Study of Long-term Peg Intron vs. Colchicine in Non-responders.

Inclusion Criteria

• *Adult male or female, age 18 to 75 years
• HCV RNA positive by PCR
• Previous treatment with at least three months of interferon or interferon / Ribavirin. Patients should have had no interferon for at least 2 months prior to enrollment.
• Non-responders are identified by failure to clear virus by PCR after a minimum 3-month course of treatment and who have been off treatment for at least 2 months with a positive PCR for HCV prior to entry into the current study, 2) Partial responders have a reduction of 1 long in HCV RNA, but the virus is still detectable, 3) Breakthrough patients have been negative on treatment, but virus appeared while still on treatment, 4) Relapsers are defined as negative PCR at some point during treatment, but virus reoccurred or was detectable by HCV PCR when treatment stopped.

Patients should have had a liver biopsy showing at least Stage 3 disease prior to being considered for this study. A baseline liver biopsy is necessary for inclusion in the study. Baseline liver biopsies can be performed within six months of entering the study.

In patients with cirrhosis and endoscopic evidence of portal hypertension, a biopsy within the last 2 years is acceptable as the baseline biopsy. For patients with established cirrhosis on liver biopsy and no portal hypertension, a biopsy within 12 months can be used as the baseline biopsy if it is available for evaluation by the Pathology core. All these patients will still require liver biopsy at 2 years and 4 years. The decision to biopsy at 2 and 4 years is also a clinical decision and in the presence of clinical progression or coagulopathy, or where there may be a risk from liver biopsy, the Investigator should call the PI, Dr. Afdhal for a waiver of biopsy. Patients with Ishak Stage 3 and 4 require a biopsy within 6 months of randomization.

• Hemoglobin >= 11 g/dl in males and 10 g/dl in females
• Neutrophil count > 1,500/mm3
• Platelets > 50, 000/mm3

Platelet count: For standard dose of PEG-Intron 0.5mcg/kg platelet count must be greater than 70,000. Patients with platelet count 50 - 70,000 can start at 0.25mcg/kg for weeks 0 - 4. If platelets fall to less than 30,000, stop treatment. If platelets remain > 50,000 at week 4, PEG-Intron can be increased to 0.5mcg/kg. Patients randomized to Colchicine with platelets 50,000 - 70,000 can be started at standard dose 0.6mg bid po with standard dose reduction.

• Prothrombin time 2.8mg/dl)
• Serum creatinine 100 ng/ml either a triple phase contrast CT scan or MRI with gadolinium must show no focal mass or evidence of HCC
• Ultrasound with no evidence of focal mass suggestive of hepatoma (within 6 months of informed consent).
• Documentation that sexually active female patients of childbearing potential are practicing adequate contraception during the treatment period. A urine 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 during the treatment period.
• Written informed consent specific for this protocol has been obtained prior to entry.

Exclusion Criteria

• Any cause of liver disease based on patient history and biopsy (where applicable) other than chronic hepatitis C including but not limited to:
• Co-infection with hepatitis B or HIV
• Hemochromatosis (confirmed by genetic testing)
• Alpha-1 antitrypsin deficiency
• Wilson's disease
• Renal or liver transplant patients
• Autoimmune hepatitis
• Alcoholic liver disease
• Obesity induced liver disease
• Drug related liver disease

In addition:

• Evidence of decompensated liver disease such as a history or presence of ascites, and spontaneous encephalopathy. Patients with past bleeding esophageal varices that have not bled for more than 1 year can be included.
• Hypersensitivity to alpha interferon
• Drug related liver disease
• Hemoglobinopathies (e.g. Thal