The role of measurement of hepatitis B "s" antigen (HBsAg) during the therapy with oral nucleos(t)ide analogues is still debatable. The HBsAg declines after 3 years of therapy with entecavir (ETV) was investigated among patients affected by hepatitis B virus (HBV), e antigen (HBeAg)-negative and genotypes A, D and E. A prospective cohort of 123 patients was enrolled consecutively from April 2007 to May 2010 with at least 3 years of treatment with ETV. Patients with chronic HBV infection, HBeAg-negative, naive for previous treatment and with virological response to ETV were included in the study. HBsAg level and HBV-DNA were tested every 3 months during the first year of treatment, then every 6 months for a time of at least 3 years. After 3 years, HBsAg decline was 0.77 log IU/ml, 0.65 log IU/ml, 0.45 respectively; A versus D (P = 0.012), A versus E (P < 0.001), D versus E (P < 0.001). In the multivariate linear regression analysis only the HBV genotype was predictive of HBsAg decline after 3 years of treatment (P < 0.001). The expected time to HBsAg loss was 15.6 years for the A genotype, 17 years for D, 24.6 years for E (P < 0.001). The treatment with ETV leads the different kinetics in HBsAg decline among genotypes A, D and E; the expected time of HBsAg loss was significantly higher in E genotype compared to A and D genotype.

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