:0001392: Abnormality of the liver
Genes 1412
PLIN1 CTBP1 CASR BCS1L GLB1 GDF2 SDCCAG8 TCIRG1 MICOS13 RAG1 INSR IFT172 TSC2 CDIN1 IL17F BLNK KCNAB2 FAN1 PHKA2 ARHGAP31 SGSH TSFM STK11 KCNN4 RNASEH2C EPCAM GPC3 RRAS2 OSTM1 CASP10 CC2D2A PDGFRA BRIP1 MOGS SFTPC ASAH1 NDUFAF1 BOLA3 GPR35 LIPE MED25 RAG2 TYMP TTC37 KCNH1 LTBP3 MTRR RNASEH2A PEX1 WDR35 CC2D2A PIEZO1 RHAG TTC7A GPC3 MLH3 FAH NDUFS3 MSH2 AUH IL6 POLG2 ATP7A ALDH7A1 SRD5A3 TRIM32 AXIN1 TCF4 AP1B1 ALG8 RUNX1 SERPINA1 SLC7A7 INS GBA ICOS SETBP1 CFI ALAS2 MYBPC3 SLC35A2 SLC37A4 MRPS16 RPGRIP1 DLD BSCL2 IFT43 PKLR GBA KCNH1 TRNW MRAS PEX12 CIDEC SLX4 PCCA PALB2 PEX10 DHFR OCLN PFKM CASK GLB1 ACADVL COX8A BBS4 TREX1 STX11 AGA POU6F2 ABCG8 TBX19 DAXX HGSNAT CEP290 LIPA MARS1 LRP5 BCS1L SLC25A20 FCGR2A PSMB8 FANCA ARSA CLCN7 MST1 PEX12 TRAPPC11 NCF4 NDUFS6 ARSB CFTR LYST RAG1 TPP2 NBAS FOXF1 UROD F5 ARSA AP1S1 XRCC2 TMEM67 ITCH WDR19 OFD1 UGT1A1 B2M WT1 PDGFRB HYMAI TRAPPC11 UNC13D SRD5A3 SRP54 AGPAT2 TNNI3 TINF2 RHAG HSD17B4 DCLRE1C HSD3B7 NPHP1 ACAT1 ABCA1 PMM2 GTF2IRD1 ND5 IFT80 COG8 UFD1 LETM1 SLC26A4 NDUFS8 NDUFAF3 FANCB SP110 TMEM126B HNRNPA2B1 NPC1 GPIHBP1 DPM3 TSHR RFXANK ICOS LPIN2 FANCM CD3D GPC1 SNX10 LDLR JAK2 ERCC6 POU1F1 COX6B1 TMEM199 PCCA CPT1A LHX4 GPC4 HNF1A HBB GANAB PKHD1 XRCC4 KRT8 TET2 COX14 ATP7B HFE SUMF1 OFD1 DGUOK CD3E ALG13 EXTL3 NCF1 PIK3CA CLIP2 COG6 COMT DCDC2 WDPCP SLC4A1 HLA-DRB1 DPM3 SLC5A5 RMRP GLIS3 PEX26 KCNN4 PLEKHM1 DCDC2 DIS3L2 PEX12 LBR RAB27A TRMT5 NDUFS2 PKLR SMAD4 CALR NDUFV1 APC CFH PEX5 TFAM NEU1 NOTCH1 DMPK DUOX2 HIRA DKC1 BRCA1 ADAR UQCRC2 STEAP3 PCK1 PEX19 IFIH1 DOLK CPLX1 MRPL3 MSH6 PMS1 CTSA APC PKD1 STK11 DYNC2I2 PRSS1 ACADM HBB IGLL1 SOS1 LCAT COG6 STX1A HMGCS2 RNF43 TERT G6PD NSD2 CYTB FBP1 C8ORF37 MKS1 BRCA2 IL2RB PEX2 SLC22A5 TP53 HMGCL MAD2L2 PAX4 IQCB1 WDR19 TMEM67 C11ORF95 FOXP3 IL12RB1 ABCG8 BCS1L TRNL1 PRKCD SLC4A1 TALDO1 HNF1A RAF1 MSH6 TANGO2 ADAMTS13 DYNC2H1 ABCA1 BTK RFXANK ND3 PEX13 C1S NEK1 HK1 TERC NDUFB3 ND6 HBB RPS20 CDKN1C AGA TERC H19 FGA RIT1 PYGL NCF1 CR2 IL2RA MYC ACAD9 MKS1 SLC7A7 CAVIN1 KCNQ1 NFKB2 CLDN1 PEPD MMUT GCK ALG8 PRKCD CTC1 IFT122 PMM2 KRT6A NSMCE2 CDKN2B PALB2 EPB42 NDUFS7 PEX16 SCNN1B HAVCR2 HBA2 ASAH1 RNU4ATAC DHCR7 KMT2E KIT TREX1 SPTB AMACR IL17RC PSAP NAB2 SC5D APC IFT172 DMD EIF2AK3 RECQL4 NGLY1 PEX16 NPHP3 PMS2 PIGM A2ML1 POLG TACO1 LYRM4 SETBP1 CASR ALMS1 ATRX TBX19 GUSB CCDC28B ND3 SLCO2A1 EPB41 CPT2 APOE RNU4ATAC SDHD VHL GCDH B3GLCT CDKN1B PRDM16 BBS5 C4B NEUROG3 ARSA SEC63 HYOU1 NHP2 TNFRSF11A SDHC PRKCSH UROS ATPAF2 PEX13 MSH2 PSAP HESX1 COG4 ALDOB RREB1 DDRGK1 CD40LG IFT140 PEX11B ND1 HNF1B SLC39A8 NPHP3 LMNA CFTR COX10 C1QBP AKR1D1 SMPD1 RFT1 LHX3 PEX3 PC NAGA TMEM216 MMUT BTNL2 ABCG8 TRIM37 SLC25A1 POMC MEN1 USP18 PSAP PEX19 FBN1 NDUFS1 PEX1 TNFRSF13C PDGFB ALG9 LIG4 MKS1 GALNS GBA NAGLU COA8 LMNA MAN2B1 CTSC HMGCL KCNJ11 ANK1 TARS2 TGFBR2 DYNC2I1 KRAS TINF2 FLT1 SLC30A10 SP110 GPD1 SMPD1 ACADL NHLRC2 TRMU HADHA HNF4A FAS PKD1 FANCD2 TPI1 TMEM165 PTPRC TCIRG1 ZIC3 COX10 POLG ADA ABCB4 DMPK PEX2 SEMA4A COG2 POLG2 BAZ1B EXTL3 CYP7B1 ABCD3 UQCRB PCSK9 KRT8 NDUFS4 CTLA4 ASXL1 WT1 LRP5 WDPCP DYNC2LI1 ATP7A EARS2 ASS1 GYPC GCGR GBA MPL CDKN1A DUOXA2 TRIM28 GP1BB CTNNB1 CYP7B1 TGFB1 COA8 HPD CLPB PIK3CA EFL1 BBS12 SBDS CAVIN1 MVK ICOS PAX8 PYGL RAD51 GALT NPHP4 SFTPA2 JAG1 MMUT KIT PEX11B BSCL2 SLCO1B3 FAH PSMB9 SLC17A5 IDUA TRNS1 NFKB1 IFT27 GBA TPO INPP5E STAT1 SDCCAG8 BMPR1A TET2 RAG2 HLA-DRB1 HADHB APC XIAP POLG GNPTAB ESCO2 MS4A1 TTC21B SLC30A10 NAGA ATM NDUFA6 MIF AIRE SEC23B BBS7 UQCRFS1 MPV17 NPHP3 MEFV STXBP2 CBS AKT2 RFX5 CEP164 HMOX1 FH APC GBA RAD51C ACSF3 DIS3L2 KRAS NDUFS4 BTNL2 DNAJC19 LMNA SH2D1A HBA2 ABCB11 ALG1 NDUFA1 TBX1 CHD7 SLC25A15 BBS1 NDUFA11 CD96 ALG9 IL12A TNFRSF13B CD28 MLH1 MPC1 RPGRIP1L JAM3 IL7R LZTR1 APPL1 MECP2 IL2RG PRPS1 CIDEC TG PHKG2 DDOST BBS1 POU1F1 ND4 CNTNAP2 WDR19 PARN EOGT TSC1 TRIM37 PEX10 HMBS CTCF C8ORF37 PRKAR1A NPHP1 