Scotto 2005.

Methods	Randomised clinical trial with three parallel‐group design. Sample size calculation: not described. Intention‐to‐treat analysis: used.
Participants	Country: Italy. Number of participants randomly assigned: 78; 36 men and 42 women. All participants were treatment‐naive. All participants were infected with HCV genotype one‐b. Mean histological activity index score was 13.7 ± 2.9 in peginterferon plus ribavirin group, 13.7 ± 3.8 in lower‐dose interferon plus ribavirin group, and 13.9 ± 3.2 in higher‐dose interferon plus ribavirin group. Inclusion criteria. Serum ALT levels at least twice the upper normal limit for at least six months before treatment. Presence of anti‐HCV antibodies determined by means of a third‐generation enzyme‐linked immunosorbent assay (HCV ELISA, Ortho Diagnostic System, Raritan, NJ, USA) and confirmed by additional third‐generation recombinant immunoblot assay (RIBA, Ortho Diagnostic System, Raritan, NJ, USA). Presence of measurable serum HCV RNA (Cobas Amplicor HCV Monitor test, Roche Molecular System, Basel, Suisse). HCV genotype one‐b (Inno‐Lipa HCV II Kits, Innogenetics, Zwijmaarden, Belgium). Leukocyte counts greater than 3000/mm3. Platelet counts greater than 75,000/mm3. Haemoglobin concentration greater than 13 g/dL for men and greater than 12 g/dL for women. Liver biopsy performed within one year of the start of treatment with histological diagnosis of chronic hepatitis based on the histological activity index score as described by Knodell et al. and modified by Ishak et al. Exclusion criteria. Previous episodes of decompensated liver disease (i.e., ascites, bleeding from oesophageal varicose veins, encephalopathy). HIV coinfection. Active intravenous drug use. Potential cause of liver disease other than HCV.
Interventions	Participants were randomly assigned to three groups.: Group 1: peginterferon alpha‐2b 1.5 µg/kg for 52 weeks (n = 26). Group 2: interferon alpha‐2b 6 MU for 52 weeks (n = 26). Group 3: interferon alpha‐2b 3 MU daily for 52 weeks (n = 26). All participants also received ribavirin at 800 to 1000 to 1200 mg according to body weight (less than 65 kg, 65 to 85 kg, and more than 85 kg). Participants were followed up for 24 weeks after the end of treatment.
Outcomes	Primary outcomes were early, end of treatment, and sustained biochemical and virological responses. Other outcomes reported are histological changes, adverse events, and treatment discontinuations.
Notes	Follow‐up: Three participants discontinued treatment in peginterferon plus ribavirin group, four in lower‐dose interferon plus ribavirin group, and eight in higher‐dose interferon plus ribavirin group. Study author contacted for additional information, but no reply obtained.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Comment: Randomisation was performed using a matrix of casual numbers, which generated the random allocation sequence table.
Allocation concealment (selection bias)	Low risk	Comments: central allocation concealment.
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Comments: Blinding to the outcome assessor is not mentioned.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comments: Incomplete outcome data were addressed adequately.
Selective reporting (reporting bias)	Low risk	Comment: All clinically relevant and reasonably expected outcomes were reported.
Other bias	Low risk	Comment: The study seems to be free of other sources of bias.