Rosina 1991

Methods	Sample size: not calculated. Intention‐to‐treat: yes.
Participants	Patients with chronic hepatitis D (n =61) from Italy. Inclusion criteria: positive HDV antibody, elevated ALT for one year, histological evidence of chronic hepatitis or cirrhosis, and positive staining for HDAg on liver Bx done within six months . Exclusion criteria were: previous interferon therapy, decompensated cirrhosis, concomitant severe illness, proven drug abuse, prothrombin time greater than 4 s prolonged, platelets < 100,000/cmm, WBC < 3000/cmm, granulocytes < 1500/cmm, creatinine > 1.7 mg/dl, anti‐HIV antibodies.
Interventions	Control: no treatment (n = 30). Experimental 1: interferon alfa‐2b 5 million units (MU) t.i.w. for 4 months, 3 MU thrice a week for 8 months.Duration: 1 year (n = 31). Follow‐up: 1 year post treatment. Liver biopsy at enrolment and second month of post treatment follow‐up.
Outcomes	Normalisation of ALT. Improvement in liver histology. Decrease in HDAg in liver biopsy. Loss of HDV RNA.
Notes	Drop outs/withdrawals = 13; 5 from the treatment group and 8 from no treatment. Reasons were ulcer at the injection site in1, acute icteric hepatitis in 1, and non‐compliance 3 in the treatment group and 8 in the control group. Intention‐to‐treat analysis done. However, authors preferred per protocol analysis for the histological improvement.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote "Study patients were randomly assigned to the treatment or control group (no placebo) using a computer‐generated randomisation code."
Allocation concealment (selection bias)	Unclear risk	Not mentioned.
Blinding (performance bias and detection bias) All outcomes	High risk	Unblinded trial design.
Incomplete outcome data (attrition bias) All outcomes	High risk	There were thirteen (out of 61 patients) dropouts during study period. Quote "Of these 61 patients, 48 (79%) have completed 24 months of the study"
Selective reporting (reporting bias)	Low risk	Outcome measures adequately reported.