SPTA1 GPI DLD KRT18 VCP HELLPAR TRNK FASLG TSHR DYNC2I2 GATA6 GABRD ADK SLC20A2 PIEZO1 AGPAT2 PEX10 PEX6 AKT2 CTLA4 COG4 GALT NDUFB9 CSPP1 PHKA2 HBB ITK RNASEH2A KIF20A CBS SUMF1 APOA1 HLA-DRB1 TRNV MPI CD27 UGT1A1 DPAGT1 SLC25A19 CLCN7 CD46 TNFSF12 PSAP RRAS PLPBP IFT172 WDR19 SLC4A1 LACC1 PDGFRL IFIH1 TRHR GALE TNFSF15 APC NDUFS7 PRKCD PNPLA2 TGFB1 IDUA EFL1 NOS3 LIPA NUBPL SNX14 NHP2 DYNC2LI1 CCDC47 LIMK1 LBR CPT2 PDX1 PSAP HNF1A CPOX FANCL EPB42 TERT CD79A SURF1 SLC22A5 LYZ IL36RN ATP11C ND2 KLF11 COG7 LIG4 ARL6 ELN APOA1 CTSK SPTB RELA DPM2 PRKAR1A ERBB3 PCCB CEP55 TJP2 GBE1 RRM2B ABCC2 UGT1A1 CD81 ATP6V1B2 ZAP70 WRAP53 ADA2 MYRF MRPL44 HAMP EPB41 FGFRL1 KLF1 PHKB CLCA4 SAA1 HADH CP BTK ABCB4 ALG2 TERT NDUFV2 TNNT2 PRKCSH HBG2 ERCC8 PHKG2 PEX6 SPINK1 ACVRL1 TNFSF11 IFT172 ATP8B1 LIPE TNFRSF13B PALLD HLA-B CDKN2A MPV17 FADD GCLC CTLA4 NLRP3 KRT18 NDUFB11 CYBC1 PRSS2 VPS33A CA2 HSD3B7 UGT1A1 MYD88 DOCK6 PEX1 AGL GYS2 DZIP1L MAN2B1 GPC4 TIMMDC1 NDUFAF8 NDUFB10 CLDN1 IL21R TMEM70 FASLG ASL PLAGL1 SMAD4 CYP7A1 LMNA CORIN SLC40A1 AP3D1 PEX1 AGGF1 RPGRIP1L LARS1 NOD2 ARVCF DLL4 BPGM RAG2 KIAA0586 INVS COG1 H19-ICR B9D1 FOXRED1 LRPPRC TGFB1 INPPL1 SKI TNFSF11 XIAP RBPJ VPS33B XPR1 HBG1 ABHD5 UBR1 TRIM28 NDUFAF4 FOS IL2RG NR1H4 HFE F5 CLCN7 FAS GNPTAB RNASEH2B GBA IGF2 TRAF3IP1 PPARG RFXAP UBE2T DHDDS MET GLRX5 VPS45 ATP8B1 APOE ANK1 PEX1 PEX16 PPARG SOS2 SLC2A1 TMEM216 ARSA HADHA CDKN2C NAGS PEX11B PEX6 PCCB TTC21B PEX14 PEX5 MYH9 CAV1 ATP8B1 SPIB PRF1 PEX19 RFC2 ERCC4 IL2RG REST MMAA PEX12 KRT16 CLCN7 NCF2 BBS10 SRP54 IDUA MCCC1 STEAP3 STN1 NSD2 ERCC4 ACOX1 PCK2 BBS9 SDHA LMNA GALK1 NLRP1 SCNN1G BBS2 TCIRG1 PEX6 XK BCS1L CASR SLC25A15 FUCA1 SKIV2L GLB1 JMJD1C COA3 G6PC FERMT3 GNAS HBB STAT6 NEUROD1 LZTFL1 PEX5 TNFRSF13C SCYL1 PKD2 SPTB UCP2 TRIP13 PSAP DNAJB11 BRCA2 NELFA SLC25A13 TBX1 CTRC JAK3 CTNNB1 MYPN IDS SBDS LMNA ITCH BRCA1 PCSK1 CSPP1 WDR35 CCDC115 DPM1 CYBB IDUA HOXD13 TCTN2 CR2 GAA FECH ALMS1 ETFDH JAK2 CARS2 BMP2 ELN GNMT HJV PNPLA6 MKKS AHCY SMPD1 NDUFAF2 COX15 PLEKHM1 GATA6 KCNQ1OT1 LMNB2 RNU4ATAC RMRP ABCB4 DDRGK1 PIK3C2A CAV1 RNASEH2C TMEM67 POLR3A CPT2 IL17RA SF3B1 TRNW TBX1 CPT1A HNF4A MMEL1 DCLRE1C PSMB4 JAK2 CIITA TET2 ARL6 POMC ALG6 TRAF3IP1 PIGS CEP290 STOX1 COX20 IRF5 TMEM67 USP9X INTU GBA NGLY1 MFN2 SPECC1L SEC24C BSCL2 TRMU IARS1 CTNS PEX3 COG2 FAS SLC2A1 H19-ICR TMEM107 HAMP SAR1B FGFR2 HADHB HNF1B PEX2 TRMT10C XYLT1 SLC25A4 FLNC SON TNFRSF1B GPC3 ACADM RAG1 TNFRSF1B CEP120 TTC8 FANCE GBA CYBA CBL UGT1A1 SDHB TERT NPHP3 SCO1 NDUFAF5 HNRNPA1 NOTCH2 MET TMEM67 SPTB PGM1 G6PC3 PEX19 SLC25A13 NOP10 MPI IFT80 SEC63 RFWD3 PDGFRA SPRTN TRNE IGF2R SCNN1A ALG11 CD19 PPARG WDR35 TREX1 PARS2 CPT2 SLC39A4 HADHA LHX1 HBB IGHM TTC7A PET100 ABCA1 HNF4A CPA1 GNE SLC29A3 INSR COG8 HADH RFT1 PEX26 SCARB2 HFE DYNC2I1 GNS APOB PEX5 ACVRL1 SLC25A20 CD19 RRM2B TUFM BSCL2 DCTN4 ABCB11 PEX10 BLK BLVRA CYC1 FANCF HNF1B SAMHD1 PEX26 IFT140 AKR1D1 FGFR2 CFTR CC2D2A BRCA2 MAN2B1 ACOX1 NRAS CEP290 MYORG RFXAP CYP19A1 RHBDF2 HBA1 TTC37 CD28 MCM4 CCND1 FARSB FANCG NPC2 TF RERE NRXN1 IL7R TMEM67 PTRH2 MLXIPL KCNJ11 ALDOB LETM1 ATP6 CYP27A1 PEX12 PLIN1 FANCI RPGRIP1L SLC13A5 HBG2 ABCC8 IKZF1 PEX13 APOE PIGA ZAP70 ABCC2 NRAS NKX2-5 PNPLA2 APOC2 SPTA1 TFR2 KRIT1 NSMCE2 RTEL1 EWSR1 SLCO1B3 ATP6AP1 ND1 SLC11A2 SNX10 PEX26 ABHD5 CBL RPGRIP1L ETFA TNPO3 SLC29A3 NPHP3 PKD2 PEX2 ERCC4 TRNN FBP1 NEK8 LRRC8A IER3IP1 SHPK ACAD9 ADAMTSL2 ABCC8 SLC25A13 MRPS7 TRAF3IP2 RMND1 ADA CEP290 FAN1 FAM111B SLC4A1 LBR VPS33A TANGO2 NOTCH2 DYNC2H1 MLH1 TWNK PEX3 PKHD1 BICC1 RHAG PROP1 GNE ETFB ENG GANAB PEX14 INPP5E SC5D YARS2 RBCK1 GTF2I CD247 MVK CEP83 FLI1 LIPT1 GDF2 BMPER KIF23 ANKS6 CASP10 TSHB XRCC4 MMAB KCNN3 RASA2 CA2 ATP7B DNASE1L3 DHCR7 HJV B9D2 IFNGR1 RASGRP1 PEX6 ANTXR1 CIITA COG5 NPM1 SLC37A4 SLCO1B1 LDLRAP1 SLC25A19 POLG2 ALAS2 SLCO1B1 POU2AF1 DNAJC21 COX4I2 SKIV2L SOX10 SCYL1 MUC5B VPS13A MPL COX15 SLC25A13 WT1 HNF4A TP53 TKFC HEXB