Complexity and diversity of hepatitis B virus quasispecies: Correlation with long-term entecavir antiviral efficacy

• Longitudinal evolution of HBV quasispecies after entecavir therapy was determined.
• A large number of sequences were analyzed.
• HBV quasispecies complexity was reduced in responders after entecavir therapy.
• HBV quasispecies diversity was reduced in responders after entecavir treatment.

This study was undertaken to determine the complexity and diversity of hepatitis B virus (HBV) quasispecies during long-term antiviral therapy and examine their impacts on therapeutic outcome. Six chronic hepatitis B patients receiving entecavir monotherapy (0.5 mg/day) for 3 years were enrolled. The reverse transcriptase region of the HBV polymerase gene was sequenced and HBV quasispecies complexity and diversity were calculated. Sustained virological response (SVR) was defined as serum HBV DNA <57 IU/ml from 48 weeks after treatment to the end of follow up. Four patients achieved a SVR and the other two had a virological breakthrough at week 24. Despite comparable baseline levels, the complexity and diversity of HBV quasispecies were significantly (p < 0.05) reduced in sustained responders versus the patients with a virological breakthrough 48 weeks after treatment. Thus, reduction in HBV quasispecies complexity and diversity may predict an SVR to long-term entecavir monotherapy.