Little is known about efficacy of switching to tenofovir monotherapy for lam-resistant chronic hepatitis B patients who achieved a complete virological response to lamivudine plus adefovir. This study was to investigate the efficacy of switching to tenofovir monotherapy for lamivudine -resistant chronic hepatitis B patients with undetectable hepatitis B virus DNA while on lamivudine plus adefovir combination therapy

NCT03236584

Conditions

1. Proportion of Patients With a Sustained Virological Response (Serum HBV DNA
2. Proportion of Patients With a Sustained Virological Response (Serum HBV DNA <
3. Proportion of Patients With a Sustained Virological Response (Serum HBV DNA <20 IU/mL) at Week 48

Interventions

1. Drug: lamivudine plus adefovir combination
2. Drug: Tenofovir Disoproxil Fumarate

MeSH:Hepatitis B Hepatitis B, Chronic

Inclusion Criteria: - HBsAg (+) for > 6 months age >19 years antiviral resistance to LAM (rtL180M and/or M204V/I) currently receiving LAM plus ADV for more than 12 months HBV DNA levels <20 IU/ml on two consecutive tests of 3-month interval Exclusion Criteria: - Cr ≥1.5 mg/dL Evidence of decompensated liver disease Malignant neoplasm Coinfection with HIV, HCV Inclusion Criteria: - HBsAg (+) for > 6 months age >19 years antiviral resistance to LAM (rtL180M and/or M204V/I) currently receiving LAM plus ADV for more than 12 months HBV DNA levels <20 IU/ml on two consecutive tests of 3-month interval Exclusion Criteria: - Cr ≥1.5 mg/dL Evidence of decompensated liver disease Malignant neoplasm Coinfection with HIV, HCV Proportion of Patients With a Sustained Virological Response (Serum HBV DNA Proportion of Patients With a Sustained Virological Response (Serum HBV DNA < Proportion of Patients With a Sustained Virological Response (Serum HBV DNA <20 IU/mL) at Week 48 Hepatitis B Hepatitis B, Chronic null --- M204V ---

Inclusion Criteria: - HBsAg (+) for > 6 months age >19 years antiviral resistance to LAM (rtL180M and/or M204V/I) currently receiving LAM plus ADV for more than 12 months HBV DNA levels <20 IU/ml on two consecutive tests of 3-month interval Exclusion Criteria: - Cr ≥1.5 mg/dL Evidence of decompensated liver disease Malignant neoplasm Coinfection with HIV, HCV Inclusion Criteria: - HBsAg (+) for > 6 months age >19 years antiviral resistance to LAM (rtL180M and/or M204V/I) currently receiving LAM plus ADV for more than 12 months HBV DNA levels <20 IU/ml on two consecutive tests of 3-month interval Exclusion Criteria: - Cr ≥1.5 mg/dL Evidence of decompensated liver disease Malignant neoplasm Coinfection with HIV, HCV Proportion of Patients With a Sustained Virological Response (Serum HBV DNA Proportion of Patients With a Sustained Virological Response (Serum HBV DNA < Proportion of Patients With a Sustained Virological Response (Serum HBV DNA <20 IU/mL) at Week 48 Hepatitis B Hepatitis B, Chronic null --- M204V --- --- M204V ---

Little is known about efficacy of switching to tenofovir monotherapy for multidrug-resistant chronic ehpatitis B patients who achieved a complete virological response to entecavir and tenofovir. This study aimed to investigate the efficacy of switching to tenofovir monotherapy for multidrug-resistant chronic hepatitis B patients with undetectable heaptitis B virus DNA while on tenofovir plus entecavir combination therapy.