LMNA TWNK KLF1 VIPAS39 CYBA ABCG5 SRP54 PAX8 PTPN3 CD79B GATA2 TERC SERPINA1 LPL LONP1 KRT17 SRSF2 PTPN11 CYP27A1 KRAS IYD NCF2 NDUFAF1 FANCC FBXL4 GFM1 DLL4 PEX13 WHCR DNAJC19 NLRP3 GUCY2D TBL2 POLD1 HMBS SLC40A1 PEX14 TREX1 PEPD HBA1 TMPRSS6 RBM8A CEP19 AP1S1 PEX3 ACADVL CDKN1B IGF2 CD70 CEL DPM2 RFX6 DGUOK TCF3 ND2 TNFRSF1A CC2D2A CYBB PIK3R1 IL1RN NOP10 DNAJC21 HADHA LIPA TNFSF12 AP1B1 CDAN1 SDHA LYST BBIP1 NHP2 TMEM231 PEX16 PEX3 IL7R HPGD EIF2AK3 BTK ENG CD55 CASP8 IDUA TKT USB1 ZMPSTE24 KRT6B PTEN CLEC7A SMAD4 BTD KPTN RFX5 BCHE AMACR PEX14 TALDO1 DKC1 ALDOA JAM2 FECH GUSB AP3B1 TET2 JAK2 FUCA1 FDX2 KRAS
HP:0001903: Anemia
Genes 751
STIM1 KMT2D SMARCAL1 NDUFS1 LIPT1 ATRX TCIRG1 MPLKIP NHEJ1 RAG1 BIRC3 CDIN1 CPOX RPS28 FANCL EPB42 TERT NPHP4 STK11 STAT5B STAT3 ATP11C PTH1R KCNN4 RPS27 LAMA3 AMMECR1 ITGA2B OSTM1 NDUFS8 CTSK CD59 CASP10 GSS SPTB MLX TERT RPL5 RPS10 BRIP1 ERBB3 PCCB ECHS1 KCNQ1 NDUFS7 ATRX ELANE CD81 PNP RAG2 WRAP53 ADA2 TYMP EPB41 KLF1 TRNT1 HBD MTRR CP TERT GLA DBH LAT LRBA PIEZO1 RHAG ND4 TTC7A MAD2L2 PET100 HBG2 GATA1 NDUFAF2 IREB2 SMARCD2 SRD5A3 PHGDH CFH ACVRL1 TNFSF11 AGXT TNFRSF13B HLA-B TRNQ FAM111A RUNX1 LPIN2 BCOR GCLC CFI MPIG6B CTLA4 NLRP3 SLC7A7 HPRT1 SCO2 NDUFS2 GBA RNF113A CFI IRF2BP2 ALAS2 TF GSR PLEC XRCC4 VPS33A CA2 MYD88 PKLR GBA TRNW MYSM1 SFXN4 SLX4 PCCA GP1BA DHFR CD46 COL7A1 PFKM CASK FASLG COX3 CD3G COX8A HAVCR2 GATA1 STX11 SLC19A2 DAXX AGGF1 LIPA LARS1 MARS1 NOD2 RPS28 NUMA1 BPGM RAG2 PSMB8 FANCA TFRC CLCN7 WFS1 AK1 GLA HBA1 FANCB RPL11 LYST NDUFV1 RAG1 TPP2 COL17A1 COL4A1 LAMB3 TNFSF11 XIAP HBG1 FOXRED1 TEK XRCC2 CISD2 CLCN7 PTPN22 MMP1 TNFAIP3 FAS SPP1 OCRL UBE2T SDHA UNC13D SRD5A3 ALX4 GLRX5 TINF2 RHAG DCLRE1C VPS45 TRNS1 NPM1 ANK1 ABCA1 SLC2A1 TRNH FANCB SLC4A1 CTC1 SLC19A3 HBB HBB CP TBCE SEC61A1 ICOS PRF1 LPIN2 FANCM ERCC4 FCGR2B FANCE SNX10 WIPF1 COX6B1 MMAA MTR CTLA4 LMBRD1 HBB SRP54 IDH1 COX14 STEAP3 ATP7B MUC1 NDUFA12 HBA2 ALAD STIM1 NABP1 NLRP1 COG6 IFNG STAT4 SLC4A1 TCIRG1 LYRM7 RPS14 WAS CASR RMRP CLCN7 KCNN4 PLEKHM1 COA3 FANCL RPL5 TRNT1 ERCC3 FERMT3 RPS27 RPS7 FOXP1 HBB PKLR SMAD4 CALR GSS CFH UMPS SPTB DKC1 EPO STEAP3 BRCA2 LAMC2 TNFRSF4 ZBTB24 COX1 CRIPT TBL1XR1 CCND1 NSUN2 WFS1 CFHR1 SBDS MMP1 ND5 STK11 COL7A1 RPL35A HBB ACD BRCA1 RPS29 IRAK1 ATRX TMPRSS6 HBA1 ND6 TERT G6PD FECH RMRP TARS1 FANCG IL2RB JAK2 COX15 CAT HMGCL BMPR1A MAD2L2 GREM1 RPL35 RPS17 ALAS2 SMPD1 FOXP3 LCAT KRT14 PLEKHM1 LARS2 NDUFA10 RMRP PRKCD SLC4A1 TALDO1 ADAMTS13 ACAD8 PRDX1 ABCA1 RFXANK TGFB1 ALPL SF3B1 HK1 MTFMT TERC RECQL4 RPL35A ABCB6 HBB DCLRE1C PSMB4 CIITA NDUFA2 TET2 RPS26 COX2 NDUFAF3 COX20 RPL31 RPL15 CR2 SLC4A1 IL2RA UMPS HPRT1 SLC7A7 NDUFA4 NT5C3A NFKB2 PEPD FAS SLC2A1 HAMP MMUT LAMB3 NBN NDUFA9 MTRR GATA1 ALG8 PRKCD CTC1 MMADHC RPL27 DNM1L ACTN4 COL7A1 SLC25A21 TRNL1 NPHP1 COL7A1 PALB2 STAT1 EPB42 ATRX RAG1 ITGB4 ABCB7 HBA2 ASAH1 OPA1 ABCB7 MYSM1 FANCE GBA KCNE1 CBL SDHB KIT SCO1 NDUFAF6 RPS24 TMEM67 SPTB SPTB SLC46A1 GATA1 G6PC3 NPHP1 NDUFB8 NOP10 UBE2T RFWD3 PDGFRA PGK1 POLG ZBTB20 TACO1 TRNF ATRX BRCA1 NDUFA13 YARS2 SURF1 SLCO2A1 EPB41 HBB TBXAS1 ETV6 TTC7A PET100 SAMD9 PTEN LAMA3 RPS26 GTF2H5 PML SLC29A3 PIGT F2 HBG1 GNA14 PRF1 SCARB2 COQ2 RPL26 HYOU1 PUS1 RPS29 PHGDH GCLC TNFRSF11A UROD SDHC ACVRL1 CBLIF MALT1 UROS ND1 ELANE CD19 RRM2B ORAI1 GPX1 TSR2 CD40LG IFT140 PLA2G4A CAD FANCF COX10 RPS10 HBA1 THBD HBB-LCR ABCG8 FAM111A GATA1 GTF2E2 TCN2 BCL10 NRAS PSAP TNFRSF13C PGK1 PLEC FANCC RFXAP HBA1 LIG4 FARSB FANCG TF RPS24 COG1 ZBTB16 IL7R COA8 HELLS ANK1 RPS7 KIF1B HMGCL ANK1 TINF2 NDUFAF5 SP110 CFB FARS2 HLA-B RPL27 FANCI NHLRC2 SPTA1 HBG2 IKZF1 RPL15 FAS FANCD2 TPI1 MMACHC ZAP70 RARA TCIRG1 TP53 RPS15A MTHFD1 SPTA1 ADA TFR2 DNMT3B DGKE RTEL1 ABCD3 TRNS2 EWSR1 SLC11A2 SNX10 AK2 FIP1L1 ISCU ASXL1 SAMD9L PNP PNPO F8 TRNN SLC46A1 TREX1 GYPC UBR1 GBA SHPK SMAD4 PFKM SLC25A13 COA8 EFL1 SBDS ADA SLC12A3 MVK PIGA FMO3 REN BMPR1A SLC4A1 RAD51 AASS VPS33A GALT FOXP3 