High efficacy of adefovir and entecavir combination therapy in patients with nucleoside-refractory hepatitis B

Chae, Hee Bok; Kim, Mee Jin; Seo, Eui Geun; Choi, Yong Hyeok; Lee, Jun Young; Han, Joung Ho; Yoon, Soon Man; Park, Seon Mee; Youn, Sei Jin

doi:10.3350/kjhep.2012.18.1.75

Cited by 12 publications

(11 citation statements)

References 18 publications

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“…Though LAM + ADV has been widely used for rescue therapy in past years for those patients [5,13], patients with sequential LAM and ADV resistance had resistant mutations on the same HBV genome, which anticipated that the combination therapy of LAM + ADV might be unsatisfactory for the CHB patients with genotypic resistance associated with sequential LAM and ADV treatment. Indeed, recent data also showed that the combination therapy of LAM + ADV was not effective and was inferior to ETV containing treatment in suppressing HBV DNA [14], which indicated that ETV based combination therapy would be more superior to the LAM + ADV combination therapy in management of LAM- or ADV- resistant patients.…”

Section: Discussionmentioning

confidence: 99%

Entecavir plus adefovir rescue therapy for chronic hepatitis B patients after multiple treatment failures in real-life practice

Yang

et al. 2013

Virol J

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AimTo evaluate the efficacy and safety of Entecavir (ETV) plus adefovir (ADV) for chronic hepatitis B (CHB) patients after multiple nucleos(t)ide analogue (NAs) failure treatment.MethodsHepatitis B e antigen (HBeAg)-positive patients who had a suboptimal response or developed resistance to two or more previous NAs treatments were included, and all subjects were treated with ETV in combination with ADV for ≥ 24 months. Complete virologic response (CVR) was defined as an undetectability of serum hepatitis B virus (HBV) DNA level during treatment. Safety assessment was based on the increasing of serum creatinine and creatine kinase levels.ResultsA total of 45 eligible patients were included. Twenty-five patients had been treated with lamivudine (LAM) or telbivudine (LdT) and developed genotypic resistance. Resistance to ADV was present in 18 patients and 4 patients had a suboptimal response to ETV. Two patients had a resistance to both LAM and ADV. The cumulative probabilities of CVR at 12 and 24 months of ETV + ADV treatment were 88.9% (40/45) and 97.8% (44/45), respectively. Although one patient failed to achieve CVR, its serum HBV DNA level decreased by 3.3 log copies/mL after 24 months of combination therapy. The cumulative probability of HBeAg seroconversion was 15.6% (7/45) and 26.7% (12/45) at 12 and 24 months of treatment, respectively. History of prior exposure to specific NAs did not make a difference to ETV + ADV treatment outcome. There were no significant adverse events related to ETV + ADV therapy observed in the study subjects.ConclusionETV + ADV can be used as an effective and safe rescue therapy in patients after multiple NA therapy failures, especially in the areas where tenofovir is not yet available.

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Section: Discussionmentioning

confidence: 99%

Entecavir plus adefovir rescue therapy for chronic hepatitis B patients after multiple treatment failures in real-life practice

Yang

et al. 2013

Virol J

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“…Moreover, modification of the treatment strategy may be required in the absence of EVR. Another ADV combination, such as ADV plus ETV, could be an alternative therapy [24,25,26], but the cost will be increased. In addition, the efficacy of ADV plus ETV needs to be demonstrated compared with that of the ADV plus LMV combination because a previous retrospective study failed to show its benefit [27].…”

Section: Discussionmentioning

confidence: 99%

Adefovir and Lamivudine Combination Therapy in Patients with Entecavir-Resistant Chronic Hepatitis B: Antiviral Responses and Evolution of Mutations

et al. 2014

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Objective: This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection. Methods: Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled. Results: Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log₁₀ IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log₁₀ IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%). Conclusions: ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients.

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“…The continued use of LAM does not provide any additional antiviral suppression but has been shown to delay the emergence of ADV resistance compared with switching to ADV alone . Nevertheless, resistance to both ADV and LAM can eventually develop during ADV + LAM treatment, and a substantial number of LAM‐experienced patients will have a suboptimal response to ADV + LAM . For TDF, evidence on its clinical efficacy in this patient population has been mainly provided from cohort and case–control studies, with the number of LAM‐resistant patients in TDF registrational trials too small to establish its efficacy in this subgroup, and results from one randomized controlled trial in LAM‐resistant HBV only recently being reported .…”

Section: Introductionmentioning

confidence: 99%

Entecavir plus adefovir versus adefovir plus lamivudine in hepatitis B virus e antigen‐positive, lamivudine‐resistant chronic hepatitis B

Heo

Ahn

Kweon

et al. 2014

J of Gastro and Hepatol

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Background and Aim: In areas of the world where tenofovir disoproxil fumarate is not marketed, adefovir (ADV) + lamivudine (LAM) is recommended and widely used for LAM-resistant chronic hepatitis B (CHB). This study hypothesizes that entecavir (ETV) + ADV, where both components are active against LAM-resistant hepatitis B virus (HBV), will provide greater antiviral potency than ADV + LAM where only ADV is active. Methods: Open-label, randomized trial in hepatitis B virus e antigen-positive LAMexperienced CHB patients with LAM resistance treated with ETV 1 mg + ADV 10 mg (n = 138), ADV + LAM 100 mg (n = 137), or ETV (n = 140). Results: At week 48, there was no significant difference in the primary endpoint of HBV-DNA < 50 IU/mL between the treatment groups (25.4% [ETV + ADV] vs 19.7% [ADV + LAM], P = 0.2619; vs 16.4% [ETV], P = 0.1336). However, at week 96, rates of HBV-DNA < 50 IU/mL were significantly greater with ETV + ADV than with ADV + LAM (43.5% vs 28.5%; P = 0.0095). Rates of virologic breakthrough and resistance to ETV or ADV were low through week 96 with both combinations. The delayed benefit of ETV + ADV is likely related to the high baseline viremia in this cohort relating to continued LAM exposure after treatment failure. All three therapies had favorable safety profiles. Conclusions:In patients with LAM-resistant HBV, ETV + ADV demonstrated greater antiviral efficacy than ADV + LAM and comparable safety over 2 years, and may therefore be a preferable treatment option for LAM-resistant CHB, especially in regions where alternative rescue therapies are not available. In highly viremic patients, the benefit of ETV + ADV became apparent after a longer treatment duration.

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High efficacy of adefovir and entecavir combination therapy in patients with nucleoside-refractory hepatitis B

Cited by 12 publications

References 18 publications

Entecavir plus adefovir rescue therapy for chronic hepatitis B patients after multiple treatment failures in real-life practice

Entecavir plus adefovir rescue therapy for chronic hepatitis B patients after multiple treatment failures in real-life practice

Adefovir and Lamivudine Combination Therapy in Patients with Entecavir-Resistant Chronic Hepatitis B: Antiviral Responses and Evolution of Mutations

Entecavir plus adefovir versus adefovir plus lamivudine in hepatitis B virus e antigen‐positive, lamivudine‐resistant chronic hepatitis B

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