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