Singh 2018b.

Study characteristics
Methods	Prospective, open‐label, single‐centre, pilot randomised study
Participants	Country: India Period of recruitment: from October 2014 and March 2017 Number randomised: 57 Postrandomisation dropouts: 0 Revised sample size: 57 Average age: 45 Males: 100% Decompensated cirrhosis: 100% Acute‐on‐chronic liver failure: 100% Alcohol‐related cirrhosis: 100% Viral‐related cirrhosis: 0% Autoimmune disease‐related cirrhosis: 0% Other causes of cirrhosis: 0% Inclusion criteria Patients with severe AH admitted to the Liver Intensive Care Unit were eligible for inclusion in the study if they fulfilled the following criteria. 18 to 75 years of age Diagnosis of AH15 based on the following criteria: History of heavy alcohol use, mean intake, approximately 100 g/day) during the 3 months before enrolment Total serum bilirubin level > 5 mg/dL (86 mmol/L) Aspartate aminotransferase:alanine aminotransferase ratio > 2 and with an aspartate aminotransferase < 300 U/L Elevated prothrombin time (international normalised ratio) Leukocytosis Modified Maddrey’s discriminant function, calculated as 4.6 patient’s prothrombin time – control prothrombin time (in seconds) plus serum bilirubin level (mg/dL) of 32 Exclusion criteria Patients with any of the following were excluded. Hepatocellular carcinoma or portal vein thrombosis Refusal to participate in the study Prior treatment with glucocorticoids Significant medical comorbid conditions including hepatorenal syndrome (serum creatinine > 1.5 mg/dL), grade 3 or grade 4 hepatic encephalopathies, upper gastrointestinal bleeding within the preceding 10 days, uncontrolled bacterial infection, human immunodeficiency virus, hepatitis B virus, hepatitis C virus seropositivity, autoimmune hepatitis, haemochromatosis, Wilson’s disease, and alpha1‐antitrypsin deficiency Pregnancy Any previous known hypersensitivity to G‐CSF and NAC
Interventions	Experimental G‐CSF (Biocon, Bangalore, India) was given at a dose of 5 μg/kg subcutaneously every 12 hours for 5 consecutive days. NAC (Cipla Limited, Mumbai, India) was administered intravenously (day 1: n‐acetyl cysteine (NAC) at 150, 50, and 100 mg/kg in 250, 500, and 1000 mL of 5% glucose solution over 30 minutes, 4 hours, and 16 hours, respectively; days 2 to 5: 100 mg/kg/day in 1000 mL of 5% glucose solution). Control Standard medical treatment alone. All participants received standard medical therapy The standard medical treatment arm involved treatment with pentoxifylline (Sanofi Pharma, Mumbai, India) at a dose of 400 mg 3 times a day for 28 days and normal hospital nutrition (1800–2000 kcal/day). Diuretics, sodium restriction and albumin for the treatment of ascites, fresh frozen plasma for coagulopathy, and antibiotics for any focus of infection such as spontaneous bacterial peritonitis (SBP), pneumonia, cellulitis, and urinary tract infection were administered as indicated. All participants were admitted for at least 6 days following randomisation, and longer, if necessary, and were abstinent from alcohol throughout the study.
Outcomes	Primary outcome Survival at 90 days after inclusion in the study Secondary outcomes Number of CD34þ cells in the peripheral blood at day 6 Improvement in the clinical scores (MELD, Maddrey's discriminant function, CTP) at day 6 and 1, 2, and 3 months Adverse effects of G‐CSF and n‐acetyl cysteine
Notes	Conflicts of interest: the authors declare no conflicts. Funding: "The authors who have taken part in this study declare that partial funding was done for conducting this trial by the society for the study of liver diseases." ClincialTrials.gov number: NCT02971306
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	After obtaining informed written consent and confirming inclusion and exclusion criteria, participants were randomised to 1 of the 3 treatment groups. The randomisation was computer generated.
Allocation concealment (selection bias)	Low risk	The randomisation sequence was placed in opaque sequentially numbered envelopes.
Blinding of participants and personnel (performance bias) All outcomes	High risk	This was an open‐label study.
Blinding of outcome assessment (detection bias) overall mortality	Low risk	No information was given, but for the mortality outcome, low risk of bias.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information was given.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No participants were lost at follow up.
Selective reporting (reporting bias)	Unclear risk	The trial reported all‐cause mortality as a primary outcome.
Other bias	Unclear risk	We found no other bias.