Risk of Drug-Induced Liver Injury From Tumor Necrosis Factor Antagonists.

• Published in: Clinical Gastroenterology and Hepatology
• Main Authors: Björnsson, Einar S, Gunnarsson, Baldvin I, Gröndal, Gerdur, Jonasson, Jon G, Einarsdottir, Rannveig, Ludviksson, Björn R, Gudbjörnsson, Björn, Olafsson, Sigurdur
• Other Authors: 1Faculty of Medicine, University of Iceland, Reykjavik; Division of Gastroenterology and Hepatology, The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: [e-mail]. 2Division of Gastroenterology and Hepatology, The National University Hospital of Iceland, Reykjavik, Iceland. 3Division of Rheumatology, The National University Hospital of Iceland, Reykjavik, Iceland. 4Faculty of Medicine, University of Iceland, Reykjavik; Department of Pathology, The National University Hospital of Iceland, Reykjavik, Iceland. 5Faculty of Medicine, University of Iceland, Reykjavik; Department of Immunology, The National University Hospital of Iceland, Reykjavik, Iceland. 6Centre for Rheumatology Research, The National University Hospital of Iceland, Reykjavik, Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Elsevier 2015
• Subjects: Lifrarbólga; Lifrarsjúkdómar; Hepatitis; Autoimmune; Liver Diseases; Tumor Necrosis Factor-alpha; Antibodies; Antinuclear; Iceland
• Online Access: http://hdl.handle.net/2336/338575; https://doi.org/10.1016/j.cgh.2014.07.062

To access publisher's full text version of this article click on the hyperlink at the bottom of the page Antagonists of tumor necrosis factor (anti-TNF agents) can cause drug-induced liver injury (DILI), yet little is known about the level of risk. We identified cases of DILI caused by anti-TNF agents in Iceland, from 2009 through 2013, at the National University Hospital of Iceland (n = 11). We collected data on the total use of the drugs by patients with DILI, and outcomes, compared with patients who received anti-TNF agents but who did not develop DILI (controls, n = 22). Of the 11 cases of DILI identified (8 women; mean age, 46 y), 9 cases were caused by infliximab. DILI developed in 1 of 120 patients who received infliximab, 1 in 270 patients who received adalimumab, and 1 in 430 patients who received etanercept. Most patients with infliximab-associated DILI developed this disorder after 4 infusions (n = 6). Four patients had jaundice at diagnosis of DILI, and 8 patients had hepatocellular liver injury. The mean peak level of alanine aminotransferase was 704 U/L, of aspartate aminotransferase was 503 U/L, of alkaline phosphatase was 261 U/L, and of bilirubin was 47 μmol/L. Seven patients with DILI were tested for antinuclear antibodies before therapy with an anti-TNF agent and 3 had positive test results, compared with 5 of the 14 controls tested. At DILI diagnosis, 8 of 11 patients tested positive for antinuclear antibodies. Of liver biopsy specimens collected from 5 patients with DILI, 3 showed signs of severe acute hepatitis. Only 9% of the patients who developed DILI received methotrexate during anti-TNF therapy, compared with 59% of controls (P = .009). DILI was treated with steroids in 5 patients, and in 4 cases steroid therapy was discontinued without relapse. Eight patients with DILI went on to receive treatment with different TNF antagonists without developing DILI. Of anti-TNF agents, infliximab is associated most frequently with DILI, developing in 1 of 120 patients who received this ...