Retreatment of Chronic Hepatitis C Non-responders With Pegylated Interferon Alpha Plus Ribavirin Plus Pioglitazone

Inclusion Criteria: * Histologically confirmed chronic hepatitis C as per liver biopsy performed during the 12 months prior to enrollment (except patients with histologically proven cirrhosis or a Actitest/Fibrotest assay, or a Fibroscan performed during the 12 months prior to enrollment) * HCV RNA in serum \>600 IU/ml * elevated ALT * HCV genotypes 1, 2, 3 or 4 * failure to respond to a prior treatment with a pegylated interferon alpha + ribavirin * HOMA score \> 2.00 * documentation that sexually active female patients of childbearing potential are practicing adequate contraception (intrauterine device, oral contraceptives, progesterone implanted rods, medroxyprogesterone acetate, surgical sterilization plus a barrier method \[diaphragm + spermicide\] or monogamous relationship with a male partner who has had a vasectomy or is using a condom + spermicide) during the treatment period and for 6 months after discontinuation of therapy. A serum pregnancy test obtained at entry prior to the initiation of treatment must be negative. Female patients must not be breast feeding * documentation that sexually active male patients are practicing acceptable methods of contraception (vasectomy, use of a condom + spermicide, monogamous relationship with a female partner who practices an acceptable method of contraception) during the treatment period and for 6 months after discontinuation of therapy * willingness and capability to give written informed consent and to comply with the requirements of the trial Exclusion Criteria: * history of diabetes (ADA definition) * history of significant cardiovascular disease (NYHA III) including but not limited to uncontrolled hypertension, angina pectoris, myocardial infarction, coronary artery surgery and congestive heart failure * HBsAg and/or HIV * auto-immune disease, including auto-immune hepatitis * alcohol consumption exceeding 40 grams per day * hepatocellular carcinoma * renal insufficiency (serum creatinine levels above 200 micromol/l) * unconjugated bilirubin blood level \> 100 micromol/l * glutamyl transferase \> 20 times the ULN * prothrombin time \< 60% of control (except in case of oral anti-coagulant therapy) * neutrophil count \< 1.5 G/L * platelet count \< 70 G/L * hemoglobin \<120 g/L * organ or bone marrow transplantation * current neoplasm and/or anti-tumor chemotherapy * current hepatic arterial thrombosis * pregnant or breast feeding women; child bearing potential women without adequate contraception throughout the course of therapy * psychosis or anti-depressant therapy for uncontrolled clinical depression * epilepsy * clinically significant retinal abnormalities * thyroid dysfunction * drug abuse or substitution therapy during the 12 months prior to inclusion * interstitial pneumonitis * previous auto-immune hemolysis and all causes of chronic hemolysis