Comparative Effectiveness of Pharmacological Interventions for Severe Alcoholic Hepatitis: A Systematic Review and Network Meta-analysis

Siddharth Singh, Mohammad H Murad, Apoorva K. Chandar, Connie M. Bongiorno, Ashwani K. Singal, Stephen R. Atkinson, Mark R. Thursz, Rohit Loomba, Vijay Shah

Research output: Contribution to journalArticle

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Abstract

Background & Aims Severe alcoholic hepatitis (AH) has high mortality. We assessed the comparative effectiveness of pharmacological interventions for severe AH, through a network meta-analysis combining direct and indirect treatment comparisons. Methods We conducted a systematic literature review, through February 2015, for randomized controlled trials of adults with severe AH (discriminant function ≥32 and/or hepatic encephalopathy) that compared the efficacy of active pharmacologic interventions (corticosteroids, pentoxifylline, and N-acetylcysteine [NAC], alone or in combination) with each other or placebo, in reducing short-term mortality (primary outcome) and medium-term mortality, acute kidney injury, and/or infections (secondary outcomes). We performed direct and Bayesian network meta-analysis for all treatments, and used Grading of Recommendations Assessment, Development and Evaluation criteria to appraise quality of evidence. Results We included 22 randomized controlled trials (2621 patients) comparing 5 different interventions. In a direct meta-analysis, only corticosteroids decreased risk of short-term mortality. In a network meta-analysis, moderate quality evidence supported the use of corticosteroids alone (relative risk [RR], 0.54; 95% credible interval [CrI], 0.39-0.73) or in combination with pentoxifylline (RR, 0.53; 95% CrI, 0.36-0.78) or NAC (RR, 0.15; 95% CI, 0.05-0.39), to reduce short-term mortality; low quality evidence showed that pentoxifylline also decreased short-term mortality (RR, 0.70; 95% CrI, 0.50-0.97). The addition of NAC, but not pentoxifylline, to corticosteroids may be superior to corticosteroids alone for reducing short-term mortality. No treatment was effective in reducing medium-term mortality. Imprecise estimates and the small number of direct trials lowered the confidence in several comparisons. Conclusions In patients with severe AH, pentoxifylline and corticosteroids (alone and in combination with pentoxifylline or NAC) can reduce short-term mortality. No treatment decreases risk of medium-term mortality.

Original languageEnglish (US)
Article number59838
Pages (from-to)958-970
Number of pages13
JournalGastroenterology
Volume149
Issue number4
DOIs
StatePublished - Oct 1 2015

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Alcoholic Hepatitis
Pentoxifylline
Pharmacology
Mortality
Adrenal Cortex Hormones
Acetylcysteine
Randomized Controlled Trials
Network Meta-Analysis
Hepatic Encephalopathy
Therapeutics
Coinfection
Acute Kidney Injury
Meta-Analysis
Placebos

Keywords

  • Clinical Trial
  • GRADE
  • Liver Failure
  • Survival

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Comparative Effectiveness of Pharmacological Interventions for Severe Alcoholic Hepatitis : A Systematic Review and Network Meta-analysis. / Singh, Siddharth; Murad, Mohammad H; Chandar, Apoorva K.; Bongiorno, Connie M.; Singal, Ashwani K.; Atkinson, Stephen R.; Thursz, Mark R.; Loomba, Rohit; Shah, Vijay.

In: Gastroenterology, Vol. 149, No. 4, 59838, 01.10.2015, p. 958-970.

Research output: Contribution to journalArticle

Singh, Siddharth ; Murad, Mohammad H ; Chandar, Apoorva K. ; Bongiorno, Connie M. ; Singal, Ashwani K. ; Atkinson, Stephen R. ; Thursz, Mark R. ; Loomba, Rohit ; Shah, Vijay. / Comparative Effectiveness of Pharmacological Interventions for Severe Alcoholic Hepatitis : A Systematic Review and Network Meta-analysis. In: Gastroenterology. 2015 ; Vol. 149, No. 4. pp. 958-970.
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AU - Chandar, Apoorva K.

AU - Bongiorno, Connie M.

