The response to interferon is influenced by hepatitis B virus genotype in vitro and in vivo

Purpose: To investigate the effectiveness of an interferon administration on different genotypes of hepatitis B virus (HBV) in vitro and in vivo. Methods: In vitro, we transfected plasmids carrying different HBV genotypes including recently identified new genotype I into HepG2 and HuH7 cells, then treated with standard interferon alpha (IFN-alpha); in vivo, we treated mice with pegylated interferon alpha (Peg-IFN-alpha) after injection with HBV DNA of different genotypes. The culture supernatants from cell culture and sera from mice were collected and used in hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) assays by ELISA and HBV DNA measurement by PCR. Results: Both in cell culture and in mouse model, it was observed that HBV genotypes A and B exhibited significantly better response to IFN-alpha 2a or Peg-IFN-alpha 2a in terms of reduced expression of HBsAg, HBeAg and the HBV DNA level as compared to HBV genotypes C and D. Moreover, the inhibitory effect of IFN-alpha 2a or Peg-IFN-alpha 2a on HBV genotype I was greater than on genotype C or D, but less than genotype A. However, there was no significant response difference between genotypes A and B, C and D, B and I, respectively. Conclusion: The effectiveness of IFN/Peg-IFN to suppress HBV replication is dependent on different HBV genotypes. IFN/Peg-IFN is more effective on HBV genotype A or B than on genotype C, D or I. Treatment regimens are suggested to be adapted to HBV genotype. (C) 2012 Elsevier B.V. All rights reserved.