TACO1 MMUT KIT FANCD2 RHAG RPS15A ACVR1 PCNT SBDS ENG PSMB9 C3 LIG4 BMPR1A YARS2 TRNS1 NFKB1 PRKAR1A STAT1 PRKACG FLI1 GDF2 TET2 KIF23 RAG2 WAS CASP10 MECOM RTEL1 LAMC2 MMAB PNPO NDUFV2 CA2 ATP7B APC KIF15 CLCNKB MS4A1 IFNGR1 IL12B IRX5 RASGRP1 RAG1 TET2 ITGB3 NPM1 SURF1 RPL18 AIRE HBB PTF1A SEC23B CDCA7 UQCRFS1 ALAS2 BMPR1A DNAJC21 UROS COX4I2 CLPX DKC1 STAT3 RPS17 MPL EPHB4 TSR2 HMOX1 WT1 SPTA1 GBA RAD51C PACS2 TKFC HBB BTNL2 DNAJC19 ADAR ENG SH2D1A THRA KLF1 ITGB4 HBA2 GATA1 TRNW COL7A1 PGM3 SPTA1 SRP54 FTCD ELMO2 ERCC2 PDHA1 CHD7 TERC ABCD4 HBB SAMD9L ADA2 HSPA9 SRSF2 SMARCAL1 PHF21A IGH ERCC6L2 IL2RG NFKB1 HBB PHKG2 STING1 NDUFS3 NDUFS2 FANCC NDUFS4 EXT2 CUBN DNAJC19 PARN IDH2 SLC40A1 NLRP3 SMAD4 SPTA1 GPI RPL35 HBA1 RBM8A DNASE1 HELLPAR FASLG TERC DDX41 HBA2 FERMT1 PIEZO1 DNAJC21 PUS1 TNFSF12 FANCA PHKA2 HBB ITK CDAN1 SDHA LYST APOA1 NHP2 HLA-DRB1 RPS14 SLC25A38 NBN PARN NPHP4 CLCN7 RPS19 CD46 TNFSF12 HPGD BTK SARS2 ENG CD55 SLC4A1 USB1 SLX4 TBXAS1 RPL11 SMAD4 MPL RFX5 PRKCD STIM1 SLC19A2 RPS19 TGFB1 TALDO1 FCGR2A DKC1 RPL26 KDM6A ALDOA GATA1 FECH TINF2 PGM3 CFHR3 EFL1 TET2 TET2 HBA2 FDX2 KRAS
Protein Mutations 4
C282Y C677T H63D V617F
HP:0001871: Abnormality of blood and blood-forming tissues
Genes 1909
KRT14 BAP1 SMARCAL1 PRSS1 KCNJ1 TCIRG1 NHEJ1 MTAP RAG1 AMMECR1 ARHGAP31 MVK PTH1R RNASEH2C EPCAM NF1 CASP10 ASAH1 FLI1 NDUFS7 GPR35 DYNC2LI1 RAG2 STAT3 HBD MPL TERT DMD GLA LAT CCR1 PIEZO1 RHAG TTC7A HAX1 IREB2 VPS13A F5 FAM111A MPIG6B CALR FHL2 INS GBA ICOS CFI ALAS2 GSR XRCC4 KIT HPS4 GBA BCL2 MRAS SLX4 GP1BA DHFR LACC1 OCLN CASK JAK2 TREX1 SLC19A2 SERAC1 BUB3 LIPA KRT5 ATRX SCARB2 F13A1 AK1 GLA FANCI TNNT2 CFTR LYST CHIC2 NDUFV1 NBAS DOCK2 SLC25A11 F11 EVC2 TEK MPL MDM2 MMP1 IGHM COL5A2 MTTP WAS SDHA SRD5A3 SRP54 TNNI3 CLPB UFD1 NUP214 CTC1 RFXANK TBCE SDHD SEC61A1 ICOS C2 LPIN2 CD3D GPC1 FANCE PIK3R1 WIPF1 DLST COX6B1 MTR LMBRD1 HBB COX14 ATP7B EP300 DLL4 FGB BAP1 CAPN5 ANKRD11 EXTL3 TAF1A VWF HLA-DRB1 KIT WAS IL23R FANCL ERCC3 LBR FOXP1 SMAD4 CALR GSS CFH F2 ATP6V0A2 USP8 DNMT3B CAP2 LEP ADAR GP1BA IL10 IFIH1 FBN1 CRIPT DOLK MSH6 CFHR1 CREBBP SH2B3 PRKAR1A DNAJC21 STK11 PRSS1 BCR HBB RPS29 IGLL1 IRAK1 ATRX EPOR UNC93B1 ND6 DNMT3A TERT FANCG LEPR HMGCL BMPR1A MAD2L2 RPL35 RPS17 ALAS2 FOXP3 RTEL1 APC LARS2 VPS13B RAF1 MSH6 PRDX1 PRLR PEX13 ALPL MTFMT TERC TGFBR2 TERC CD244 ERMARD RFWD3 AK2 COL5A2 MAGT1 BLM NDUFAF3 RPL31 RIT1 RPL15 SLC4A1 ACAD9 TCF4 CLDN1 ADA CYB5R3 HLA-DRB1 BCL11B MMUT PTPN22 MTRR GP6 PRKCD KIF1B BRCA2 PALB2 F5 CST3 ASAH1 NLRP12 ABCC8 KIT PRDM5 ACSL4 VHL SC5D SDHB PMS2 PIGM A2ML1 POLG ABCC6 TACO1 SDHB TGFB3 RARA TRNF PIGL PDCD10 C4A VHL SPATA5 PIGT TP53 HBG1 PLOD1 HLCS HYOU1 CALR TNFRSF11A UROS ORAI1 GDNF RREB1 IFT140 CAD SDHC RUNX1 STT3B LBR HOXA11 AKR1D1 SMPD1 RFT1 RPS10 HBA1 PRDM16 MMUT ABCG8 FAM111A ALG12 GATA1 TCN2 KRT5 USP18 MSH2 HTRA2 PEX19 ITGA2 BLM ZBTB16 CTPS1 COA8 TMTC3 HELLS MAN2B1 RPS7 RASGRP1 FLT1 RECQL4 SP110 HLA-B APP FAS TPI1 MMACHC TMEM165 SLFN14 AEBP1 MTHFD1 F13A1 PTPN22 SEMA4A ATP6V0A2 KRT14 BCL11B TCF3 TRAF3 ASXL1 SAMD9L TRAF7 SDHA ATP7A CBFB F8 TREX1 UBR1 GBA SMAD4 PFKM GP1BB NEDD4L CYP4F22 CYP7B1 PIK3CA SBDS SLC12A3 MVK ICOS GNB1 GFI1 REN RAD51 GALT TAZ TACO1 IGH PEX11B HLCS PCNT PSMB9 COL3A1 SLC17A5 C3 LIG4 TRNS1 NFKB1 BMPR1A TET2 RAG2 MFAP5 SLC2A1 EPG5 RTEL1 LAMC2 NDUFV2 APC XIAP PSEN2 RAC2 CLCNKB MS4A1 LOX NUTM1 RAG1 ETV6 TET2 ITGB3 APP SPARC SCN5A STAT4 MMADHC PALB2 GFI1B UQCRFS1 STXBP2 TGFB3 CBS UROS ITGB4 DKC1 PLAT COL4A1 ADAMTS3 APC RAD51C HBB CDH23 SCN9A ENG SH2D1A SDHB HBA2 GATA1 CDC42 TBX1 MPL CALR MLH1 ITGA2B IL7R LZTR1 APPL1 COL14A1 IGH GGCX IL2RG ENG NFKB1 KIF11 PHKG2 DDOST TINF2 MGAT2 PARN IDH2 SMAD4 PIK3CD GPI SERPINF2 HELLPAR FASLG HBA2 CCND1 HOXA11 CYCS GALT GP1BB KLF1 PHKA2 HBB KIT RNASEH2A CFHR1 PDE11A ETHE1 CBS HLA-DRB1 SLC25A38 NPHP4 CLCN7 SMARCE1 CD46 RRAS MAT2A CACNA1D SLC4A1 BUB1B APOB RPL11 FAT4 KDM6A CFHR3 EFL1 NHP2 EPAS1 ARHGEF1 NDUFS1 