AU - Singal, Ashwani K.

AU - Atkinson, Stephen R.

AU - Thursz, Mark R.

AU - Loomba, Rohit

AU - Shah, Vijay

PY - 2015/10/1

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N2 - Background & Aims Severe alcoholic hepatitis (AH) has high mortality. We assessed the comparative effectiveness of pharmacological interventions for severe AH, through a network meta-analysis combining direct and indirect treatment comparisons. Methods We conducted a systematic literature review, through February 2015, for randomized controlled trials of adults with severe AH (discriminant function ≥32 and/or hepatic encephalopathy) that compared the efficacy of active pharmacologic interventions (corticosteroids, pentoxifylline, and N-acetylcysteine [NAC], alone or in combination) with each other or placebo, in reducing short-term mortality (primary outcome) and medium-term mortality, acute kidney injury, and/or infections (secondary outcomes). We performed direct and Bayesian network meta-analysis for all treatments, and used Grading of Recommendations Assessment, Development and Evaluation criteria to appraise quality of evidence. Results We included 22 randomized controlled trials (2621 patients) comparing 5 different interventions. In a direct meta-analysis, only corticosteroids decreased risk of short-term mortality. In a network meta-analysis, moderate quality evidence supported the use of corticosteroids alone (relative risk [RR], 0.54; 95% credible interval [CrI], 0.39-0.73) or in combination with pentoxifylline (RR, 0.53; 95% CrI, 0.36-0.78) or NAC (RR, 0.15; 95% CI, 0.05-0.39), to reduce short-term mortality; low quality evidence showed that pentoxifylline also decreased short-term mortality (RR, 0.70; 95% CrI, 0.50-0.97). The addition of NAC, but not pentoxifylline, to corticosteroids may be superior to corticosteroids alone for reducing short-term mortality. No treatment was effective in reducing medium-term mortality. Imprecise estimates and the small number of direct trials lowered the confidence in several comparisons. Conclusions In patients with severe AH, pentoxifylline and corticosteroids (alone and in combination with pentoxifylline or NAC) can reduce short-term mortality. No treatment decreases risk of medium-term mortality.

AB - Background & Aims Severe alcoholic hepatitis (AH) has high mortality. We assessed the comparative effectiveness of pharmacological interventions for severe AH, through a network meta-analysis combining direct and indirect treatment comparisons. Methods We conducted a systematic literature review, through February 2015, for randomized controlled trials of adults with severe AH (discriminant function ≥32 and/or hepatic encephalopathy) that compared the efficacy of active pharmacologic interventions (corticosteroids, pentoxifylline, and N-acetylcysteine [NAC], alone or in combination) with each other or placebo, in reducing short-term mortality (primary outcome) and medium-term mortality, acute kidney injury, and/or infections (secondary outcomes). We performed direct and Bayesian network meta-analysis for all treatments, and used Grading of Recommendations Assessment, Development and Evaluation criteria to appraise quality of evidence. Results We included 22 randomized controlled trials (2621 patients) comparing 5 different interventions. In a direct meta-analysis, only corticosteroids decreased risk of short-term mortality. In a network meta-analysis, moderate quality evidence supported the use of corticosteroids alone (relative risk [RR], 0.54; 95% credible interval [CrI], 0.39-0.73) or in combination with pentoxifylline (RR, 0.53; 95% CrI, 0.36-0.78) or NAC (RR, 0.15; 95% CI, 0.05-0.39), to reduce short-term mortality; low quality evidence showed that pentoxifylline also decreased short-term mortality (RR, 0.70; 95% CrI, 0.50-0.97). The addition of NAC, but not pentoxifylline, to corticosteroids may be superior to corticosteroids alone for reducing short-term mortality. No treatment was effective in reducing medium-term mortality. Imprecise estimates and the small number of direct trials lowered the confidence in several comparisons. Conclusions In patients with severe AH, pentoxifylline and corticosteroids (alone and in combination with pentoxifylline or NAC) can reduce short-term mortality. No treatment decreases risk of medium-term mortality.

KW - Clinical Trial

KW - GRADE

KW - Liver Failure

KW - Survival

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