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Previous Volume 354:1011-1020 March 9, 2006 Number 10 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Hoofnagle, J. H. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear Related Article

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 [ClinicalTrials.gov] .)

Source Information

From the Queen Mary Hospital, Hong Kong, China (C.-L.L.); Hadassah-Hebrew University Hospital, Jerusalem, Israel (D.S.); University of Michigan, Ann Arbor (A.S.L.); National Cheng Kung University Medical College, Tainan, Taiwan (T.-T.C.); Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil (H.C.); Armed Forces Institute of Pathology, Washington, D.C. (Z.G.); University of Connecticut, Farmington (D.D.); and Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Conn. (R.W., R.C.Z., A.C., R.C., L.F.).

Address reprint requests to Dr. Lai at the University Department of Medicine, Queen Mary Hospital, Hong Kong, China, or at hrmelcl{at}hkucc.hku.hk.

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