To investigate the intra-hepatic activation of the IFN system in patients affected by chronic HCVinfection in comparison with that observed in a non-infectious liver disease such as nonalcoholic steatohepatitis, we measured the liver steady state mRNA levels of interferon-α, interferon-β and interferon-γ as well as of IFN-related genes (IFNAR-1, STAT1α, PKR, 2-5 AS, IRF-1, ICE and IL-18). In HCV-infected subjects, possible correlations of these parameters with viral load and liver injury were also analyzed. Twenty-four chronic untreated HCV-infected subjects and seven patients with non-alcoholic steatohepatitis were enrolled in the study. Liver biopsies were graded according to Knodell scores. Intra-hepatic mRNA levels of IFNs and related genes were assessed by semi-quantitative RT-PCR. In comparison with non-alcoholic steatohepatitis, in HCV-infected subjects IFN-α and -β mRNA levels were significantly lower, whereas IFN-γ, IFNAR-1, STAT1α IRF-1, and IL-18 mRNA were upregulated. Moreover, IFN-γ mRNA steady state levels were correlated positively with those of IFNAR-1, IRF-1, and IL-18, suggesting a coordinated induction of these genes. Although plasma viral load was correlated inversely with IL-18-specific mRNA, viral load was not related to liver injury. IFN-γ and IRF-1 mRNA levels were correlated positively with ALT, but not with the grading or staging. Conversely, IFN-α and -β mRNA levels were higher in livers with lower staging scores. These findings support the hypothesis that in chronic HCV infection there is an imbalance between an upregulated IFN-γ system and a downregulated IFN-α and -β system, probably due to a mixed effect exerted by HCV-specific and inflammatory non-specific factors.
- Liver injury
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