NCT03236610

Conditions

1. Proportion of Patients With a Sustained Virological Response (Serum HBV DNA
2. Proportion of Patients With a Sustained Virological Response (Serum HBV DNA <
3. Proportion of Patients With a Sustained Virological Response (Serum HBV DNA <20 IU/mL) at Week 48

Interventions

1. Drug: tenofovir monotherapy
2. Drug: tenofovir plus entecavir combination

MeSH:Hepatitis B Hepatitis B, Chronic

Inclusion Criteria: - HBsAg (+) for > 6 months age >19 years antiviral resistance to LAM(rtL180M and/or M204V/I) & ADV (rtA181V/T and/or rtN236T) or ETV (rtT184A/C/F/G/I/L/S, rtS202G, or rtM250L/V, in addition to rtM204V/I) HBV DNA levels <20 IU/ml on two consecutive tests of 3-month interval currently receiving TDF+ETV for more than 12 months Exclusion Criteria: - Cr ≥1.5 mg/dL Evidence of decompensated liver disease Malignant neoplasm Coinfection with HIV, HCV Inclusion Criteria: - HBsAg (+) for > 6 months age >19 years antiviral resistance to LAM(rtL180M and/or M204V/I) & ADV (rtA181V/T and/or rtN236T) or ETV (rtT184A/C/F/G/I/L/S, rtS202G, or rtM250L/V, in addition to rtM204V/I) HBV DNA levels <20 IU/ml on two consecutive tests of 3-month interval currently receiving TDF+ETV for more than 12 months Exclusion Criteria: - Cr ≥1.5 mg/dL Evidence of decompensated liver disease Malignant neoplasm Coinfection with HIV, HCV Proportion of Patients With a Sustained Virological Response (Serum HBV DNA Proportion of Patients With a Sustained Virological Response (Serum HBV DNA < Proportion of Patients With a Sustained Virological Response (Serum HBV DNA <20 IU/mL) at Week 48 Hepatitis B Hepatitis B, Chronic null --- M204V ---

Inclusion Criteria: - HBsAg (+) for > 6 months age >19 years antiviral resistance to LAM(rtL180M and/or M204V/I) & ADV (rtA181V/T and/or rtN236T) or ETV (rtT184A/C/F/G/I/L/S, rtS202G, or rtM250L/V, in addition to rtM204V/I) HBV DNA levels <20 IU/ml on two consecutive tests of 3-month interval currently receiving TDF+ETV for more than 12 months Exclusion Criteria: - Cr ≥1.5 mg/dL Evidence of decompensated liver disease Malignant neoplasm Coinfection with HIV, HCV Inclusion Criteria: - HBsAg (+) for > 6 months age >19 years antiviral resistance to LAM(rtL180M and/or M204V/I) & ADV (rtA181V/T and/or rtN236T) or ETV (rtT184A/C/F/G/I/L/S, rtS202G, or rtM250L/V, in addition to rtM204V/I) HBV DNA levels <20 IU/ml on two consecutive tests of 3-month interval currently receiving TDF+ETV for more than 12 months Exclusion Criteria: - Cr ≥1.5 mg/dL Evidence of decompensated liver disease Malignant neoplasm Coinfection with HIV, HCV Proportion of Patients With a Sustained Virological Response (Serum HBV DNA Proportion of Patients With a Sustained Virological Response (Serum HBV DNA < Proportion of Patients With a Sustained Virological Response (Serum HBV DNA <20 IU/mL) at Week 48 Hepatitis B Hepatitis B, Chronic null --- M204V --- --- M204V ---

The purpose of this study is to evaluate the effectiveness of entecavir plus adefovir combination therapy versus entecavir monotherapy or therapy with adefovir plus lamivudine

NCT00410202

Conditions

1. Hepatitis B, Chronic

Interventions

1. Drug: Entecavir
2. Drug: Tenofovir
3. Drug: Adefovir
4. Drug: Lamivudine

MeSH:Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis

HPO:Hepatitis

Inclusion Criteria: - Evidence of lamivudine (LVD) resistance - Subjects must have a history of previous LVD treatment at screening, and must have evidence of at least 1 LVD resistance substitution (valine, isoleucine, or serine) at reverse transcriptase codon 204 (M204V/I/S) - Nucleoside- and nucleotide-naive, except for LVD, and had chronic hepatitis B (HBV) infection - Compensated liver function and must have met ALL of the following criteria:International normalization ratio (INR) ≤ 1.5; Serum albumin ≥ 3 g/dL (≥ 30 g/L); Serum total bilirubin ≤ 2.5 mg/dL (≤ 42.75 μmol/L) - HBV DNA > 1.72 x 10*4* IU/mL (approximately 10*5* copies/mL) - Documentation of hepatitis B e antigen (HBeAg) positive and hepatitis B e antibody (HBeAb) negative status at screening - alanine aminotransferase (ALT) ≤ 10 * upper limit of normal (ULN) at screening - Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study (and for up to 6 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized - WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. --- M204V ---

