Bruno 2004.

Methods	Randomised clinical trial with two parallel‐group design. Sample size calculation: performed, 151 participants estimated for each group. Intention‐to‐treat analysis: not used, although stated.
Participants	Country: Italy. Number of participants randomly assigned: 323; 194 men and 117 women, and 12 excluded from analyses. All participants were treatment‐naive. All participants were infected with HCV genotype one. Inclusion criteria. Previously untreated HCV RNA positive patients between 18 and 65 years of age with ALT values above 1.5 times the upper normal limit. Liver biopsy performed within six months before enrolment and a diagnosis of chronic hepatitis with any degree of fibrosis. Haemoglobin equal to 13 g/dL for males, equal to 12 g/dL for females, WBC count greater than 3000/mm3, granulocyte count greater than 1500/mm3, platelet count greater than 80,000/mm3, bilirubin, albumin and serum creatinine levels within normal limits. Exclusion criteria. Advanced cirrhosis, that is, large oesophageal varices (F2 or more), history of gastrointestinal bleeding, ascites or encephalopathy. Hepatocellular carcinoma. Anti‐HIV or HBsAg positivity. Alcohol abuse (equal to 80 mg/d). Parenteral drug addiction if not abstaining for at least two years; and any other contraindications to interferon or ribavirin.
Interventions	Participants were randomly assigned to two groups. Group 1: peginterferon alpha‐2b 100 µg for weight 65 kg or greater and 80 µg for weight below 65 kg, for the first eight weeks, followed by a fixed dose of 50 µg for the next 40 weeks plus ribavirin for 48 weeks (n = 163). Group 2: non‐pegylated interferon alpha‐2b 6 MU plus ribavirin for 48 weeks (n = 148). For both groups, ribavirin was given at a dose of 1000 mg for participants weighting 75 kg or less and 1200 mg for those weighing more than 75 kg. Participants were withdrawn from treatment if they did not achieve a virological response that was defined as undetectable serum HCV RNA by PCR 24 weeks after starting treatment.
Outcomes	Primary outcome was sustained virological response, defined as the absence of detectable HCV RNA by PCR 24 weeks after the end of treatment. Other outcomes reported are end of treatment biochemical and virological response, sustained biochemical response, and frequency of discontinuations and dose reductions with causes. Limit for hepatitis C virus RNA detection was 50 IU/mL.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: computer‐generated scheme. Patients were stratified according to centre and randomised in blocks of four to the peginterferon plus ribavirin or interferon plus ribavirin group.
Allocation concealment (selection bias)	Low risk	Comment: central randomisation centre.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Comment: It is mentioned only that the slides of liver biopsy specimens were coded and read by a single pathologist, who was unaware of clinical data.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: The number of participants lost to follow‐up is mentioned. Treatment was discontinued in 31 and 46 participants in peginterferon plus ribavirin and interferon plus ribavirin groups.
Selective reporting (reporting bias)	Low risk	Comment: All clinically relevant and reasonably expected outcomes were reported.
Other bias	Unclear risk	Comment: Conflict of interest bias might be present. Schering‐Plough Italy supplied peginterferon alpha‐2b, and the other drugs were provided by the National Health System.