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

Our aim was to assess whether, in the United States, with the predominant h epatitis C viral (HCV) genotypes 1a/I and Ibm, hepatic interferon-alpha rec eptor (IFNAR) mRNA expression correlated with response to IFN therapy, leve ls 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 +/- 0.6, n = 5) was s ignificantly higher than for the nonresponding group (0.059 +/- 0.01, n = 1 5) (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 correlat ion between the amounts of IFNAR with (1) the total HAI (low HAI less than or equal to 7, IFNAR 0.076 +/- 0.013, n = 10; high HAI greater than or equa l to 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 Uni ted States with predominant genotypes 1a/I and 1b/II appears to correlate w ith response to IFN therapy and a low HCV RNA titer but not with the total HAI or its components.