Co-infection by serologically-silent hepatitis B virus may contribute to poor interferon response in patients with chronic hepatitis C by down-regulation of type-I interferon receptor gene expression in the liver

Intrahepatic mRNA levels of type-I interferon (IFN) receptor genes have bee n shown to correlate with the clinical efficacy of IFN therapy in patients with chronic hepatitis C. Recently, co-infection by serologically-silent he patitis B virus (HBV) has been assumed to be associated with the poor IFN r esponse in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between the coinfection of serologically-silen t HBV and type-I IFN receptor gene expression in the liver of patients with chronic hepatitis C. The intrahepatic mRNA levels of IFNAR2, one of the tw o subunits of the type-I IFN receptor, were quantified and compared with bo th the prevalence of HBV DNA and the hepatitis C virus (HCV) genotype in 45 patients with chronic hepatitis C, who were negative for hepatitis B surfa ce antigen. Go-infection, as evaluated by a nested polymerase chain reactio n, was present in 22 patients (48.9%), with dominance of the HCV genotype 1 b (65.2%) over genotype 2a (31.8%). Go-infection was associated with lower IFNAR2 mRNA levels, higher levels of serum HCV RNA, and a poor IFN response , regardless of the HCV genotype. The findings suggest the possibility that co-infection by serologically-silent HBV is one of the factors that can le ad to an unfavorable IFN response in chronic hepatitis C by downregulation of IFN receptor gene expression in the liver. J. Med. Virol. 63:220-227, 20 01. (C) 2001 Wiley-Liss, Inc.