Dataset Information

Efficacy of entecavir-tenofovir combination therapy for chronic hepatitis B patients with multidrug-resistant strains.

ABSTRACT: The emergence of multidrug-resistant (MDR) strains of hepatitis B virus (HBV) is a major concern. This study aimed to investigate the efficacy and safety of combination therapy with entecavir (ETV) plus tenofovir disoproxil fumarate (TDF) against MDR HBV. To adjust for differences in baseline characteristics, inverse probability weighting (IPW) using propensity scores for the entire cohort and weighted Cox proportional hazards models were applied. Ninety-three consecutive patients who were treated with ETV-TDF combination therapy for >6 months were included; at baseline, 45 were infected with HBV strains with genotypic resistance to lamivudine (LAM) and ETV (the LAM/ETV-R group), 28 with strains resistant to LAM and adefovir (ADV) (the LAM/ADV-R group), and 20 with strains resistant to LAM, ETV, and ADV (the LAM/ETV/ADV-R group). The median duration of rescue therapy was 13.0 (range, 6.7 to 31.7) months. Seventy-four of 93 patients (79.6%) achieved complete virologic suppression, after a median of 4.5 (95% confidence interval, 3.0 to 6.0) months. The cumulative probability of complete virologic suppression at month 6 was 63.6% (55.7%, 75.0%, and 65.0% in the LAM/ETV-R, LAM/ADV-R, and LAM/ETV/ADV-R groups, respectively). During the treatment period, these probabilities were not significantly different across the resistance profiles before and after IPW (P = 0.072 and P = 0.510, respectively). In multivariate analysis, a lower baseline HBV DNA level, but not resistance profiles, was an independent predictor of complete virologic suppression. Renal dysfunction was not observed during the treatment period. In conclusion, rescue therapy with ETV-TDF combination is efficient and safe in patients infected with MDR HBV strains regardless of the antiviral drug resistance profiles.

SUBMITTER: Lee YB

PROVIDER: S-EPMC4249402 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Efficacy of entecavir-tenofovir combination therapy for chronic hepatitis B patients with multidrug-resistant strains.

Lee Yun Bin YB Lee Jeong-Hoon JH Lee Dong Hyeon DH Cho Hyeki H Ahn Hongkeun H Choi Won-Mook WM Cho Young Youn YY Lee Minjong M Yoo Jeong-Ju JJ Cho Yuri Y Cho Eun Ju EJ Yu Su Jong SJ Kim Yoon Jun YJ Yoon Jung-Hwan JH Kim Chung Yong CY Lee Hyo-Suk HS

Antimicrobial agents and chemotherapy 20140825 11

The emergence of multidrug-resistant (MDR) strains of hepatitis B virus (HBV) is a major concern. This study aimed to investigate the efficacy and safety of combination therapy with entecavir (ETV) plus tenofovir disoproxil fumarate (TDF) against MDR HBV. To adjust for differences in baseline characteristics, inverse probability weighting (IPW) using propensity scores for the entire cohort and weighted Cox proportional hazards models were applied. Ninety-three consecutive patients who were treat ...[more]

PMID: 25155601

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Project description:The objective of this study was to evaluate the effectiveness and safety of entecavir (ETV) and interferon (IFN) combination therapy in the treatment of chronic hepatitis B (CHB) mono-infection via a meta-analysis of randomized controlled trials (RCTs). All eligible RCTs evaluating combination therapy for treating CHB were identified from nine electronic databases. A meta-analysis was performed in accordance with the Cochrane Systemic Review handbook. Eleven trials encompassing 1010 participants were included in this meta-analysis. It showed that at 12 and ≥ 96 weeks of therapy, the combination of ETV and IFN was not better than ETV in improving the undetectable HBV DNA (12 weeks: RR=1.12, 95% CI=0.88-1.42; ≥ 96 weeks: RR = 0.64, 95% CI=0.21-1.98, respectively) and HBeAg seroconversion rates (12 weeks: RR=1.35, 95% CI=0.60-3.04; ≥ 96 weeks: RR=1.36, 95% CI=0.75-2.64, respectively). But at 48 weeks of therapy and approximately 2 years of follow up, combination therapy was superior to ETV in improving the undetectable HBV DNA (48 weeks: RR=1.46, 95% CI=1.13-1.90; follow up: RR=2.20, 95% CI=1.26-3.81, respectively) and HBeAg seroconversion rates (48 weeks: RR=1.82, 95% CI=1.44-2.30; follow up: RR=1.92, 95% CI=1.19-3.11, respectively). When compared to IFN group, at 24 and 48 weeks of therapy, combination group showed a greater undetectable HBV DNA (24 weeks: RR=2.14, 95% CI=1.59-2.89; 48 weeks: RR=2.28, 95% CI=1.54-3.37, respectively) and ALT normalization rate (24 weeks: RR=1.56, 95% CI= 1.24-1.96; 48 weeks: RR=1.55, 95% CI = 1.16-2.07, respectively). At 48 weeks of therapy, combination group achieved a greater HBeAg seroconversion rate than IFN (48 weeks: RR=1.58, 95% CI=1.24-2.00). No significant differences were observed in the side effects of the three therapies. So we can conclude that ETV and IFN combination therapy is more effective than ETV or IFN mono-therapy in CHB treatment. ETV, IFN, and the combination of the two are safe in CHB treatment.

Project description:BackgroundSome reports have documented the coexistence of Hepatitis B surfage Antigen (HBsAg) and anti-HBsAg antibodies (HBsAb) in patients with chronic hepatitis B (CHB), often in the absence of amino acid substitutions in the HBsAg sequences of the Hepatitis B Virus (HBV) genome able to explain an immunological escape variant.HBV genome has a very compact coding organization, with four partially overlapping open reading frames (ORFs). Because the reverse transcriptase region (rt) of HBV polymerase overlaps the HBsAg ORF, it is possible that some mutations in the HBsAg region correspond to mutations in the rt ORF, conferring resistance to current antiviral therapies. This unique case explores the response to antiviral therapies of a CHB with concurrent HBsAg and HBsAb positivity, and analyse the clinical implications of possible mutations in rt and HBsAg ORFs.Case presentationHere we describe the case of a 59 year-old Italian man suffering from Hepatitis B envelope Antigen (HBeAg) positive CHB with concurrent HBsAb positivity. By ultra-deep pyro-sequencing (UDPS) technique, mutations conferring immunological escape or resistance to antiviral therapies were found neither in HBsAg nor in HBV rt ORFs, respectively. The patient was unsuccessfully treated with interferon, adefovir monotherapy and adefovir plus entecavir combination. Surprisingly, during entecavir plus tenofovir combination, anti-HBe seroconversion and HBsAg loss were observed, while the titer of HBsAb persisted.ConclusionsConcurrent HBsAg/HBsAb positivity in active CHB is a clinical and virological dilemma. In this setting, there are not consistent data about the response to conventional therapies and the immunological balance between host and virus remains so far unexplained. This is, to our knowledge, the first case described of a CHB with HBsAg/HBsAb positivity, wild type for clinically relevant mutations in HBsAg and rt ORFs, successfully treated with a combination of nucleot(s)ide analogues (NAs).

Dataset Information

Efficacy of entecavir-tenofovir combination therapy for chronic hepatitis B patients with multidrug-resistant strains.

Publications

Efficacy of entecavir-tenofovir combination therapy for chronic hepatitis B patients with multidrug-resistant strains.

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