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Entecavir vs. Lamivudine for Chronic HBV Infection

In a 1-year study, entecavir was superior to lamivudine in the treatment of both HBeAg-positive and HBeAg-negative chronic HBV infections.

Current treatment options for hepatitis B virus (HBV) infection include interferon, lamivudine, adefovir, and entecavir. This last agent is a recently approved nucleoside analogue that is a highly selective inhibitor of HBV DNA polymerase. Investigators compared the efficacy and safety of entecavir versus lamivudine in two studies of patients with chronic HBV infection.

Both studies were international, phase 3, double-blind, double-dummy, randomized controlled trials, sponsored by the maker of entecavir. One study focused on hepatitis B e-antigen (HBeAg)-positive patients, and the other on HBeAg-negative patients. In each study, patients received daily entecavir (0.5 mg) or lamivudine (100 mg) for 52 weeks. The primary endpoint was the proportion of patients with histologic improvement at 48 weeks (defined as at least a 2-point decrease in the Knodell necroinflammatory score, without worsening of fibrosis). Secondary endpoints included 48-week virologic response (HBV DNA levels <300 copies/mL by PCR assay) and, in the study of HBeAg-positive patients, HBeAg loss and seroconversion.

In the HBeAg-positive study, researchers screened 1056 patients and randomized 715. Of these, 628 had adequate liver biopsies at baseline. More than 90% of patients in each treatment group completed 52 weeks of therapy. Adequate liver biopsies were obtained at 48 weeks in 93% of entecavir patients and in 86% of lamivudine patients. The entecavir group had a significantly higher rate of both histologic improvement (72% vs. 62%; P=0.009) and virologic response (67% vs. 36%; P<0.001) than did the lamivudine group. The two groups had similar rates of HBeAg loss (22% and 20%) and HBeAg seroconversion (21% and 18%). Drug resistance did not occur in the entecavir group; however, 14% of patients in the lamivudine group developed the YMDD mutation. Frequency of adverse events was similar in both groups.

In the HBeAg-negative study, researchers screened 1468 patients and randomized 648. Of these, 583 had adequate liver biopsies at baseline. More than 95% of patients in each treatment group completed 52 weeks of therapy. Adequate liver biopsies were obtained at 48 weeks in 90% of entecavir patients and in 87% of lamivudine patients. Again, the entecavir group had significantly higher rates of histologic improvement (70% vs. 61%; P=0.01) and virologic response (90% vs. 72%, P<0.001) than did the lamivudine group. The entecavir group had no occurrences of drug resistance, whereas 7% of patients in the lamivudine group developed the YMDD mutation. Frequency of adverse events was similar in both groups.

Comment: The results from these large, well-designed, phase 3 trials demonstrate the superiority of entecavir over lamivudine in the treatment of both HBeAg-positive and HBeAg-negative chronic HBV infections. Entecavir was superior in terms of both histologic improvement and virologic response at 48 weeks. Ten patients would need to be treated with this agent for one to achieve histologic improvement. In addition, entecavir did not lead to any drug resistance during the first year of therapy. Long-term follow-up is necessary to determine whether drug resistance eventually develops in entecavir-treated patients and whether higher rates of seroconversion are seen with long-term therapy in HBeAg-positive patients.

— Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology July 10, 2006

Citation(s):

Chang T-T et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006 Mar 9; 354:1001-10.

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Lai C-L et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2006 Mar 9; 354:1011-20. [Erratum in: N Engl J Med 2006 Apr 27; 354:1863.]

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