Review
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World J Gastroenterol. Dec 14, 2014; 20(46): 17352-17359
Published online Dec 14, 2014. doi: 10.3748/wjg.v20.i46.17352
Anti-tumour necrosis factor agent and liver injury: Literature review, recommendations for management
Roberta Elisa Rossi, Ioanna Parisi, Edward John Despott, Andrew Kenneth Burroughs, James O'Beirne, Dario Conte, Mark Ian Hamilton, Charles Daniel Murray
Roberta Elisa Rossi, Edward John Despott, Mark Ian Hamilton, Charles Daniel Murray, Centre for Gastroenterology, Royal Free Hospital, London NW3 2QG, United Kingdom
Roberta Elisa Rossi, Dario Conte, Department of Pathophysiology and Organ Transplant, Universita’ degli Studi di Milano, 20122 Milano, Italy
Roberta Elisa Rossi, Dario Conte, Division of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milano, Italy
Ioanna Parisi, Andrew Kenneth Burroughs, James O'Beirne, Sheila Sherlock Liver Centre, Royal Free Hospital and Institute of Liver and Digestive Health, London NW3 2PF, United Kingdom
Author contributions: Rossi RE, Hamilton MI and Murray CD designed the research; Rossi RE and Parisi I performed the literature search and wrote the first draft of the paper; Despott EJ, Burroughs AK, O'Beirne J, Conte D, Hamilton MI and Murray CD reviewed for important intellectual content; Rossi RE wrote the final version of the paper; all the authors approved it.
Correspondence to: Roberta Elisa Rossi, MD, Centre for Gastroenterology, Royal Free Hospital, Pond Street, London NW3 2QG, United Kingdom. robertaelisa.rossi@gmail.com
Telephone: +44-20-78302867 Fax: +44-20-74726728
Received: February 14, 2014
Revised: April 14, 2014
Accepted: July 24, 2014
Published online: December 14, 2014
Processing time: 307 Days and 9.9 Hours
Abstract

Abnormalities in liver function tests, including transient and self-limiting hypertransaminasemia, cholestatic disease and hepatitis, can develop during treatment with anti-tumour-necrosis-factor (TNF) therapy. The optimal management of liver injury related to anti-TNF therapy is still a matter of debate. Although some authors recommend discontinuing treatment in case of both a rise of alanine aminotransferase more than 5 times the upper limit of normal, or the occurrence of jaundice, there are no standard guidelines for the management of anti-TNF-related liver injury. Bibliographical searches were performed in PubMed, using the following key words: inflammatory bowel disease (IBD); TNF inhibitors; hypertransaminasemia; drug-related liver injury; infliximab. According to published data, elevation of transaminases in patients with IBD treated with anti-TNF is a common finding, but resolution appears to be the usual outcome. Anti-TNF agents seem to be safe with a low risk of causing severe drug-related liver injury. According to our centre experience, we found that hypertransaminasemia was a common, mainly self-limiting finding in our IBD cohort and was not correlated to infliximab treatment on both univariate and multivariate analyses. An algorithm for the management of liver impairment occurring during anti-TNF treatment is also proposed and this highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision in case of severe rise of transaminases. However, hepatic injury is generally self-limiting and drug withdrawal seems to be an exception.

Keywords: Inflammatory bowel disease; Tumour necrosis factor inhibitors; Hypertransaminasemia; Drug-related liver injury; Infliximab

Core tip: Anti-tumour-necrosis-factor (TNF) agents appear to be safe with a low risk of causing severe liver injury. Standard guidelines for the management of anti-TNF-related liver injury are lacking. Our approach, based on evidence from literature and our centre experience, highlights the need of a multidisciplinary approach and suggests liver biopsy as a key-point in the management decision. We particularly highlight that continuation of the anti-TNF treatment is usually possible, in view of the rarity of severe liver injury and the lack of alternative medical options in case of severe active inflammatory bowel disease.