LIPT1 PDX1 PSEN1 CPOX JAK2 RPS28 TERT CD79A A4GALT NPHP4 SERPINE1 AMMECR1 NOTCH3 LIG4 CYSLTR2 NDUFS8 SH3GL1 CTSK GSS COL1A2 DPM2 ATR ELANE PRSS2 GNAQ ADA2 EPB41 FUT8 DTNBP1 NRAS SAA1 HADH DNM2 NUP214 PLG GATA1 SMARCD2 VKORC1 PHGDH SPINK1 TNFSF11 TNFRSF13B TRNQ PROS1 TP53 XYLT2 NLRP3 AGK FLT3 SH2B3 CYBC1 PRSS2 LMAN1 CST3 CA2 GNAQ MYD88 LMAN1 B2M DOCK6 MYSM1 SFXN4 KIT F2 SDHD HAVCR2 FANCF NBEAL2 F9 GP1BB CORIN AGGF1 NOD2 NUMA1 DLL4 C1R BAX SPINK5 TMPO FANCB XIAP XPR1 ABHD5 SBDS FIBP SCN10A PTPN22 HBB TNFAIP3 FAS SPP1 GATA2 CBL ELANE ARMC5 CXCR4 JAK2 HLA-DPB1 RFXAP CSF3R CLN3 TRNS1 ANK1 CARD11 ADAMTS2 SOS2 TRNH NAGS BCL10 PEX14 GNA11 CD79A IL12A PRF1 ERCC4 FCGR2B VKORC1 HAND2 MMAA SGPL1 B4GALT1 SRP54 SMAD3 STEAP3 STN1 GCDH NDUFA12 EPO ALAD LMNA NABP1 NLRP1 MTOR TCIRG1 RPS14 BCL10 KCNJ11 SLC25A15 FUCA1 SKIV2L COA3 G6PC FERMT3 RPS27 GNAS ENPP1 FGB NEUROD1 P2RY12 UMPS BRCA2 LAMC2 ZBTB24 STXBP1 CD151 COX1 GGCX CTRC TBL1XR1 CCND1 NSUN2 COL7A1 ITCH CD3E BAP1 BRCA1 ATP7A PRTN3 TMPRSS6 CISD2 DPM1 CYBB SLC35A1 HMCN1 FECH TARS1 COX15 PLVAP FLT3 F10 RAG2 TERT FKBP14 AHCY COL5A1 WDR19 FGB LCAT GATA6 ACAD8 RNASEH2C NBN PIEZO1 MSH6 BEST1 PARN PMS2 ABCB6 BUB1 PSMB4 CIITA ABCC6 COX2 RET STOX1 COX20 RAB27A LCK UMPS HPRT1 TAL2 NT5C3A TRMU FAS CYP11B1 DSG2 SLC2A1 HAMP SAR1B LAMB3 WAS GATA1 EGLN1 PEX2 STT3B NPHP1 COL7A1 STAT1 CLCN7 RAG1 RASA1 OPA1 MYSM1 GBA NFKBIL1 KCNE1 CBL SDHB SCO1 NDUFAF6 RPS24 SPTB SLC46A1 PGM1 G6PC3 RANBP2 PIK3R1 NOP10 GATA2 MPI SEC63 RBM8A MLH1 CD19 TREX1 TAZ TCAP HBB TBXAS1 IGHM PET100 SAMD9 PTEN COG4 CPA1 GCNT2 PML SLC29A3 GP1BA LPP TXNRD2 COG8 ADAM17 KIT RASGRP2 PDCD10 RFT1 PANK2 RAG1 RPL26 SLC27A4 PROS1 ASXL1 CEBPA CD19 FKBP14 BLK RAD54B SDHC FANCF AKR1D1 TGFB2 CYB5A VCL ADAMTS2 DOCK8 ATOH7 MAN2B1 HBB-LCR ERF NRAS PGK1 PLEC MYORG BCL6 MCM4 CCND1 FANCG TRAC NIPBL GATA2 ZNF469 RPS24 STAT3 IL7R ITGA2B SLC2A10 ANK1 NBN FCGR2C KIF1B NLRP3 TAZ ALDOB NDUFAF5 TUBB1 RPL27 FANCI TNFRSF1A HBG2 RPL15 ACP5 ZAP70 SLC39A13 F11 TP53 NRAS MYH7 RPS15A SPTA1 EPAS1 TFR2 KRIT1 RTEL1 EWSR1 SNX10 CBL SLC29A3 PNPO ERCC4 TRNN SLC46A1 NOTCH1 ACAD9 TSC2 ABCC6 MRPS7 MECOM FAN1 FMO3 BMPR1A SAMHD1 VPS33A FOXP3 SLC4A4 TICAM1 SF3B1 GNE TERT ACVR1 BAG3 ENG ELANE YARS2 PTPN11 CD247 MCFD2 PRKAR1A LMX1B PRKACG WAS CASP10 IKZF1 MMAB PNPO RASA2 CA2 ATP7B FOXN1 RASGRP1 CIITA FGG PRLR RNF168 SH2B3 PTF1A BMPR1A COX4I2 MPL DNMT3A C1GALT1C1 ASXL1 TSR2 EPHB2 ACTC1 TKFC THRA KLF1 ITGB4 SPTA1 SRP54 FTCD TMEM127 CD79B LRP5 TBXA2R MPDU1 HBB AAGAB ADA2 HSPA9 PIK3CA SRSF2 PTPN11 IDH1 KRAS PLOD1 ERCC6L2 SGCD HBB NDUFS3 F9 FBXL4 CUBN COL1A1 COL5A1 RPL18 NLRP3 NUMA1 PLEC TREX1 RPL35 DNASE1 ARF1 CD70 TPMT MAX BRIP1 FERMT1 KIF1B ITGB2 PIK3R1 NOP10 DNAJC21 PUS1 COL1A2 TNFSF12 CDAN1 SDHA NHP2 ANGPTL6 NBN PEX3 NDE1 SLC22A4 CD109 HPGD EIF2AK3 ENG TTN KRIT1 PTEN TET2 JAK2 TALDO1 MAP1B DKC1 RPL26 ALDOA JAM2 GATA1 USP8 PGM3 AP3B1 TET2 BLOC1S6 TET2 JAK2 HBA2 STIM1 KMT2D CASR GLB1 GDF2 ATRX TERT TSC2 CDIN1 F7 BLNK MYH7 PTEN STK11 STAT3 KCNN4 SPINK1 TCF4 RRAS2 MEFV OSTM1 CD59 CTLA4 TNNI3 PDGFRA TERT RPL5 RPS10 BRIP1 RUNX1 KRAS FOXN1 KCNQ1 ATRX CBL APOE TYMP TTC37 ABL1 ATM IGH CHD7 MTRR DOLK RNASEH2A PEX1 TERT ND4 PROC CYP11B2 MLH3 MAD2L2 MSH2 CCND1 ATP7A KCNQ1 MYD88 SRD5A3 CFH COL3A1 TCF4 PRF1 RUNX1 BCOR AKT1 DCLRE1C CFI SLC7A7 HPS3 FGA RNF113A SETBP1 IRF2BP2 TF SEMA3E PLEC CHST14 PLEC ACTN2 PKLR GINS1 TRNW TET2 PCCA PEX10 ESCO2 COL7A1 PFKM CD3G BRD4 COX8A THPO STX11 AGA DAXX C4A CYP2A6 MARS1 DES CD40 RPS28 MMACHC COL4A2 PSMB8 LAMA4 FANCA MYH9 CLCN7 RET WFS1 MST1 PEX12 DSE NCF4 RAG1 TPP2 COL17A1 RAG2 F5 SGCG XRCC2 PDGFRB SSR4 OCRL UNC13D SUFU ALX4 FYB1 TINF2 RHAG DCLRE1C SRP72 HSD3B7 IFNG ACAT1 ABCA1 PMM2 GNAS TPM1 FANCB TAL1 NF2 FAS IL2RG NPC1 HBB HBB CEP57 FANCM ETHE1 FGA SNX10 SMO CTLA4 CORO1A TONSL XRCC4 TET2 MUC1 JAGN1 DGUOK CD3E HBA2 NEBL MAP2K2 NCF1 GALC RBM20 GATA2 COG6 COMT IFNG XYLT1 STAT4 SLC4A1 GP1BA RMRP CLCN7 PRKACA KCNN4 PLEKHM1 RAB27A ERAP1 PKLR PSTPIP1 