Clinical features and viral quasispecies characteristics associated with infection by the hepatitis B virus G145R immune escape mutant

Coexistence of the hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) is an uncommon phenomenon, and the underlying mechanisms remain largely unknown. Amino-acid (aa) substitution from glycine to arginine at aa 145 (G145R), in the major hydrophilic region, has been reported in patients with HBsAg and anti-HBs coexistence. However, there is limited knowledge about the clinical features and viral quasispecies characteristics associated with G145R mutant hepatitis B virus (HBV) infection. We herein describe the dynamic changes in the serological and virological markers in a case of hepatitis B with coexisting HBsAg and anti-HBs, caused by a G145R immune escape mutant (genotype C). Entecavir was administered during the 4th week after admission. Alanine aminotransferase peaked in the 16th week, while both the HBsAg and HBeAg declined rapidly. HBsAg clearance and hepatitis B surface antigen (HBeAg)/hepatitis B surface antibody (anti-HBe) seroconversion were achieved in the 36th week, and then entecavir was withdrawn. A follow-up of 96 weeks showed that HBV DNA remained undetectable and that anti-HBs was maintained above 100 mIU/mL. The quasispecies characteristics of the G145R mutant HBV were investigated via ultra-deep sequencing. The complexity and genetic distance of the S and RT regions were much higher in the 8th week than at baseline or in the 4th week. Moreover, the frequencies of mutations (L173P, Q181R and A184V) in cytotoxic T lymphocyte epitopes increased before entecavir treatment. These findings extend understanding of the evolution of HBV under host immune pressure and of the clinical outcomes of affected patients.