title: IFN-alpha receptor mRNA expression in a United States sample with predominantly genotype 1a/I chronic hepatitis C liver biopsies correlates with response to IFN therapy.
abstract: Our aim was to assess whether, in the United States, with the predominant hepatitis C viral (HCV) genotypes 1a/I and 1b/II, hepatic interferon-alpha receptor (IFNAR) mRNA expression correlated with response to IFN therapy, levels of HCV RNA, or histologic activity index (HAI). Nine of 24 patients (38%) had an initial response to IFN treatment, 5 of whom (21%) had a sustained response. The corrected hepatic IFNAR mRNA expression (measured by RT-PCR) for the sustained responder group (mean +/- SE, 0.16 +/- 0.06, n = 5) was significantly higher than for the nonresponding group (0.059 +/- 0.01, n = 15) (p < 0.02). Patients who relapsed had an intermediate value (0.092 +/- 0.029, n = 4). Higher IFNAR expression was inversely correlated with a lower serum HCV RNA titer (p < 0.01), and responders to IFN treatment tended to have a lower titer of HCV RNA (p = 0.056). We found no significant correlation between the amounts of IFNAR with (1) the total HAI (low HAI < or = 7, IFNAR 0.076 +/- 0.013, n = 10; high HAI > or = 8, IFNAR 0.092 +/- 0.027, n = 14, ns) or (2) individual inflammation, necrosis, or fibrosis components of the HAI. As with Japanese HCV patients with genotypes 1b/II-2b/IV, higher hepatic IFNAR mRNA expression in the United States with predominant genotypes 1a/I and 1b/II appears to correlate with response to IFN therapy and a low HCV RNA titer but not with the total HAI or its components.
authors.affiliation: Department of Medicine and Biochemistry and Molecular Biology, University of Massachusetts Medical Center, Worcester 01655, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mathai
authors.forename: K
authors.initials: K
authors.lastname: Shimoda
authors.forename: B F
authors.initials: BF
authors.lastname: Banner
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: H L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: G F
authors.initials: GF
authors.lastname: Barnard
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001706:Biopsy; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000473:pathology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics*; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D014481:United States
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta