Molecular targets in the treatment of alcoholic hepatitis

Ashwin D. Dhanda, Richard W. L. Lee, Peter L. Collins, C. Anne McCune*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

16 Citations (Scopus)

Abstract

Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflammatory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease. (C) 2012 Baishideng. All rights reserved.

Original languageEnglish
Pages (from-to)5504-5513
Number of pages10
JournalWorld Journal of Gastroenterology
Volume18
Issue number39
DOIs
Publication statusPublished - 21 Oct 2012

Keywords

  • RECOMBINANT HUMAN INTERLEUKIN-10
  • Interleukins
  • INDUCED LIVER-INJURY
  • Chemokine receptors
  • PLACEBO-CONTROLLED TRIAL
  • Pentoxifylline
  • REGULATORY T-CELLS
  • SHORT-TERM SURVIVAL
  • TUMOR-NECROSIS-FACTOR
  • VASCULAR ADHESION PROTEIN-1
  • RANDOMIZED CONTROLLED-TRIAL
  • Tumour necrosis factor-alpha
  • Alcoholic hepatitis
  • HEPATOCYTE GROWTH-FACTOR
  • ACTIVE CROHNS-DISEASE

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