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This study was undertaken to compare the early antiviral activity and viral kinetic profiles of entecavir (ETV) versus adefovir (ADV) in hepatitis B e antigen positive nucleoside-naïve adults with chronic hepatitis B (CHB). Sixty-nine nucleoside-naïve CHB patients with baseline HBV DNA of 10 8 copies/mL or more were randomized 1:1 to open-label treatment with entecavir 0.5 mg/day or adefovir 10 mg/day for a minimum of 52 weeks. The primary efficacy analysis compared mean reduction in HBV DNA at week 12 adjusted for baseline levels using linear regression. Entecavir was superior to adefovir for mean change from baseline in HBV DNA at week 12 (؊6.23 log 10 copies/mL versus ؊4.42 log 10 copies/mL, respectively; mean difference ؊1.58 log 10 copies/mL; P < 0.0001). Both drugs demonstrated biphasic viral kinetics, with a first phase of rapid decline lasting 10 days. A significant difference favoring ETV was reached at day 10 (day 10 ETV؊ADV difference estimate: ؊0.66 log 10 copies/mL; 95% CI [؊0.30, ؊0.01]). Early virological response was found to be predictive of subsequent virological response, with those having lower HBV DNA levels at day 10 being more likely to achieve HBV DNA of less than 300 copies/mL at week 48. In addition, there was considerably less variability in the extent of HBV DNA reductions in patients treated with entecavir versus adefovir. Both the mean decrease in serum HBV DNA and the proportion of patients achieving HBV DNA less than 300 copies/mL were greater in entecavir-treated than adefovir-treated patients at weeks 2, 4, 8, 12, 24, and 48. At week 48, one (3%) ETV-treated versus 15 (47%) ADV-treated patients had HBV DNA of 10 5 copies/mL or more. Both antivirals were well tolerated. Conclusion: Entecavir therapy resulted in earlier and superior reduction in HBV DNA compared with adefovir in nucleoside-naïve HBeAg-positive patients with CHB. (HEPATOLOGY 2009;49:72-79.)

Hepatitis B virus (HBV) infection is common with major clinical consequences worldwide. In Asian Americans, the HBsAg carrier rate ranges from 7 to 16%; HBV is the most important cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Patients are first diagnosed at different stages of clinical disease, which is categorized by biochemical and virologic tests. Patients at risk for liver complications should be identified and offered antiviral therapy. The two antiviral agents recommended for first-line treatment of chronic hepatitis B (CHB) are entecavir and tenofovir. The primary goal of therapy is sustained suppression of viral replication to achieve clinical remission, reverse fibrosis, and prevent and reduce progression to end-stage liver disease and HCC. Asian patients with chronic hepatitis, either HBeAg-positive or -negative, with HBV DNA levels >10(4) copies/mL (>2,000 IU/mL) and alanine aminotransferase (ALT) values above normal are candidates for antiviral therapy. HBeAg-negative patients with HBV DNA >10(4) copies/mL (>2,000 IU/mL) and normal ALT levels but who have either serum albumin ≤3.5 g/dL or platelet count ≤130,000 mm(3), basal core promoter mutations, or who have first-degree relatives with HCC should be offered treatment. Patients with cirrhosis and detectable HBV DNA must receive antiviral therapy. Considerations for treatment include pregnant women with high viremia, coinfected patients, and those requiring immunosuppressive therapy. In HBsAg-positive patients with risk factors, lifelong surveillance for HCC with alpha-fetoprotein testing and abdominal ultrasound examination at 6-month intervals is required. These recommendations are based on a review of relevant literature and the opinion of a panel of Asian American physicians with expertise in hepatitis B treatment.