title: Impact of lamivudine-resistance mutations on entecavir treatment outcome in hepatitis B.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of aHepatology bVirology, Croix-Rousse Hospital, Hospices Civils de Lyon cINSERM U1052 dLyon 1 University eInstitut Universitaire de France, Paris, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Koffi
authors.forename: Romance
authors.initials: R
authors.lastname: Egounlety
authors.forename: Pierre
authors.initials: P
authors.lastname: Pradat
authors.forename: Fanny
authors.initials: F
authors.lastname: Lebosse
authors.forename: Si-Nafa
authors.initials: SN
authors.lastname: Si-Ahmed
authors.forename: Véronique
authors.initials: V
authors.lastname: Lussier
authors.forename: Philippe
authors.initials: P
authors.lastname: Chevallier
authors.forename: François
authors.initials: F
authors.lastname: Bailly
authors.forename: Fabien
authors.initials: F
authors.lastname: Zoulim
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005602:France; D005838:Genotype; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019259:Lamivudine; C413685:entecavir; D006147:Guanine