Background: Conventional interferon and lamivudine monotherapy are unsatisfac tory in treating hepatitis B virus (HBV) infection. Objective: To evaluate the e fficacy and safety of pegylated interferon- α 2b and lamivudine combination t herapy for chronic hepatitis B. Design: Randomized ,controlled, open- label tri al. Setting: Outpatient clinic in a referral center. Participants: 100 treatment - naive patients with hepatitis B e antigen (HBeAg)- positive chronic hepatiti s B and moderately elevated alanine aminotransferase levels. Measurement: The pr imary end point was sustained virologic response (HBeAg seroconversion and HBV D NA level < 500 000 copies/ml) at 24 weeks after cessation of treatment. Interven tion: A staggered regimen of combination therapy with pegylated interferon- α 2b (1.5 μ g/kg of body weight per week; maximum,100 μ g) given for 32 weeks p lus lamivudine (100 mg daily) given for 52 weeks versus lamivudine (100 mg daily ) monotherapy given for 52 weeks. Of the 100 participants,96% completed treatm ent and 80% completed post- treatment follow- up. Results: The rate of susta ined virologic response was 36% for the combination treatment group and 14% for the lamivudine monotherapy group (absolute difference, 22 percentage points [95% CI, 6 to 38 percentage points]). End- of- treatment outcomes showed tha t, compared with monotherapy, patients receiving combination therapy more often had virologic response (60% vs. 28% [absolute difference, 32 percentage poin ts (CI, 14 to 50 percentage points)]); had more substantial reductions of HBV DN A (3.91 log 10 copies/ml vs. 2.83 log10 copies/ml); and less often had lamivudin e resistant mutants (21% vs. 40% ). The percentages of patients with normaliz ation of alanine aminotransferase levels and histologic improvement did not diff er. Adverse effects, such as transient influenza- like symptoms, alopecia, and local erythematous reactions, were more common with combination therapy. Limitat ions: This study lacked a double- blind design and was conducted at 1 instituti on. Because of the staggered pegylated interferon- lamivudine regimen, patients assigned to combination therapy received treatment for 8 weeks longer than thos e assigned to monotherapy. Conclusions: In patients with HBeAg- positive chroni c hepatitis B, staggered combination treatment with pegylated interferon- α 2b and lamivudine may lead to a higher rate of virologic response than lamivudine monotherapy. Background: Conventional interferon and lamivudine monotherapy are unsatisfied in treating hepatitis B virus (HBV) infection. Objective: To evaluate the e fficacy and safety of pegylated interferon- α 2b and lamivudine combination therapy for chronic hepatitis B. Design: Randomized, controlled , open- label tri al. Setting: Outpatient clinic in a referral center. Participants: 100 treatment - naive patients with hepatitis B e antigen (HBeAg) - positive chronic hepatiti s B and moderately elevated alanine aminotransferase levels. point was sustained virologic response (HBeAg seroconversion and HBV D NA level <500 000 copies / ml) at 24 weeks after cessation of treatment. Interven tion: A staggered regimen of combination therapy with pegylated interferon- α 2b (1.5 μg / kg of body weight per week; maximum, 100 μg) given for 32 weeks p lus lamivudine (100 mg daily) given for 52 weeks versus lamivudine (100 mg daily) monotherapy given for 52 weeks. Of th e 100 participants, 96% completed treatm ent and 80% completed post-treatment follow-up. Results: The rate of susta ined virologic response was 36% for the combination treatment group and 14% for the lamivudine monotherapy group (absolute difference, 22 percentage points [95% CI, 6 to 38 percentage points]). End-of-treatment outcomes showed tha t, compared with monotherapy, patients receiving combination therapy more often had virologic response (60% vs. 28% [absolute difference, 32 had more substantial reductions of HBV DN A (3.91 log 10 copies / ml vs. 2.83 log10 copies / ml); and less often had lamivudin e resistant mutants (21% vs. 40%). The percentages of patients with normaliztion of alanine aminotransferase levels and histologic improvement did not diff er. Adverse effects, such as transient influenza-like symptoms, alopecia, and local erythematous reactions, were more common with combination therapy. Limitat ions: This s tudylacked a double-blind design and was conducted at 1 instituti on. Because of the staggered pegylated interferon-lamivudine regimen, patients assigned to combination therapy received treatment for 8 weeks longer than thos e assigned to monotherapy. Conclusions: In patients with HBeAg-positive chroni c hepatitis B, staggered combination treatment with pegylated interferon- α 2b and lamivudine may lead to a higher rate of virologic response than lamivudine monotherapy.