We conducted this trial at 16 outpatient gastroenterology clinics at academic centers in Hong Kong, Australia, Canada, France, Korea, Singapore, Taiwan, Thailand, and the United States. Study investigators recruited participants from among their clinic patients after reviewing medical records and completing screening procedures to assess eligibility. Eligible patients were men or women with chronic hepatitis B 18 to 70 years of age, with no history or signs of hepatic decompensation, positivity for serum hepatitis B surface antigen (HBsAg), positivity for serum HBeAg, serum alanine aminotransferase (ALT) level between 1.3 and 10 times the upper limit of normal, and serum HBV DNA levels of at least 6 log10 copies/mL. We excluded patients who were pregnant, breastfeeding, or co-infected with hepatitis C or D virus or HIV; had other known causes of liver disease, a history or signs of pancreatitis or hepatocellular carcinoma, or potentially confounding concomitant medical conditions; had ever been treated for hepatitis B with nucleoside or nucleotide analogues or had received interferon or other immunomodulatory agents within 12 months of screening; or had used alcohol or illicit drugs in the past 2 years. Patients with elevated serum creatinine levels, hemoglobin levels less than 110 g/L for men or less than 100 g/L for women, an absolute neutrophil count less than 2 × 109 cells/L, platelet counts less than 100 × 109 cells/L, α-fetoprotein levels greater than 50 µg/L, serum amylase or lipase levels at least 1.5 times the upper limit of normal, a prothrombin time prolonged by more than 3 seconds above the upper limit of normal, albumin levels less than 34 g/L, or total bilirubin levels at least 2 times the upper limit of normal were also excluded.