Poupon 2000.

Methods	Generation of allocation sequence: unclear (no description). Allocation concealment: unclear (no description). Double blinding: adequate (identical placebo). Follow up: adequate (five and four patients withdrew from the combination and the monotherapy groups, respectively). Sample size calculation: no. Intention‐to‐treat analysis: yes.
Participants	Country: France. Type of hepatitis: chronic hepatitis C. INCLUSION CRITERIA ‐ age between 18 and 65 years; ‐ persistent serum ALT elevation higher than 1.5 times the upper normal limit for more than six months; ‐ serum anti‐HCV positive; ‐ histological confirmation in the year preceding inclusion; ‐ resistant to IFN on the basis of having received IFN at a dosage of at least three million units three times weekly for at least six months. EXCLUSION CRITERIA ‐ autoimmune hepatitis type I or type II, other autoimmune diseases; ‐ associated liver diseases, other serious illnesses, signs of intolerance to IFN during previous treatment, haemophilia and other constitutional coagulation disorders, serum creatinine higher than 150 µmol/l, polymorphonuclear neutrophils lower than 1000/µl, platelets lower than 80,000/µl, signs of decompensated cirrhosis; alcohol consumption more than 40 g/day; history of psychiatric illness or treatment with antidepressant drugs; human immunodeficiency seropositivity; drug addiction in previous year; pregnancy, and diabetes requiring treatment with oral antidiabetic drugs or insulin. PARTICIPANTS ‐ UDCA plus IFN group (n = 47): Mean age (years +/‐ SD) 45 +/‐ 2. Ratio of sex (M/F) 37/10. Proportion of patients with cholestasis: no information. Proportion of patients with cirrhosis: 14 patients. ‐ Placebo plus IFN group (n = 44): Mean age (years +/‐ SD) 52 +/‐ 1. Ratio of sex (M/F) 32/12. Proportion of patients with cholestasis: no information. Proportion of patients with cirrhosis: 14 patients.
Interventions	UDCA plus IFN group: UDCA ‐ Dose: 13‐15 mg/kg/day; ‐ Route: orally; ‐ Timing: two times per day; ‐ Duration: six months. Alpha IFN 2a ‐ Dose: three million units; ‐ Route: subcutaneously; ‐ Timing: three times per week; ‐ Duration: six months. Placebo plus IFN group: Alpha IFN‐2a ‐ Dose: three million units; ‐ Route: subcutaneously; ‐ Timing: three times per week; ‐Duration: six months.
Outcomes	‐ Normalisation of serum ALT at the end of treatment and follow‐up. ‐ Serum ALT, AST, GGT, and alkaline phosphatases activities and serum total bilirubin concentrations at the end of treatment and follow‐up. ‐ Absence of HCV RNA in serum at the end of treatment and follow‐up. ‐ Histological changes six months after cessation of IFN.
Notes	Follow‐up time: six months after stopping alpha IFN treatment.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear