A phase III, randomised, multicentre, dose escalation, efficacy and safety study examining the effects of treatment with peginterferon alfa-2a with Child's A or B cirrhosis in Chronic Hepatitis C virus infection

INTERVENTION: Intervention: PEG‐IFN ‐ 90 mg subcutaneously (sc) once weekly for one month, 135 mg sc once weekly for one month, rising to 180 mg thereafter as tolerated in 1 ml solution administered sc once weekly for a total of 48 weeks. Control: conventional management. CONDITION: Liver cirrhosis in Hepatitis C Virus infections. ; Digestive System ; Liver cirrhosis in Hepatitis C Virus infections. PRIMARY OUTCOME: 1. Combined endpoint of non‐detectable serum HCV‐RNA (less than 100 copies/ml by the AMPLICORä Polymerase Chain Reaction [PCR] assay) at the end of the 24 week treatment‐free follow‐up period; 2. Death; 3. Liver transplantation (or need for); 4. Hepatocellular cancer SECONDARY OUTCOME: 1. End‐of‐treatment virological and biochemical responses; 2. Bleeding varices; 3. Ascites; 4. Spontaneous bacterial peritonitis and other infections; 5. Encephalopathy; 6. Quality of life as measured by the SF 36 and Fatigue Severity Scale INCLUSION CRITERIA: To be eligible for this trial, patients must have documentation of the following: 1. Aged over 18 years 2. Serologic evidence of Hepatitis C Virus (HCV) infection by an anti‐HCV antibody test 3. Qualitative evidence of infection with HCV Ribonucleic Acid (RNA) 4. Chronic liver disease consistent with chronic hepatitis C infection on a biopsy as judged by a local pathologist 5. Patients must have had an abdominal ultrasound, Computed Tomography (CT) scan, or Magnetic Resonance Imaging (MRI) scan with evidence of cirrhosis, but without evidence of hepatocellular carcinoma (within two months of randomisation) and a serum alphafetoprotein (AFP) less than 100 ng/ml. Patients with elevated AFP should have evidence of no increase of more than 10 KIU/l for three months prior to entry 6. Negative urine pregnancy test (for women of childbearing potential) documented within the 24‐hour period prior to the first dose of test drug. Additionally, all fertile mal