Porter 1971

Methods	A prospective, double‐blind, controlled pilot trial Country: USA Analyses were not performed according to the intention‐to‐treat method. Sample size calculation was not reported.
Participants	Demographic characteristics steroid/placebo group Age (years) 44.6 + 4.4/49.5 + 8.9 (age range 27 to 61 years) Sex: male 13/7 (64%/67%) Inclusion criteria and degree of severity: "A history of recent heavy alcohol ingestion a serum bilirubin concentration of 5 mg per 100 mL or more clinical and laboratory deterioration over the first five hospital days, a striking lack of improvement in the patient's clinical and biochemical status over the same period, or rapid marked deterioration in less than 24 hours for admission to the study all three absolute criteria were required In addition, two or more major criteria or one major and four or more minor criteria had to be met. The major criteria were liver biopsy showing alcoholic hepatitis; hepatic encephalopathy (including asterixis); persistent or progressive azotaemia not explained by another process, and total bilirubin levels > 20 mg/100 mL. The minor criteria for inclusion were fever that was not obviously secondary to another process; white blood count > 12,000 not obviously secondary to another process; anorexia or nausea or vomiting; palpable hepatomegaly; palpable splenomegaly; oesophageal varices; spider angiomas, edema or ascites; palmar erythema and a prothrombin time prolonged three or more seconds over control. The Australia antigen was absent from the serum of all 16 patients in whom it was sought. Before the trial, a percutaneous needle biopsy of the liver was performed if the prothrombin time was not prolonged more than four seconds over control and there was no clinical bleeding tendency. Exclusion criteria active gastrointestinal bleeding, pancreatitis, radiological evidence of peptic‐ulcer disease, active or questionably active pulmonary tuberculosis and potentially life threatening bacterial infection. Randomisation procedure: "the case was randomised into one of the two treatment groups. Both the steroid (6‐ methyl prednisolone, or Medrol) and the placebo (lactose) were packaged and coded by number in both parenteral and oral forms (prepared and supplied through the courtesy of the Upjohn Co, Kalamazoo,Mich)and randomisation was achieved by a number drawn from a pool. Neither patients nor physicians knew which form of treatment was used until the study had been completed, when the code was broken." Number of participants randomised: n = 23 (20) "23 accepted to participate, but 3 died within 36 hours of the start of therapy, and were excluded from the analysis before the code was broken, and did not receive adequate medication. The final series consisted of 20 patients" Prednisolone group: n = 11 Placebo group: n = 9
Interventions	Prednisolone group: "6‐methyl‐prednisolone (or Medrol) 40 mg per day (equivalent to 50 mg prednisolone, or 200 mg hydrocortisone) in three divided doses, parenterally for the first 10 days. If clinical improvement occurred over this interval and if nausea and vomiting were absent the drug was administered orally, and the dose gradually tapered (decreased every second day by 4 mg for the 11th to the 18th days, by 2 mg for the 19th to 30th days and every third day by 2 mg for the 31st to 45th days). If there was no clinical improvement within 10 days. The initial parenteral dose of 40 mg daily was continued until improvement or death occurred." Dose: 50 mg prednisolone Placebo group: placebo(lactose). "...packaged and coded by number in both parenteral and oral forms (prepared and supplied through the courtesy of the Upjohn Co, Kalamazoo, Mich)" Additional treatment: "early in the study only the patients with a positive intermediate strength PPD test or a suspicious chest film were given isoniazid coverage , however, later in the study, all patients were so treated" "general supportive care required in hepatic decompensation. Special attention was given to fluid and electrolyte balance , prompt treatment of hepatic encephalopathy and repeated evaluation for infection... most patients had daily estimation of the caloric and protein intake by a hospital dietitian... who were unable to take oral nutrition received parenterally a minimum of 400 calories per day as glucose Duration of treatment and of follow‐up: 45 days after randomisation
Outcomes	The trial outcomes were: Mortality Liver biochemistry Liver histology Adverse events
Notes	Country: USA Letter sent to study authors in March 2000. No answer received. "Twenty‐three patients were accepted for studying. However, three died within 36 hours of the start of the therapy and were excluded from analysis before the code was broken because they did not receive adequate medication." Supported in part by a gastroenterology‐research training grant (AM‐05099) from the National Institute of Artrithis and Metabolic Diseases (a portion of this work was conducted within the Clinical Research Center of the University of Washington, with support by a grant MO1 FR‐37 from the National Institutes of Health
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"... randomisation was achieved by a number drawn from a pool"
Allocation concealment (selection bias)	Low risk	"the case was randomised into one of the two treatment groups. Both the steroid (6‐ methyl prednisolone, or Medrol) and the placebo (lactose) were packaged and coded by number in both parenteral and oral forms (prepared and supplied through the courtesy of the Upjohn Co, Kalamazoo, Mich)..."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Neither patients nor physicians knew which form of treatment was used until the study had been completed, when the code was broken"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"At the conclusion of the study, all needle biopsy and post‐mortem liver specimens were coded and read in blind review by the same observer"
Incomplete outcome data (attrition bias) All outcomes	High risk	13% "Twenty three patients were accepted for study, three died within 36 hours of the start of therapy and were excluded from analysis before the code was broken because they didn't receive adequate medication. The final series thus consisted of 20 patients "
Selective reporting (reporting bias)	Low risk	All‐cause mortality, serious adverse events, and liver‐related mortality are reported.
For‐profit bias	Low risk	"The drugs were provided by Upjohn Co., Kalamazoo, Mich." Supported in part by a gastroenterology‐research training grant (AM‐05099) from the National Institute of Artrithis and Metabolic Diseases (a portion of this work was conducted within the Clinical Research Center of the University of Washington, with support by a grant MO1 FR‐37 from the National Institutes of Health
Other bias	Low risk	None suspected.