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World J Gastroenterol. Oct 21, 2012; 18(39): 5504-5513
Published online Oct 21, 2012. doi: 10.3748/wjg.v18.i39.5504
Molecular targets in the treatment of alcoholic hepatitis
Ashwin D Dhanda, Richard WL Lee, Peter L Collins, C Anne McCune
Ashwin D Dhanda, Peter L Collins, C Anne McCune, Department of Liver Medicine, University Hospitals Bristol NHS Foundation Trust, BS2 8HW Bristol, United Kingdom
Ashwin D Dhanda, Richard WL Lee, Department of Cellular and Molecular Medicine, School of Clinical Sciences, University of Bristol, BS9 1TD Bristol, United Kingdom
Author contributions: Dhanda AD wrote the initial draft; Lee RWL, Collins PL and McCune CA reviewed and edited the manuscript.
Correspondence to: Dr. C Anne McCune, MD, FRCP, Consultant Hepatologist, Department of Liver Medicine, University Hospitals Bristol NHS Foundation Trust, Bristol Royal Infirmary, Marlborough Street, BS2 8HW Bristol, United Kingdom. anne.mccune@uhbristol.nhs.uk
Telephone: +44-117-3422432 Fax: +44-117-3423533
Received: May 4, 2012
Revised: July 26, 2012
Accepted: July 29, 2012
Published online: October 21, 2012
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.

Keywords: Alcoholic hepatitis; Tumour necrosis factor-α; Pentoxifylline; Interleukins; Chemokine receptors