TFAM NEU1 NOTCH1 HIRA DKC1 EPO STEAP3 TNFRSF4 AKT1 FGA KLHDC8B WFS1 TGFBR1 WAS PMS1 DIAPH1 VWF MMP1 CIITA RPL35A TEK SOS1 CD8A MDH2 GSN RNF43 G6PD HLA-B CYTB RMRP FGG IL2RB SERPIND1 CAT GREM1 PAX4 KRT14 NDUFA10 BCS1L PRKCD SLC4A1 TALDO1 HNF1A RIN2 ADAMTS13 ABCA1 RFXANK TGFB1 TGFBR2 HK1 RPL35A HBB RPS20 SF3B1 RPS26 KRT5 MLLT10 NCF1 CR2 IL2RA MYC SLC7A7 NDUFA4 SLC35C1 PROC NFKB2 ANKRD26 PEPD MTHFR WIPF1 F13B SOS1 LYST NBN LMBRD1 GCK ALG8 CTC1 MMADHC RPL27 DNM1L ACTN4 ADA2 PMM2 SMAD3 TRNL1 EPB42 BMPR2 HAVCR2 ITGB4 HBA2 CHEK2 FGA CYB5R3 RNU4ATAC SPTB NPHP1 NDUFB8 CCM2 VHL ANKRD1 SERPINC1 NGLY1 PEX16 SALL4 MYBPC3 NPM1 ATRX BRCA1 ANO6 NDUFA13 SLCO2A1 EPB41 TDP2 LAMA3 RPS26 GFI1B KRT14 F2 GNA14 PRF1 PIK3CA PUS1 RPS29 NHP2 GCLC SDHC CBLIF MALT1 ND1 ELANE SDHD GPX1 MSH2 ALDOB CD40LG PLA2G4A ARFGEF2 GATAD1 NAXD LMNA CEBPE COX10 GP9 SLC2A1 THBD F5 THBD BCL10 PSAP TNFRSF13C PDGFB FANCC F8 TNNC1 LIG4 ACTA2 RNASEH2B FLNA GBA COG1 SMAD4 IKBKG PRKG1 HMGCL RB1 ANK1 TGFBR2 TINF2 SLC30A10 CFB PRF1 POMP SMPD1 LAMTOR2 NHLRC2 PDGFRB FANCD2 PTPRC TCIRG1 IKBKG ADA POLE KRAS EXTL3 CYP7B1 ABCD3 TRNS2 CTLA4 LRP5 PPCS GYPC MPL COL1A1 COL4A5 SDHD CFTR CTNNB1 COA8 ITGB3 CLPB THSD1 EFL1 FGG SRC CD247 PIGA TYROBP IRAK4 TREM2 BAP1 MMUT KIT KRT1 FAH HBG1 STAT1 MAP2K1 PTEN CRYAB KIF15 SLC35A1 ACP2 IL12B IRX5 NTHL1 SLC30A10 PIGL ATM SURF1 AIRE HBB SEC23B CDCA7 SRSF2 MEFV DNMT3A NBEAL2 RPS17 EPHB4 RFX5 HMOX1 FH NFIX GBA PACS2 PUF60 KRAS BTNL2 SMARCB1 DNAJC19 CDKN2A BRAF APP PGM3 ELMO2 ERCC2 PDHA1 TBC1D24 CHD7 TNFRSF13B CD28 CTRC LDB3 TBK1 SMARCAL1 WDR1 CSRP3 IL10RA JAK2 NDUFS2 EXT2 EOGT TSC1 ARL6IP6 SLC40A1 FBN1 AMMECR1 CTCF GP1BB SPTA1 DLD F8 CXCR4 DDX41 IL6ST SLC20A2 PIEZO1 COLGALT1 APP CTLA4 COG4 ATP6V1E1 FANCA ITK KIF20A APOA1 CD27 DPAGT1 PARN RPS19 KCNJ5 TNFSF12 RHOH NF1 SLX4 LIG4 IFIH1 MPL PLEC PRKCD STIM1 SLC19A2 CFHR3 RPS19 TGFB1 FCGR2A GNAS GUCY1A1 NEXN TP63 NOS3 LIPA BMS1 DOCK8 MPLKIP VHL BIRC3 STS FANCL EPB42 POT1 GNAS SH2B3 STAT5B ATP11C KLF11 RPS27 LAMA3 RAF1 ITGA2B LAMTOR2 IL12A-AS1 SPTB MLX PRKAR1A ERBB3 PCCB ECHS1 CD81 PNP THPO WRAP53 CTNNB1 KLF1 TRNT1 F10 CP ALG2 ITGB3 DBH LRBA PET100 F7 TNNT2 PRKCSH AEBP1 KLRC4 HBG2 SLC17A5 NDUFAF2 EVC PEX6 ACVRL1 AGXT HLA-B LPIN2 GCLC CTLA4 COL1A1 HPRT1 FADD SCO2 NDUFS2 VPS33A CYP4V2 HSD3B7 FLI1 CD46 MAN2B1 OTULIN FASLG COX3 GATA1 SDHA AP3D1 ATM LARS1 ARVCF BPGM GP1BA RAG2 NFKB2 TFRC JAK2 HBA1 RPL11 HABP2 COL4A1 LAMB3 TNFSF11 RBPJ VPS33B HBG1 FOXRED1 CCM2 CISD2 PLAU NR1H4 CLCN7 TBX2 RNASEH2B GBA UBE2T ARHGAP26 SCN11A MET GLRX5 F13A1 VPS45 NPM1 APOE BCR USB1 SLC2A1 LRP5 SLC4A1 MYH11 SLC19A3 CP MYH9 RBM10 RET NLRC4 MYPN IL2RG SRP54 RAF1 GGCX TSC1 NCF2 SLC39A13 IDH1 KIT TNFRSF13B CASP10 PTPN11 STIM1 ATP7A ELN GFI1 XK LYRM7 CASR GLB1 JMJD1C RPL5 TRNT1 FOXN1 ARPC1B RPS7 IVD HBB TTI2 TNFRSF13C NLRP3 SPTB RUNX1 CACNA1S FLNA JAK3 CARD11 MYPN SBDS COL1A2 ND5 PROC STK4 SDHB ACD WRAP53 BUB1B RYR1 SERPINF2 HBA1 VWF BCR TCIRG1 PTPN11 CR2 JAK2 PADI4 SMPD1 PLEKHM1 RAD54L LMNB2 RNU4ATAC RMRP BRAF AIP ABCC9 CPT2 FZD4 SF3B1 TBX1 CD36 CCBE1 RECQL4 HNF4A DCLRE1C JAK2 NDUFA2 MYLK TET2 ALG6 TNXB SERPINC1 CD3D FZD4 GBA GNAQ SEC24C MAX ABL1 FGFR2 NDUFA9 COL7A1 FLNC TNFRSF1B SLC25A21 ATRX ABCB7 TNFRSF1B ABCB7 ACD FANCE CYBA JAK2 TERT CAPN3 TMEM67 GATA1 SDHAF2 CD81 FKTN CHST14 UBE2T RFWD3 PDGFRA PGK1 COL4A1 ZBTB20 RPSA TGFBR3 TGFB2 YARS2 SURF1 UNC119 TMEM127 ETV6 TTC7A IDH2 GTF2H5 SCARB2 COQ2 PHGDH HPS5 UROD PEX5 ACVRL1 RRM2B CD4 TET2 TSR2 MPO FH AKT1 SAMHD1 PEX26 TRIP13 RAG1 SALL4 ITGA2B ACTN1 GTF2E2 HRG ZNF341 RFXAP RHBDF2 HBA1 MSN TTC37 CD28 CARD9 FARSB LRP5 NPC2 TF PRKAR1A C1S KCNJ11 COL3A1 FARS2 PEX12 CYB5A SPTA1 IKZF1 UBAC2 KLKB1 APOE ABCC2 RARA GFI1 LIG4 UBE2A SSR4 TCN2 NDP DNMT3B DGKE PDGFB NSMCE2 ATP6AP1 TLR3 SLC11A2 ABHD5 AK2 FIP1L1 ISCU FGB PNP PKLR TGFBR1 HLA-DPA1 LRRC8A SHPK PLN ABCC8 PLOD3 TLR4 SLC25A13 HPS6 ADA SLC4A1 LBR RAC2 AASS PANK2 MLH1 PICALM COPA ATP6V1A FANCD2 RHAG RPS15A CYP2C9 SBDS GATA1 SC5D BMPR1A RS1 MVK FLI1 GDF2 KIF23 FLNA PTEN APP MECOM MPL DNASE1L3 KCNE5 IL10 FLNA IFNGR1 NPM1 SLC37A4 RPL18 HBG2 ALAS2 INHBA DNAJC21 CYP26C1 CDC42 F8 NF1 CLPX TINF2 STAT3 VPS13A MPL RIN2 WT1 SPTA1 VPS13B GLI1 FGG COL5A1 ADAR PTPN22 CYBA TRNW COL7A1 F12 FN1 GATA2 TERC ABCD4 HPS1 PROS1 SAMD9L TP53 LBR PHF21A STING1 NCF2 SMAD3 FIG4 FANCC NDUFS4 ITGB3 PDE4D DNAJC19 SIK3 RYR1 HBA1 RBM8A CEL TERC TCF3 CYBB MYC GP9 KCNJ11 LYST RPS14 TNXB IL7R BTK BLOC1S3 SARS2 BLNK CD55 USB1 ZMPSTE24 TBXAS1 SMAD4 MYH6 RFX5 GLB1 AMACR FOXE3 SPATA5 VHL MCFD2 F13B FECH TINF2 COL3A1 FDX2 KRAS
