• Phase I - To evaluate the prevalence of insulin resistance in patients with hepatitis C without cirrhosis and compare it to that observed in patients with hepatitis B also without cirrhosis.
  
• Phase II - Interventional phase - To evaluate the effect of anti-viral therapy on insulin resistance, determined by the OGTT method, in patients with hepatitis C found to have insulin resistance pre-treatment.
  
• - To evaluate the safety, efficacy and tolerability of Pegasys (peginterferon alfa-2a) given in combination with Copegus (ribavirin) given for 24 weeks or 48 weeks in treatment naïve patients with chronic hepatitis C (CHC).
  

Inclusion Criteria:

• patients attending Liver Clinic at Toronto Western Hospital, Toronto, ON, Canada
• Male and female patients
• Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
• Detectable serum HCV-RNA
• Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug
• All fertile males and females receiving Copegus must be using two forms of effective contraception during treatment and during the 6 months after treatment end
• All patients should have insulin resistance (>2.1) determined by the homeostasis model assessment (HOMA) method.

Exclusion Criteria:

• Women with ongoing pregnancy or breast feeding
• Therapy with any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) < 6 months prior to the first dose of study drug
• Any investigational drug < 6 weeks prior to the first dose of study drug
• Co-infection with active hepatitis A, hepatitis B and/or human immunodeficiency virus (HIV)
• History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
• Signs or symptoms of hepatocellular carcinoma
• History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
• Neutrophil count <1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening
• Serum creatinine level >1.5 times the upper limit of normal at screening
• History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease
• History of a severe seizure disorder or current anticonvulsant use
• History of immunologically mediated disease, chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
• History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
• Evidence of severe retinopathy (e.g. CMV retinitis, macula degeneration)
• Evidence of drug abuse (including excessive alcohol consumption) within one year of study entry
• Inability or unwillingness to provide informed consent or abide by the requirements of the study
• Cirrhosis on liver biopsy
• Type II diabetes mellitus
• Diabetogenic medications including steroids
• Current daily alcohol use of greater than 20 gm
• Known hypersensitivity to any of the contents of the study drug
• Patients currently participating in other Clinical Trials
• Patients previously treated for hepatitis C / received alfa-interferon

Additional exclusion criteria for patients receiving Copegus:

• Male partners of women who are pregnant
• Hgb <12 g/dL in women or <13 g/dL in men at screening
• Any patient with an increased baseline risk for anemia (e.g. thalassemia, spherocytosis, history of GI bleeding, etc) or for whom anemia would be medically problematic
• Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with Copegus therapy) would not be well-tolerated