Carithers 1989.

Methods	Randomised, multicentre, double‐blind, placebo‐controlled, clinical trial Country: USA Dates: 1979–1984 Intention‐to‐treat analysis: yes Sample size calculation: reported (calculated that 62 patients should be entered to have 95% chance of detecting a difference in survival between the 2 groups).
Participants	Demographic characteristics Age (mean): methylprednisolone group: 43.1 (SD 2.0) years; control group: 44.4 (SD 1.7) years Sex: methylprednisolone group: 20 (57%) men; control group: 21 (68%) men Inclusion criteria and degree of severity History of long‐standing alcoholism and clinical features of alcoholic hepatitis evaluated by 1 principal investigator within 3 days of admission; clinical evidence of spontaneous hepatic encephalopathy (assessed using standard clinical criteria and present when correctable causes of encephalopathy had been excluded) or a discriminant function value > 32 or both; negative hepatitis B surface antigen within the first 3 days of hospitalisation; and no history of previous viral hepatitis Exclusion criteria Gastrointestinal haemorrhage requiring transfusions; diabetes requiring insulin administration; active infection requiring treatment; clinical and laboratory evidence of acute pancreatitis; history of recent head trauma; known prior heroin addiction; or pre‐existing chronic renal disease with a serum creatinine > 175 mmol/L Randomisation procedure Random code sequence generated and kept by an independent source (see 'Risk of bias' table) Number of participants randomised: 67 Prednisolone group: n = 36 (2 refused, 1 was excluded from analysis); 33 analysed Control group: n = 31
Interventions	Experimental group: methylprednisolone 32 mg/day (equivalent to 40 mg prednisolone). Single dose of 8 tablets of 4 mg each morning for 28 days. In participants unable to take oral medications, intravenous infusions of study drug administered daily (methylprednisolone sodium succinate (SoluMedrol) or identical placebo. After 4 weeks, 4 tablets administered daily for 1 week followed by 2 tablets daily for 1 week; then therapy discontinued. Control group: placebo; identical tablets Additional treatment: participants offered 3000‐caIorie diet. Protein (1–1.5 g/kg bodyweight) provided when no evidence of hepatic encephalopathy. Protein restricted to ≤ 20 g/day and lactulose therapy instituted in participants with signs of hepatic encephalopathy. Ascites managed with sodium restriction or by addition of spironolactone in participants who did not respond with diuresis within 5 days. Fluid intake restricted in participants with hyponatraemia. B‐compIex multivitamins and folic acid 1 mg given daily. Participants who developed tremulousness or delirium tremens received diazepam or oxazepam. Duration of treatment: 5 weeks; 28 days at 32 mg/day then 16 mg/day for 7 days Duration of follow‐up after randomisation: at discharge
Outcomes	Mortality Liver biochemistry Adverse events
Notes	Letter sent to authors in March 2000. No answer received
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "… Random sequences for drug or placebo were submitted to the Upjohn Company (Kalamazoo, Michigan), which provided methylprednisolone (Medrol) in 4‐mg tablets and identical placebo tablets as well as intravenous preparations of methylprednisolone sodium succinate (SoluMedrol) and placebo. A random code was prepared for each of the four participating institutions such that within each group of 10 patients, 5 would receive methylprednisolone and 5 placebo. The random code sequence was kept by an independent source."
Allocation concealment (selection bias)	Low risk	Quote: "the random code sequence was kept by an independent source."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "neither the principal investigators nor their associates were aware of which regimen patients received throughout the trial."
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "Data obtained at initial evaluation and follow‐up were recorded on standardized data collection forms that were submitted to the statistical coordinating center at the end of each study … A study overview committee, chaired by Dr. Hyman Zimmerman, reviewed the ongoing results of the study on a yearly basis from reports generated by the statistical coordinating center, which had access to the randomisation codes."
Incomplete outcome data (attrition bias) All outcomes	Low risk	3% Quote: "One patient who received methylprednisolone was belatedly discovered to have had neither encephalopathy nor elevation of discriminant function sufficient to meet the entry criteria and was excluded from analysis. Of the remaining 66 patients, 64 remained in the hospital for the duration of the study. Two methylprednisolone recipients refused to continue in the study. The first patient signed out of the hospital after 10 days on the trial and was alive at the end of the study. The second patient was discharged at his insistence after 15 days on the trial and was given the study drug to take at home, but he never returned for follow‐up. His status at the end of the study was unknown. He was the only patient lost to follow‐up." Prednisolone group: 2/36; control group: 0/31
Selective reporting (reporting bias)	Low risk	No protocol available. However, all‐cause mortality, serious adverse events, and liver‐related mortality were reported.
Other bias	Low risk	Not suspected