Protein Mutations 3
C282Y H63D T315I
HP:0000819: Diabetes mellitus
Genes 528
PLIN1 ABCC8 CASR PRSS1 ELMO2 LIMK1 SOX3 PDX1 SLC2A2 PDX1 PDX1 HNF1A HYMAI SPINK1 GNAS COX1 REEP6 PRPF6 STAT3 ND2 SPINK1 KLF11 KIAA1549 WRN KCNJ11 LIG4 ARL6 EDA2R ELN KCNJ11 FOXH1 WFS1 PWAR1 HMGA1 RRM2B GPR35 LIPE PRSS2 WRAP53 STAT3 HAMP TRNC PPP1R3A ATM PAX4 MMP14 RDH12 CP ZNF408 BRAF TRNK TRNL1 ND4 TTC7A NDUFS3 NDUFV2 AEBP1 SPINK1 PSTPIP1 HMGA2 LRP6 LIPE PALLD TCF4 TRNQ CDKN2A TRNK TTPA INS NDUFB11 GJA1 PAX4 CEL PTCH1 PRSS2 XRCC4 BSCL2 SLC7A14 LMNB2 BBS2 PALB2 INSR TIMMDC1 NDUFAF8 NDUFB10 SIX3 AGBL5 WRN GAS1 COX3 PLAGL1 TREX1 PDX1 SMAD4 SLC19A2 LMNA CORIN PDE8B IL6 BEST1 CRX PRKAR1A WFS1 TGIF1 MST1 NDN GCK NDUFS6 CFTR RETN FOXRED1 RBP3 CNGB1 LIPC ZNF513 GPD2 UBR1 NDUFAF4 WFS1 FOS ABCC8 CISD2 TRNQ IFT140 HFE HYMAI IRS1 HNF4A RNASEH2B FGF8 ARMC5 APOA5 LEMD3 DCAF17 PPARG EDA TP53 DCAF17 AGPAT2 GLRX5 OFD1 TINF2 TRNS1 MAGEL2 APPL1 MAPK8IP1 ARL6 GTF2IRD1 PPARG TRNH NDUFS8 NDUFAF3 TDGF1 CDHR1 SNORD115-1 ZFYVE26 TMEM126B CP IGF2BP2 PTPN22 CAV1 CNGA1 DHDDS RFC2 KIZ MEN1 HBB XRCC4 TRNW PRPF8 FOXP1 ABCC8 LMNA NEK2 SNRPN LMNA MAK FGFR1 MMP2 CLIP2 GCK BBS2 HESX1 KCNJ11 ZFP57 PRKACA GLIS3 HNF1A VANGL1 NDUFS2 NEUROD1 NDUFV1 ABCA4 C8ORF37 TRNS2 DMPK LEP BRCA1 ADAR IFIH1 GCK CERKL NRL COX1 CTRC INS GJB4 WFS1 AIP RAC1 GJB3 SBDS ND5 PTF1A LMNA ITCH PROM1 PRSS1 PIK3R1 NEUROD1 HBB GCK CISD2 ND6 IMPDH1 TERT LEPR ALMS1 BRCA2 PRCD BMP2 CAT ELN KCNJ11 TRNL1 PNPLA6 PAX4 NDUFAF2 FOXP3 GATA6 PRPF4 PLAGL1 NODAL HNF1A CA4 TUB CAV1 RNASEH2C TTC8 POLR3A PIK3R1 NR2E3 HNF4A NDUFB3 POLA1 PWRN1 PRKACA PCARE AR INSR COX2 STOX1 IL2RA PDE4D BSCL2 HGSNAT CTNS DNAJC3 IGF1R KLF11 IPW GJA1 GCK DLL1 PEX10 HNF1B CTC1 DNM1L ND6 ARHGEF18 RP1 SLC25A4 NSMCE2 TRNL1 CLRN1 AHR STAT1 NDUFS7 ND1 OPA1 DNAJC3 NDUFAF5 ABCC8 AMACR NOP10 EIF2AK3 MKKS ABCC8 PPARG TRNF ALMS1 GUCA1B PDE6G CTNNB1 CCDC28B ND3 INSR LHX1 CDON APOE HNF4A CPA1 SLC29A3 DMXL2 TOPORS IDH3B NEUROG3 HFE SCAPER ND1 ARL2BP PDE6B BLK TRNE HNF1B HNF1B SAMHD1 PEX6 NEUROD1 NPAP1 COX3 GPR101 CNOT1 EIF2S3 PRPF3 IL2RA HLA-DRB1 ZIC2 NDUFS1 SPATA7 TRMT10A BLM CYP19A1 FUZ PRKAR1A CYTB PTRH2 LMNA TRNV FBN1 MLXIPL ZFP57 AIP KCNJ11 KCNJ11 KRAS FLT1 FXN PLIN1 INS WFS1 TWNK RPGR HNF4A DISP1 BLK PNPLA2 POLG MC4R POLG2 BAZ1B NSMCE2 RTEL1 TRNS2 PROKR2 ND1 PPARG NDP AHI1 SOX2 SAG SLC29A3 HERC2 UBR1 IER3IP1 KCTD1 ABCC8 CFTR CNBP CAVIN1 SLC12A3 MKRN3-AS1 FOXP3 SLC16A2 TWNK PROK2 PCNT EYS COX2 TRNF RGR GTF2I STAT1 PAX4 DHX38 IDH3A ZMPSTE24 PPP1R15B XRCC4 PTPN1 CLCNKB HJV ERGIC1 LEPR RHO SHH NPM1 ZBTB20 ATM NDUFA6 INS AIRE RP9 PTF1A TCF7L2 KLHL7 DNAJC21 AKT2 RLBP1 AKT2 TP53 PLCD1 NKX2-5 CDH23 NDUFS4 FOXC2 HNF1A LMNA LMNA MTNR1B HNF1A TRNW MKRN3 SRP54 GLI2 NDUFA1 IRS2 NDUFA11 TERC USH2A CTRC POC1A RP2 ITPR3 MOG PDX1 IFT172 APPL1 ARNT2 ATP6 ND5 SNORD116-1 CIDEC BBS1 NDUFAF1 PDE11A FAM161A RPE65 PDE4D PARN INS PRPH2 ROM1 TBL2 OTX2 POLD1 MAFA HNF4A KDSR CEP19 GCK SEMA4A ARL3 CEL LRAT HNF1A GATA6 TULP1 SNRNP200 IFT88 AGPAT2 TRNE FSCN2 TRNS1 NDUFB9 GATA3 STUB1 ENPP1 MERTK RNASEH2A KCNJ11 HLA-DQB1 NHP2 FXN IMPG2 SUFU POMGNT1 EIF2AK3 SARS2 HYMAI GCK TKT USB1 ZMPSTE24 PRPF31 HNF1B PDX1 SLC30A8 PNPLA2 SLC19A2 DKC1 PDE6A USP8 EFL1 FGFR1 CRB1 PEX1 NUBPL
HP:0000822: Hypertension
Genes 411
