Entecavir vs lamivudine for HBeAg positive and negative chronic hepatitis B

Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, DeHertogh D, Wilber R, Zink RC, Cross A, Colonno R, Fernandes L; BEHoLD AI463027 Study Group. 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%), as compared with 174 of 287 such patients in the lamivudine group (61%, 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% vs. 72%, P < 0.001) and normalization of alanine aminotransferase levels (78% vs. 71%, 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.). [Abstract reproduced by permission of N Engl J Med 2006;354:1011-1020]. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J, Cross A, DeHertogh D, Wilber R, Colonno R, Apelian D; BEHoLD AI463022 Study Group. BACKGROUND: Entecavir is a potent and selective guanosine analogue with significant activity against hepatitis B virus (HBV). METHODS: In this phase 3, double-blind trial, we randomly assigned 715 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B who had not previously received a nucleoside analogue to receive either 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) at week 48. Secondary end points included a reduction in the serum HBV DNA level, HBeAg loss and seroconversion, and normalization of the alanine aminotransferase level. RESULTS: Histologic improvement after 48 weeks occurred in 226 of 314 patients in the entecavir group (72%) and 195 of 314 patients in the lamivudine group (62%, P = 0.009). More patients in the entecavir group than in the lamivudine group had undetectable serum HBV DNA levels according to a polymerase-chain-reaction assay (67% vs. 36%, P < 0.001) and normalization of alanine aminotransferase levels (68% vs. 60%, P = 0.02). The mean reduction in serum HBV DNA from baseline to week 48 was greater with entecavir than with lamivudine (6.9 vs. 5.4 log [on a base-10 scale] copies per milliliter, P < 0.001). HBeAg seroconversion occurred in 21% of entecavir-treated patients and 18% of those treated with lamivudine (P = 0.33). No viral resistance to entecavir was detected. Safety was similar in the two groups. CONCLUSIONS: Among patients with HBeAg-positive chronic hepatitis B, the rates of histologic, virologic, and biochemical improvement are significantly higher with entecavir than with lamivudine. The safety profile of the two agents is similar, and there is no evidence of viral resistance to entecavir. (ClinicalTrials.gov number, NCT00035633.). [Abstract reproduced by permission of N Engl J Med 2006;354:1001-1010].