Volume 149, Issue 4, Pages 958-970.e12 (October 2015) Comparative Effectiveness of Pharmacological Interventions for Severe Alcoholic Hepatitis: A Systematic Review and Network Meta-analysis  Siddharth Singh, Mohammad Hassan Murad, Apoorva K. Chandar, Connie M. Bongiorno, Ashwani K. Singal, Stephen R. Atkinson, Mark R. Thursz, Rohit Loomba, Vijay H. Shah  Gastroenterology  Volume 149, Issue 4, Pages 958-970.e12 (October 2015) DOI: 10.1053/j.gastro.2015.06.006 Copyright © 2015 AGA Institute Terms and Conditions

Figure 1 Flow sheet summarizing study identification and selection. CS, corticosteroids; PTX, pentoxifylline; RCT, randomized controlled trial. Gastroenterology 2015 149, 958-970.e12DOI: (10.1053/j.gastro.2015.06.006) Copyright © 2015 AGA Institute Terms and Conditions

Figure 2 Evidence network of different pharmacological interventions for decreasing short-term mortality in patients with severe alcoholic hepatitis. The numbers (and numbers in parentheses) refer to the number of trials (and number of combined number of participants in these trials), and the thickness of the connecting line corresponds to the number of trials between comparators. Gastroenterology 2015 149, 958-970.e12DOI: (10.1053/j.gastro.2015.06.006) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 1 Quality assessment of included studies. (A) Overall and (B) study-level risk of bias, using Cochrane’s risk of bias assessment tool. In this tool, studies were deemed to be at high, low, or unclear risk of bias based on adequacy of sequence generation, allocation concealment, blinding, method of addressing incomplete data, selective reporting, and other biases. The review authors' judgments about each risk of bias item are presented as percentages across all included studies and for each included study. For mortality (which is highly unlikely to be influenced by performance bias or detection bias), open-label or single-blinded studies were not considered at high risk of bias, even if patients, physicians, and/or outcome assessors were not blinded, in accordance with the Cochrane handbook. Gastroenterology 2015 149, 958-970.e12DOI: (10.1053/j.gastro.2015.06.006) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 1 Quality assessment of included studies. (A) Overall and (B) study-level risk of bias, using Cochrane’s risk of bias assessment tool. In this tool, studies were deemed to be at high, low, or unclear risk of bias based on adequacy of sequence generation, allocation concealment, blinding, method of addressing incomplete data, selective reporting, and other biases. The review authors' judgments about each risk of bias item are presented as percentages across all included studies and for each included study. For mortality (which is highly unlikely to be influenced by performance bias or detection bias), open-label or single-blinded studies were not considered at high risk of bias, even if patients, physicians, and/or outcome assessors were not blinded, in accordance with the Cochrane handbook. Gastroenterology 2015 149, 958-970.e12DOI: (10.1053/j.gastro.2015.06.006) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 2 Direct meta-analysis of different pharmacological interventions for (A) decreasing short-term mortality (1 month), (B) medium-term mortality (3-12 months), (C) acute kidney injury and (D) infections in patients with severe alcoholic hepatitis. Please note that in the forest plot, ‘experimental’ refers to first treatment group, whereas “control” refers to the second treatment group. Gastroenterology 2015 149, 958-970.e12DOI: (10.1053/j.gastro.2015.06.006) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 2 Direct meta-analysis of different pharmacological interventions for (A) decreasing short-term mortality (1 month), (B) medium-term mortality (3-12 months), (C) acute kidney injury and (D) infections in patients with severe alcoholic hepatitis. Please note that in the forest plot, ‘experimental’ refers to first treatment group, whereas “control” refers to the second treatment group. Gastroenterology 2015 149, 958-970.e12DOI: (10.1053/j.gastro.2015.06.006) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 2 Direct meta-analysis of different pharmacological interventions for (A) decreasing short-term mortality (1 month), (B) medium-term mortality (3-12 months), (C) acute kidney injury and (D) infections in patients with severe alcoholic hepatitis. Please note that in the forest plot, ‘experimental’ refers to first treatment group, whereas “control” refers to the second treatment group. Gastroenterology 2015 149, 958-970.e12DOI: (10.1053/j.gastro.2015.06.006) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 2 Direct meta-analysis of different pharmacological interventions for (A) decreasing short-term mortality (1 month), (B) medium-term mortality (3-12 months), (C) acute kidney injury and (D) infections in patients with severe alcoholic hepatitis. Please note that in the forest plot, ‘experimental’ refers to first treatment group, whereas “control” refers to the second treatment group. Gastroenterology 2015 149, 958-970.e12DOI: (10.1053/j.gastro.2015.06.006) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 3 Ranking probabilities of treatment for severe alcoholic hepatitis, for short-term mortality. Gastroenterology 2015 149, 958-970.e12DOI: (10.1053/j.gastro.2015.06.006) Copyright © 2015 AGA Institute Terms and Conditions

Supplementary Figure 4 Funnel plot of trials of severe alcoholic hepatitis. There is no evidence of funnel plot asymmetry, arguing against significant publication bias. Gastroenterology 2015 149, 958-970.e12DOI: (10.1053/j.gastro.2015.06.006) Copyright © 2015 AGA Institute Terms and Conditions