Blitzer 1977

Methods	A prospective, double‐blind randomised trial Country: USA, 1971‐1973 Analyses were not performed according to the intention‐to‐treat principle. Sample size calculation was not reported
Participants	Demographic characteristics Age (mean): prednisolone/placebo group 47.2/48.4 Sex: male (all participants) "There were no significant differences between them with respect to mean age, sex, race, duration of hospitalization prior to entry into the study, frequency of histologically proved cirrhosis, or to the histologic severity of the alcoholic hepatitis." Inclusion criteria and degree of severity ".. patients with alcoholic hepatitis who met the following criteria after at least five days in the hospital were included in the study: (1) recent history of heavy alcohol consumption (more than one pint of whiskey per day or its alcoholic equivalent); (2) hepatomegaly based on physical examination (palpable more than 5 cm below the costal margin) and/or liver scan; (3) total serum bilirubin greater than 5 mg/100 mL; and (4) at least two of the following abnormalities: (a) serum glutamic oxaloacetic transaminase (SGOT) greater than 100 Reitman‐Frankel units per ml, (b) serum albumin concentration less than 3g/100 mL, or (c) prothrombin time more than 2 s greater than control value. Liver biopsies were performed whenever possible, but were not required for admission to the study." "14 biopsies proved alcoholic hepatitis." "Neither positive PPD skin tests nor active tuberculosis excluded patients from randomization. None of the former were encountered, and one of the latter continued to receive INH and PAS throughout the study. If serious life‐threatening infection was present, patients' entry into the protocol was postponed until it was eradicated. Patients with either a history of peptic ulcer, active peptic ulcer disease, or gastrointestinal bleeding were included." The study authors did not clearly describe the degree of severity of alcoholic hepatitis; however, the participants probably had moderate to severe alcoholic hepatitis, since they presented patients with alcoholic hepatitis who met the described criteria. Exclusion criteria "...who had been treated with adrenocorticosteroid in the six months prior to admission or who showed evidence of psychotic behavior precluding their cooperation during the investigation were excluded". Randomisation procedure "... Patients were assigned by random, sealed‐envelope technique to receive either placebo or steroid". Number of participants randomised n = 33 Prednisolone group: n = 17 Placebo group: n = 16
Interventions	Experimental group: oral prednisolone Dose: "10 mg q.i.d [four times a day], for 14 days, 5 mg qid [four times a day] for 4 days, 2.5 mg qid [four times a day] for 4 days, and 2.5 nag bid [four times a day] for 4 days" Control group: placebo tablets Dose: the same dosage schedule as the prednisolone group Additional interventions to the trial groups: "Patients were encouraged to eat the standard hospital 2600‐calorie diet and were offered supplements when caloric intake seemed inadequate. Low‐protein, low‐sodium, and other special diets were employed as the clinical situation dictated." Duration of treatment: 26 days Follow‐up after randomisation: 9 weeks
Outcomes	The trial outcomes were: Mortality Liver biochemistry Liver histology Adverse events
Notes	Letter sent to authors in March 2000. No answer received. No further attempts were made as the trial was conducted between 1971‐1973. One participant received placebo treatment during the trial. At the end of the therapy, due to lack of improvement, the ward physician requested the code be broken. The participant received a 7‐day course of prednisolone. He died 17 days later; his death was included in the mortality data of the placebo group on an intention‐to‐treat basis. On the 26th day treatment period, three participants in the placebo group and one in the glucocorticosteroid group received the alternative medication on a double‐blind basis. "Both prednisolone and placebo tablets were kindly supplied by the Upjohn Co., Kalamazoo, Michigan."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Patients were assigned by random, sealed‐envelope technique to receive either placebo or steroid"
Allocation concealment (selection bias)	Low risk	"Patients were assigned by random, sealed‐envelope technique to receive either placebo or steroid"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Only the pharmacist was aware of the type of therapy which any individual patient was receiving."
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information was provided
Incomplete outcome data (attrition bias) All outcomes	High risk	"5 participants, who had each received less than 5 days of therapy, were subsequently excluded from analysis. Of these, three had left the hospital against medical advice or withdrew from the study, and in two participants experimental therapy had been stopped following gastrointestinal haemorrhage. One bled after 4 days of therapy from a gastric varix and the other from an unknown site after three days of treatment. On breaking the code at the end of the investigation, it was learned that all five participants had been in the steroid group....Furthemore, the addition of two deaths among the five excluded participants ......" 3/17 people in the prednisolone group and 0/16 people in the placebo group dropped out (9%)
Selective reporting (reporting bias)	Low risk	All‐cause mortality, serious adverse events, and liver‐related mortality were reported
For‐profit bias	Unclear risk	Prednisolone and placebo tablets were supplied by the Upjohn Co., Kalamazoo, Michigan.
Other bias	Low risk	None suspected