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.

Interferon-alpha receptor 1 mRNA expression in peripheral blood mononuclear cells is associated with response to interferon-alpha therapy of patients with chronic hepatitis C

“…The differences in IFNAR1-mRNA levels in PBMC between responders and non-responders before IFN-α therapy were similar to those observed in liver biopsies from HCVinfected patients (14,17). It is likely that IFNAR1-mRNA expression in PBMC reflects the IFNAR1-mRNA status of the liver, as recently demonstrated for IFNAR2 (18).…”

“…Non-responders Controls the liver (13,14,17). Moreover, IFNARmRNA levels in liver were not correlated with serum ALT or 2',5'-oligoadenylate synthetase levels, viral load or HCV (11,17).…”

“…Absent or low intrahepatic IFNARmRNA levels are related to a poor response to IFN-α, to increased histological hepatitis activity and to the severity of liver fibrosis in patients with chronic hepatitis C (10)(11)(12). In addition, IFNAR-mRNA expression in liver is correlated negatively with HCV-RNA viral load and the presence of HCV genotype 1b in HCV-infected patients (13)(14)(15).…”

DNA Microarray Analysis of Chimpanzee Liver during Acute Resolving Hepatitis C Virus Infection

“…634,2000). Other studies have demonstrated that the IFN-␣/␤ receptor is down-regulated in HCV chronically infected patients (25,26,46). The importance of the host in IFN responsiveness was also demonstrated when the virus from an IFNunresponsive patient became responsive to IFN when transmitted to another individual (58).…”

Intrahepatic mRNA Levels of Type I Interferon Receptor and Interferon-Stimulated Genes in Genotype 1b Chronic Hepatitis C

“…Accordingly, the expression levels of various types of IFN receptor subunit genes and their ratios may have an infl uence on the levels of type I IFN-mediated signals and, thus, an association with IFN response. Several studies have suggested that in CH-C, high levels of IFNAR1 or IFNAR2 mRNA in the liver are related to a sustained virological response [5][6][7][8][9] , but no information is available on the infl uence of spliced variant forms of IFNAR2 on the effi cacy of IFN therapy. Furthermore, a recent study has reported confl icting results about the importance of IFNAR1 and IFNAR2 mRNA on response to IFN therapy [10] .…”