title: Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B.
abstract: BACKGROUND
  Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B.
  
  
  METHODS
  In this phase 3, double-blind trial, we randomly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necroinflammatory score, without worsening of fibrosis).
  
  
  RESULTS
  Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated (70 percent), as compared with 174 of 287 such patients in the lamivudine group (61 percent, P=0.01). More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus (HBV) DNA levels according to a polymerase-chain-reaction assay (90 percent vs. 72 percent, P<0.001) and normalization of alanine aminotransferase levels (78 percent vs. 71 percent, P=0.045). The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with entecavir than with lamivudine (5.0 vs. 4.5 log [on a base-10 scale] copies per milliliter, P<0.001). There was no evidence of resistance to entecavir. Safety and adverse-event profiles were similar in the two groups.
  
  
  CONCLUSIONS
  Among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue, the rates of histologic improvement, virologic response, and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine. The safety profile of the two agents was similar, and there was no evidence of viral resistance to entecavir. (ClinicalTrials.gov number, NCT00035789.).
authors.affiliation: Queen Mary Hospital, Hong Kong, China. hrmelcl@hkucc.hku.hk
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.forename: Daniel
authors.initials: D
authors.lastname: Shouval
authors.forename: Anna S
authors.initials: AS
authors.lastname: Lok
authors.forename: Ting-Tsung
authors.initials: TT
authors.lastname: Chang
authors.forename: Hugo
authors.initials: H
authors.lastname: Cheinquer
authors.forename: Zachary
authors.initials: Z
authors.lastname: Goodman
authors.forename: Deborah
authors.initials: D
authors.lastname: DeHertogh
authors.forename: Richard
authors.initials: R
authors.lastname: Wilber
authors.forename: Richard C
authors.initials: RC
authors.lastname: Zink
authors.forename: Anne
authors.initials: A
authors.lastname: Cross
authors.forename: Richard
authors.initials: R
authors.lastname: Colonno
authors.forename: Lori
authors.initials: L
authors.lastname: Fernandes
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D005260:Female; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019259:Lamivudine; C413685:entecavir; D006147:Guanine