Inclusion Criteria:

• Participants willing to give written informed consent and able to adhere to dose and visit schedules.
• Adult participants 18 years of age or older of either gender or any race. Participants who are over 65 years of age must be in generally good health.
• HCV-antibody (Ab) or HCV-RNA positive by polymerase chain reaction (PCR) for at least 6 months.
• Serum positive for HCV-RNA by PCR assay.
• Subjects must be previous nonresponders or relapsers on pegylated interferon and ribavirin therapy.
• Liver biopsy within 24 months prior to enrollment into the protocol.

• Compensated liver disease with the following minimum hematological, biochemical, and serologic criteria at the Screening Visit (WNL = within normal limits):

  • Hemoglobin values of < 12 gm/dL for females and < 13 gm/dL for males.
  • White blood cells (WBC) < 3,000/mm3
  • Neutrophil count < 1,500/mm3
  • Platelets < 65,000/mm3
  • Direct bilirubin, within 20% of upper limits of normal (ULN)
  • Indirect bilirubin, (WNL) (unless non-hepatitis related factors such as Gilbert's disease explain an indirect bilirubin rise. In such cases indirect bilirubin must be < 3.0 mg/dL [< 51.3 µmol/L]).
  • Albumin > 3 gm/dL
  • Serum creatinine < 20% of ULN
  • Thyroid stimulating hormone (TSH) WNL
  • Alpha fetoprotein value < 100 ng/mL.
• Reconfirmation and documentation that sexually active female subjects of childbearing potential are practicing adequate contraception during the treatment period and for 6 months following the last dose of study medication. Female subjects must not be breast-feeding.
• Reconfirmation that sexually active male subjects are practicing two acceptable methods of contraception during the treatment period and for 6 months following the last dose of study medication.

Exclusion Criteria:

• Inability or unwillingness to provide informed consent or abide by the requirements of the study
• Participants on insulin are excluded.
• Participants on metformin or another thiazolidinedione must have a three-month wash-out period to be considered for the study.
• Women who are pregnant or breast-feeding
• Males whose female partner is pregnant
• No other thiazolidinedione after liver biopsy and/or during the entire study (other than those subjects randomized to receive rosiglitazone during the study)
• Hepatitis C of non-genotype 1
• Suspected hypersensitivity to interferon, ribavirin, or rosiglitazone

• Any cause for liver disease other than chronic hepatitis C, insulin resistance, or non-alcoholic fatty liver disease (NAFLD), including but not limited to:

  • Hemochromatosis
  • Alpha-1 antitrypsin deficiency
  • Co-infection with hepatitis B virus (HBV) [serum hepatitis B surface antigen (HBsAg) positive]
  • Wilson's disease
  • Autoimmune hepatitis
  • Alcoholic liver disease (consumption of greater than 2 drinks a day on average)
  • Drug-related liver disease
• Any condition that would prevent the subject from having a liver biopsy.
• Hemoglobinopathies that could potentially compromise patient safety (e.g., beta thalassemia major, sickle cell disease)
• Evidence of advanced liver disease
• Participants with organ transplants other than cornea and hair transplant

• Any known preexisting medical condition that could interfere with the subject's participation in and completion of the protocol such as:

  • Preexisting psychiatric condition, especially severe depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt.
  • Participants with a history of mild depression may be considered for entry into the protocol provided that a pretreatment assessment of the subject's mental status supports that the participant is clinically stable.