Effects of Genotypes on Interferon Signaling in Chronic Hepatitis C

Effects of Genotypes on Interferon Signaling in Chronic Hepatitis C

The objective of this pilot project is to investigate the prognostic criteria for sensitivity of Chronic Hepatitis C (CHC) Genotype 1, patients to IFNa treatment. Signal transduction in peripheral blood mononuclear cell (PBMC) of control groups will be compared with that of CHC patients. For this study, 20 patients with Hepatitis C virus (HCV) infection who are to undergo standard antiviral therapy and 10 healthy donors (significant others of the HCV subject) will be enrolled. Signal transduction will be studied in peripheral blood of CHC subjects before the treatment, after 1 and 3 months of treatment, and 4-6 months following the completion of treatment.

In addition, the mechanism of non-responsiveness of HCV patients to IFNa will be studied. For this purpose, formation of complexes between STAT1 and its negative regulator, PIAS1 (immunoprecipitation, Western blot) will be examined. In comparing subjects on standard therapy vs the addition of betaine, (under separate studies) we will assess whether the formation of STAT1-PIAS1 complexes is due to impaired methylation on STAT1 on arginine residues which may be over come by the addition of betaine.

Inclusion Criteria

• 19 years of age or older, of either gender
• History of chronic hepatitis C documented by HCVRNA or healthy family member/significant other
• Documented genotype 1 for hepatitis participants or no hepatitis infection for healthy control
• Subject prescribed antiviral therapy for hepatitis participants or none for healthy control
• Able to give informed consent

Exclusion Criteria

• Under 19 years of age
• Unable to give informed consent