Current trials and novel therapeutic targets for alcoholic hepatitis

J Hepatol. 2019 Feb;70(2):305-313. doi: 10.1016/j.jhep.2018.10.026.

Abstract

Alcoholic hepatitis is a clinical syndrome in which patients present with acute-on-chronic liver failure and a high risk of short-term mortality. The current treatment of alcoholic hepatitis is suboptimal. Results recently published from the STOPAH study have improved our understanding of how best to design clinical trials for this condition. Although emerging data on liver transplantation for patients with alcoholic hepatitis are encouraging, less than 2% of these patients qualify. Clearly, there is an unmet need for novel treatments to improve the survival of these patients. Changes in the gut microbiota, inflammatory and cytokine signalling, oxidative stress and mitochondrial dysfunction, and abnormalities in the hepatic regenerative capacity alone or in combination contribute to the pathology of alcoholic hepatitis. In this chapter, we will describe the novel therapeutic agents targeting various pathways in the pathophysiology of alcoholic hepatitis. Specifically, we will describe the ongoing clinical trials in which some of these agents are being studied.

Keywords: ALD; Corticosteroids; STOPAH, Therapeutic.

Publication types

  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / therapeutic use
  • Clinical Trials as Topic
  • Drug Therapy, Combination
  • Ethanol / pharmacology
  • Fecal Microbiota Transplantation
  • Gastrointestinal Agents / therapeutic use
  • Gastrointestinal Microbiome / drug effects
  • Hepatitis, Alcoholic / drug therapy*
  • Hepatitis, Alcoholic / physiopathology*
  • Humans
  • Tumor Necrosis Factor Inhibitors / therapeutic use
  • Zinc / therapeutic use

Substances

  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents
  • Antioxidants
  • Gastrointestinal Agents
  • Tumor Necrosis Factor Inhibitors
  • Ethanol
  • Zinc