Post menopausal is defined as: - Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential - WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 72 hours prior to the start of investigational product Exclusion Criteria: - Evidence of decompensated cirrhosis - Coinfection with human immunodeficiency virus, hepatitis C virus , or hepatitis D virus - Women who are pregnant or breastfeeding - Sexually active fertile men not using effective birth control if their partners were WOCBP - Laboratory values out of protocol-specified range Inclusion Criteria: - Evidence of lamivudine (LVD) resistance - Subjects must have a history of previous LVD treatment at screening, and must have evidence of at least 1 LVD resistance substitution (valine, isoleucine, or serine) at reverse transcriptase codon 204 (M204V/I/S) - Nucleoside- and nucleotide-naive, except for LVD, and had chronic hepatitis B (HBV) infection - Compensated liver function and must have met ALL of the following criteria:International normalization ratio (INR) ≤ 1.5; Serum albumin ≥ 3 g/dL (≥ 30 g/L); Serum total bilirubin ≤ 2.5 mg/dL (≤ 42.75 μmol/L) - HBV DNA > 1.72 x 10*4* IU/mL (approximately 10*5* copies/mL) - Documentation of hepatitis B e antigen (HBeAg) positive and hepatitis B e antibody (HBeAb) negative status at screening - alanine aminotransferase (ALT) ≤ 10 * upper limit of normal (ULN) at screening - Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study (and for up to 6 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized - WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. --- M204V ---

With the availability of potent nucloes(t)ide analogues (NA), such as tenofovir disoproxil fumarate (TDF) and entecavir (ETV), suppression of serum HBV DNA to undetectable levels by polymerase chain reaction (PCR) assays became achievable in most NA treatment-naïve patients. Until recently, however, many patients commenced antiviral treatment with inferior NAs prior to the availability of TDF or ETV, such as lamivudine (LAM) which has a low genetic barrier to resistance. ETV resistance increase up to 51% of patients after 5 years of ETV treatment in lamivudine-refractory patients. Resistance to ETV appears to occur through a two-hit mechanism with initial selection of M204V/I mutation followed by amino acid substitutions at rtT184, rtS202, or rtM250. In vitro studies showed that ETV-resistant mutations are susceptible to TDF, but there are little clinical data on the efficacy of TDF monotherapy in patients with ETV-resistance. On the other hand, there was a retrospective cohort study reporting that, with the combination of TDF and ETV, most of patients became HBV DNA undetectable after median 6 months of treatment. Probability of reaching complete HBV DNA suppression was not decreased in patients with ADV or ETV-resistance. Thus, there is no consistent treatment recommendation for patients with ETV-resistance. In this clinical trial, the investigators will clarify whether tenofovir monotherapy is as effective as tenofovir plus entecavir in inducing complete virologic response in CHB patients with genotypic resistance to ETV and partial virologic response to ongoing treatment.

NCT01639092

Conditions

1. Chronic Viral Hepatitis B Without Delta-agent

Interventions

1. Drug: Tenofovir
2. Drug: Tenofovir
3. Drug: Entecavir

MeSH:Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis

HPO:Hepatitis

Resistance to ETV appears to occur through a two-hit mechanism with initial selection of M204V/I mutation followed by amino acid substitutions at rtT184, rtS202, or rtM250. --- M204V ---

This is a randomized, open-labelled, prospective 96-week study comparing the antiviral efficacy and safety of switching to entecavir 1 mg QD from lamivudine versus maintaining lamivudine 100 mg QD treatment in HBV-infected subjects currently receiving lamivudine monotherapy.

NCT00625560

Conditions

1. Hepatitis B, Chronic

Interventions

1. Drug: Entecavir
2. Drug: Lamivudine

MeSH:Hepatitis A Hepatitis B Hepatitis B, Chronic Hepatitis

HPO:Hepatitis

Exclusion Criteria: - All subjects will be tested for presence of M204V/I mutations in the YMDD motif at baseline. --- M204V ---

Subjects with M204V/I mutations in the YMDD motif at baseline are not eligible for the study. --- M204V ---