Abstract

Severe alcoholic hepatitis (SAH) is associated with significant morbidity and mortality, yet the treatment options available are very limited. Past studies have evaluated the efficacy of infliximab in such patients; however, they were limited by sample size. Our aim was to perform a systematic review of these studies to assess the role of infliximab in patients with SAH.We conducted a literature search using electronic database engines including Ovid, PubMed, Scopus, MEDLINE and Cochrane Library from inception to October 2018 to identify published articles addressing outcomes in patients treated for alcoholic hepatitis with infliximab. The primary outcome reviewed was one-month mortality. Secondary outcomes included rate and type of infection; cause of mortality; levels of aspartate aminotransferase, alanine aminotransferase, bilirubin and tumor necrosis factor-α; and Maddrey discriminant function.Five studies including two randomized controlled trials and three case series were included in our analysis with a total sample size of 70 patients. One-month mortality ranged from 10% to 17% in patients who received a single dose of infliximab with or without prednisone compared to 38% in patients who received three doses of infliximab in combination with prednisone. A single dose of infliximab was associated with an infection rate of 10% to 26% in contrast to an 89% rate with three doses of infliximab.Infliximab, when used in a single dose, could potentially be an alternative agent for the management of SAH in a large group of patients who have contraindications such as gastrointestinal bleeding, uncontrolled diabetes or an active hepatitis infection. It might also have a role in the prevention of hepatorenal syndrome. There is a need for larger trials to evaluate the role of infliximab in a cohort of patients who are not candidates for prednisolone therapy.

Highlights

  • BackgroundAlcoholic liver disease (ALD) encompasses a spectrum of pathologies, ranging from simple steatosis to frank cirrhosis

  • Alcoholic hepatitis (AH), a severe manifestation of And BackgroundAlcoholic liver disease (ALD) is caused by excessive alcohol use

  • Various proinflammatory cytokines have been implicated in the pathogenesis of AH including tumor necrosis factor-alpha (TNF-α), interleukin 1 and interleukin 8 (IL-1, IL-8) [4,5,6]

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Summary

Introduction

Alcoholic liver disease (ALD) encompasses a spectrum of pathologies, ranging from simple steatosis to frank cirrhosis. Alcoholic hepatitis (AH), a severe manifestation of ALD is caused by excessive alcohol use. The true prevalence of AH is unknown; it accounted for 0.8% of all hospitalizations in 2010 in the United States [1]. Despite the increasing prevalence and severity of AH, there are no consistent recommendations for its management. Severe alcoholic hepatitis (SAH) is defined by a Maddrey discriminant fraction (MDF) of >32 or model for end-stage liver disease (MELD) score of >20, which carries a 28-day mortality ranging from 30 to 50% [2,3]. Various proinflammatory cytokines have been implicated in the pathogenesis of AH including tumor necrosis factor-alpha (TNF-α), interleukin 1 and interleukin 8 (IL-1, IL-8) [4,5,6]

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