The purpose of this study is to test whether the correction of insulin resistance with pioglitazone, will improve the response to antiviral treatment.

In patients infected with genotypes 1, 4, 5 and 6, the response rate to antiviral therapy remains suboptimal (less than one in two patients have a sustained virological response), which justifies the search for strategies optimizing the results of antiviral therapy. Some factors associated with non response have been identified. Among the modifiable factors, numerous series have shown that insulin resistance adversely impacts the rate of sustained virological response. The aim of this study is to determine whether the pharmacological correction of insulin resistance through therapy with glitazones restores higher rates of viral eradication and to determine the impact on the kinetics of viral response. Patients will be randomized to receive pioglitazone or placebo starting 4 months before initiating pegylated interferon and ribavirin and continued throughout the whole antiviral treatment period.

• Chronic Hepatitis C
• Insulin Resistance

• Drug: Pioglitazone
  Pioglitazone, 45 mg QD (30 mg QD the first month)
• Drug: Placebo
  Placebo 45 mg QD (30 mg QD the first month)

• 1: Active Comparator
  Pioglitazone, 16 weeks before and during antiviral combination therapy
  Intervention: Drug: Pioglitazone
• 2: Placebo Comparator
  Pioglitazone placebo, 16 weeks before and during antiviral combination therapy
  Intervention: Drug: Placebo

Inclusion Criteria:

• 18 years old or older
• Chronic HCV infection documented by PCR with genotype HCV-1, 4, 5 or 6
• Naive Patient(never treated with antivirals for HCV)
• HOMA score higher than 2.5
• Patient for which the investigator decided to start antiviral treatment for chronic hepatitis C

Exclusion Criteria:

• Cardiovascular disease: heart failure stage NYHA II, III or IV, unstable angina, myocardial infarction in the previous year, cardiac surgery or stroke
• Alcohol consumption exceeding 40 g / day
• Decompensated liver disease: Child-Pugh B 8 or higher, or one of the following : bilirubin over 35 mol / L, TP below 50%, ascites, encephalopathy
• Hepatocellular carcinoma or any other neoplasm (except if in remission for > 5 years)
• Other documented chronic liver disease
• Insulin treated diabetes
• HBV or HIV co-infection infection confirmed
• Thrombocytopenia below 50 000/mm ³; neutropenia below 750/mm ³ or hemoglobin below 11 g / dL
• Drug-induced steatosis(tamoxifen, gluco-corticosteroids, amiodarone, tetracyclines).
• Bone marrow or solid organ transplantation
• Pregnancy or breastfeeding, or desire for pregnancy during the study period.
• Patients under legal protection or unable to express their consent