Abstract
Alcoholic liver disease (ALD) and its complications is still one of the most frequent causes of death in the Western world. Treatment modalities for both alcoholic steatohepatitis (ASH; the major inflammatory complication of ALD) and alcoholic liver cirrhosis are insufficient. Severe ASH is associated with a high mortality; although glucocorticoid treatment has been reported to improve survival, meta-analyses of clinical trials performed to date have failed to show a convincing benefit of such an approach. Most of the progress in understanding these diseases, especially ASH, has come from studies of cytokines. Various proinflammatory cytokines, such as tumor necrosis factor (TNF), have been proposed to have an important role in the pathophysiology of ALD and its complications. Pilot studies on the use of anti-TNF drugs, such as pentoxifylline or infliximab, in the treatment of ASH have now been performed with various levels of success. The treatment of patients with alcohol-related cirrhosis is mainly symptomatic and no therapies are currently available except orthotopic liver transplantation for end-stage liver disease. Independent of the stage of disease, abstinence from alcohol is the cornerstone of management. New treatment modalities for these diseases are eagerly awaited.
Key Points
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Severe alcoholic steatohepatitis (ASH) is the major complication of advanced alcoholic liver disease (ALD) and has a high mortality even when treated with corticosteroids
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Despite the importance of reactive oxygen species in the pathophysiology of ALD and ASH, antioxidants provide no benefit in the treatment of patients with ASH
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Proinflammatory cytokines are important in the pathophysiology of ASH and ALD and might mediate most of the inflammatory aspects of this disorder
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New treatment modalities for ASH might involve antagonism of proinflammatory cytokines such as tumor necrosis factor (TNF), by specific anti-TNF antibodies or other treatment strategies that specifically target TNF
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Propylthiouracil and S-adenosyl methionine might be beneficial for patients with alcoholic cirrhosis, but both agents need to undergo further randomized controlled trials before their use can be recommended
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Liver transplantation is an effective therapy for patients with advanced alcoholic cirrhosis who have failed to recover after a period of abstinence
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Acknowledgements
We gratefully acknowledge Dr Alexander Moschen, Innsbruck Medical University, for helpful discussions and critical reading of the manuscript. H Tilg is supported by a grant from the Austrian Science Foundation (P17447) and the Christian–Doppler Research Society.
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Tilg, H., Day, C. Management strategies in alcoholic liver disease. Nat Rev Gastroenterol Hepatol 4, 24–34 (2007). https://doi.org/10.1038/ncpgasthep0683
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DOI: https://doi.org/10.1038/ncpgasthep0683
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