PLIN1 SMARCAL1 LIMK1 SDCCAG8 ELP1 TSC2 FMR1 CPOX GNAS COX1 SH2B3 LYZ CLCN2 NF1 NOTCH3 ARL6 EDA2R ELN APOA1 CTLA4 CC2D2A MLX FGFR2 ADA2 TRNC MMP14 MTRR BANF1 GLA TRNK TRNL1 CCR6 GPC3 CYP11B2 ERCC8 TRIM32 CFH ACVRL1 COL3A1 LRP6 TRNK XYLT2 CFI CALR ITGA8 SLC37A4 SUGCT GBA NF1 CD46 WT1 WRN KLHL3 BBS4 THPO SDHA POU6F2 ABCG8 CORIN NFIX PDE8B NOD2 ARVCF INVS PRKAR1A RET GLA SLC25A11 SCNN1A TRIM28 TRNQ OFD1 B2M WT1 TNFRSF11B ARMC5 FGFR2 HLA-DPB1 PPARG EDA TP53 BNC2 ALX4 LMX1B NPHP1 ACAT1 ACTA2 GNAS GTF2IRD1 SDHC UFD1 ENPP1 GATA5 LEMD3 MYH11 HGD SDHD RET RFC2 IRF5 KCNJ5 LDLR ERCC6 DLST REST CAV1 GANAB BBS10 SMAD3 TET2 TRNW MUC1 POU3F4 OFD1 ADA2 SDHB ERCC4 BBS9 CD2AP LMNA CYP11B1 MEF2A MMP2 CLIP2 COL4A3 ELN COMT HPSE2 BBS2 XYLT1 PRKACA JMJD1C SMAD4 VANGL1 G6PC WNK4 DIS3L2 TMEM70 HBB ENPP1 MAFB LZTFL1 TRNS2 PKD2 USP8 HIRA TRIP13 DNAJB11 FBN1 TGFBR1 CFHR1 SH2B3 PKD1 LMNA PRKAR1A SDHB SCN2B PRTN3 NR3C2 WDR35 MDH2 DNMT3A ELP1 ALMS1 ELN TRNL1 IQCB1 RET MKKS YY1AP1 LARS2 AIP TBX1 TGFBR2 SPRY2 FBN1 NOTCH1 ABCB6 PRKACA MTTP MYLK ARL6 ABCC6 TRAF3IP1 COL5A2 RET STOX1 H19 LEMD3 FGA TMEM67 SEC24C MAX CYP11B1 SLC25A11 ND6 KIF1B ACTN4 ADA2 HSD11B2 DYRK1B NPHP1 BMPR2 PDE3A ND1 TTC8 JAK2 MGP NOTCH2 VHL SDHB SDHAF2 VHL MYMK NPHP3 ABCC6 TGFBR3 PPARG ALMS1 SMAD6 TRPC6 CCDC28B TMEM127 VHL TNFRSF11A SCNN1B BBS5 SCNN1B ARHGAP31 APOB SDHD SDHD PDE3A GDNF RREB1 CYP11B1 ECE1 TMEM237 TRNE SDHC FH YY1AP1 LMNA TGFB2 COX3 GPR101 CYP17A1 BRCA2 THBD LMX1B WNK1 LRIG2 FIG4 CEP290 HLA-DRB1 XPNPEP3 CCND1 MKS1 ACTA2 FUZ COL4A3 CYTB SMAD4 LMNA TRNV SLC2A10 FBN1 PRKG1 COQ7 MLXIPL KIF1B AIP FLT1 SERPINA6 CFB PLIN1 HLA-B NKX2-5 WT1 PKD1 EGFR MC4R EPAS1 SLC2A10 GCH1 BAZ1B NSMCE2 VHL PCSK9 KRT8 WT1 WDPCP TRNK PKD2 APRT HLA-DPA1 MPL COL4A5 KCTD1 SDHD TRIM28 GP1BB THSD1 BBS12 CEP290 FMO3 CYP21A2 CUL3 NPHP4 PKHD1 BICC1 COL4A4 BSCL2 NR3C1 WT1 GANAB C3 COX2 TRNF IFT27 GTF2I STAT1 SDCCAG8 PAM16 MFAP5 LOX IL12B SLC37A4 LDLRAP1 MYH7 BBS7 TGFB3 CBS ARMC5 CEP164 ADAMTSL4 INVS CDH23 COL5A1 CACNA1D LMNA PTPN22 SCNN1A SDHB ABCG5 TBX1 FN1 TMEM127 BBS1 CYP17A1 FN1 RPGRIP1L AIP PHF21A CACNA1H POR ND5 ENG BBS1 PDE11A EXT2 COL1A1 GUCY1A1 TSC1 FBN1 TBL2 HMBS HMBS C8ORF37 NR3C1 FOXF1 PRKAR1A NPHP1 CEP19 KRT18 MAX ABCC6 VAC14 KIF1B KCTD1 TRNS1 HSD11B2 GJA1 SCNN1G KCNJ5 BBIP1 PDE11A ANGPTL6 CDH23 KCNJ5 MAT2A SMAD4 IDUA IFT172 CACNA1D WDR19 ZMPSTE24 CYP11B1 FOXE3 CCN2 GNAS SCNN1G GUCY1A1 NFU1 VHL USP8 CFHR3 NOS3 COL3A1 JAK2 OSGEP
HP:0002721: Immunodeficiency
Genes 268
PIK3CA CCDC47 CTBP1 ATRX NHEJ1 BLNK CHD1 CD81 NOP10 IKBKB CD79A TNFRSF13C CD19 AICDA LIG4 CD19 IRF2BP2 LAMTOR2 IFNGR1 UNC119 IGHM TTC7A CD81 PNP SPATA5 RAG2 PKP1 WRAP53 ADA2 TTC37 FGFRL1 CLCA4 TERT RAG1 HYOU1 LAT TYK2 LRBA TTC7A NFE2L2 CD19 DCTN4 RREB1 CD40LG FRAS1 IKBKG TNFRSF13B CFTR RAG1 IRAK4 MAN2B1 CTLA4 JAK3 SHANK3 AGL IL21 ICOS PRKDC TNFRSF13C XRCC4 LIG4 CARD9 BSCL2 TBCE CTPS1 IL7R ANTXR2 MAN2B1 HELLS IL21R MALT1 CD3G LAMTOR2 AP3D1 CD40 ARVCF MBTPS2 ACP5 PTPRC NFKB2 TFRC MS4A1 MAPK1 MTHFD1 LYST ADA POLE RAG2 XIAP SDHC DNMT3B UNG BCL11B DOCK2 ORAI1 RTEL1 IL12RB1 TLR3 FOS AK2 IL2RG TRAF3 CTLA4 DCLRE1C SIN3A SLC46A1 LRRC8A AGPAT2 TINF2 DCLRE1C IRF7 GP1BB TGFB1 UFD1 PPARG LETM1 CAVIN1 ADA ICOS SP110 CD247 IL2RG IRAK4 RAC2 ICOS MMUT TICAM1 KLLN PIK3R1 WIPF1 NFKB1 RBCK1 CORO1A IRF8 STAT1 XRCC4 MEIS2 EPG5 RTEL1 ZBTB24 IKZF1 NSD2 XIAP EXTL3 NCF1 STIM1 FOXN1 MS4A1 GATA2 COG6 CRKL ISG15 COMT RAG1 NPM1 ATM WAS HBB RNF168 RMRP SKIV2L CDCA7 JMJD1C STAT1 CHD1 FOXN1 PRPS1 RAB27A CDC42 UROS BCL10 SKIV2L DKC1 TNFRSF13C DNMT3B FCGR3A HIRA DKC1 ACTB BCR TNFRSF4 ZBTB24 CDH23 SH2D1A CPLX1 CYBA PGM3 CDC42 SEC23B STK4 TBX1 CD3E CD79B CHD7 POLE ACD IGLL1 TERC IFNGR2 TNFRSF13B CD28 UNC93B1 STX1A EPG5 AKT1 TBK1 SMARCAL1 TERT CR2 IRF8 RMRP IL2RG IL12B IL2RB NFKB1 NCF2 RAG2 WHCR PARN RTEL1 SIK3 SDHB LMNB2 PIK3CD CARD11 FCN3 CAV1 TBX1 TCF3 CYBB PIK3R1 CR2 USF3 PTEN MYC TNFSF12 AK2 MAGT1 CR2 IL2RA LCK RNF168 CD3D NHP2 IKBKG SEC24C PARN NFKB2 IL7R TNFSF12 BTK LYST CUL4B USB1 BUB1B PRKCD CTC1 SPATA5 DKC1 STAT1 GATA1 TINF2 USP8 RAG1 PGM3 TNFRSF1B SDHD MYD88
SNP 0