title: 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.
abstract: Intrahepatic mRNA levels of type-I interferon (IFN) receptor genes have been shown to correlate with the clinical efficacy of IFN therapy in patients with chronic hepatitis C. Recently, co-infection by serologically-silent hepatitis B virus (HBV) has been assumed to be associated with the poor IFN response in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between the co-infection of serologically-silent 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 two subunits of the type-I IFN receptor, were quantified and compared with both 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 surface antigen. Co-infection, as evaluated by a nested polymerase chain reaction, was present in 22 patients (48.9%), with dominance of the HCV genotype 1b (65.2%) over genotype 2a (31.8%). Co-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 lead to an unfavorable IFN response in chronic hepatitis C by down-regulation of IFN receptor gene expression in the liver.
authors.affiliation: 2nd Department of Internal Medicine, Shimane Medical University, Izumo-Shi, Shimane, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Fukuda
authors.forename: N
authors.initials: N
authors.lastname: Ishimura
authors.forename: S
authors.initials: S
authors.lastname: Hamamoto
authors.forename: M
authors.initials: M
authors.lastname: Moritani
authors.forename: Y
authors.initials: Y
authors.lastname: Uchida
authors.forename: S
authors.initials: S
authors.lastname: Ishihara
authors.forename: S
authors.initials: S
authors.lastname: Akagi
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000097:blood; D015536:Down-Regulation; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006509:Hepatitis B / Q000150:complications* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000096:biosynthesis / Q000235:genetics*; D011994:Recombinant Proteins
chemical_list: D004279:DNA, Viral; C508033:IFNAR2 protein, human; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008565:Membrane Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta