Changes of HBsAg and HBV DNA levels in Chinese chronic hepatitis B patients after 5 years of entecavir treatment

Background and AimHepatitis B surface antigen (HBsAg) kinetics during long-term entecavir therapy has not been well investigated. MethodsWe described the cumulative serologic, virologic, and biochemical outcomes and the occurrence of signature entecavir mutations among 222 Chinese treatment-naive chronic hepatitis B (CHB) patients receiving entecavir for up to 5 years. ResultsThe median rate of HBsAg reduction over 5 years was 0.125 log IU/mL/year. Patients with high baseline HBV DNA levels (8 log copies/mL or 7.3 log IU/mL), when compared with those with baseline hepatitis B virus (HBV) DNA <7.3 log IU/mL, had a significantly greater median rate of HBsAg reduction (0.178 and 0.102 log IU/mL/year, respectively, P<0.001). The difference in HBsAg decline was most prominent in the first year (0.324 and 0.062 log IU/mL/year, respectively, P<0.001). Greater median rates of HBsAg reduction were also found in hepatitis B e antigen (HBeAg)-positive patients when compared with HBeAg-negative patients (0.144 and 0.098 log IU/mL/year, P=0.015), and in patients with high baseline HBsAg levels (3 log IU/mL), when compared with patients with low baseline HBsAg <3 log IU/mL (0.131 and 0.045 log IU/mL/year, respectively, P=0.001). The 5-year cumulative rate of HBV DNA undetectability (<20 IU/mL) was 97.1%. There were two cases of entecavir resistance, resulting in a 5-year cumulative resistance rate of 1.2%. ConclusionIn contrast to the profound HBV DNA suppression, long-term entecavir treatment achieved only a slow decline in serum HBsAg. Although certain patient subgroups exhibit a more rapid HBsAg reduction, additional therapeutic agents are needed to increase the chance of HBsAg seroclearance in CHB.