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Impact of lamivudine-resistance mutations on entecavir treatment outcome in hepatitis B

Koffi, Josepha; Egounlety, Romancec; Pradat, Pierrea,c,d; Lebosse, Fannya; Si-Ahmed, Si-Nafaa; Lussier, Véroniquea; Chevallier, Philippeb; Bailly, Françoisa,c,d; Zoulim, Fabiena,c,d,e

European Journal of Gastroenterology & Hepatology: February 2014 - Volume 26 - Issue 2 - p 146–154
doi: 10.1097/MEG.0b013e328365c3e5
Original Articles: Hepatitis

Background and objective Entecavir (ETV) is a potent inhibitor of viral replication in nucleos(t)ide analog (NA)-naive chronic hepatitis B patients with a very low rate of resistance (≤1.2%) over 5 years. The aim of this study was to assess the efficacy of ETV treatment in routine clinical practice and to investigate whether persistence of residual viral replication was the result of the emergence and selection of drug-resistant mutants.

Patients and methods Chronic hepatitis B patients treated with ETV were consecutively recruited from the Department of Hepatology, Hospices Civils de Lyon, France, and were monitored regularly within their routine clinical follow-up. Virological, biochemical, clinical, and tolerance findings were assessed prospectively.

Results A total of 79 patients were studied, of whom 58% received ETV as a first-line therapy. During ETV therapy (median follow-up 42 months), hepatitis B virus (HBV) DNA became undetectable in 95% of patients. Time to HBV DNA undetectability was significantly shorter in patients with an HBV DNA level less than 4 log10 IU/ml at baseline and in HBeAg-negative patients. Moreover, time to undetectability was significantly shorter in patients with no or only one lamivudine-resistance (LAMr) mutation than in patients with two or more LAMr mutations (P=0.050). No patient had renal-function impairment during ETV therapy.

Conclusion In routine clinical practice, ETV is effective in both NA-naive and NA-experienced patients, except in patients with HBV strains harboring at least two LAMr mutations. The analysis of viral genome sequence at the time of treatment adaptation could prove useful to personalize antiviral therapy in patients failing a previous line of treatment.

Departments of aHepatology

bVirology, Croix-Rousse Hospital, Hospices Civils de Lyon


dLyon 1 University

eInstitut Universitaire de France, Paris, France

Correspondence to Fabien Zoulim, MD, PhD, INSERM U1052, 151 Cours Albert Thomas, 69003 Lyon, France Tel: +33 4 72 68 19 70; fax: +33 4 72 68 19 71; e-mail:

Received July 12, 2013

Accepted August 12, 2013

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins