Einar S Björnsson1, Baldvin I Gunnarsson2, Gerdur Gröndal3, Jon G Jonasson4, Rannveig Einarsdottir3, Björn R Ludviksson5, Björn Gudbjörnsson6, Sigurdur Olafsson2. 1. Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Division of Gastroenterology and Hepatology, The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: einarsb@landspitali.is. 2. Division of Gastroenterology and Hepatology, The National University Hospital of Iceland, Reykjavik, Iceland. 3. Division of Rheumatology, The National University Hospital of Iceland, Reykjavik, Iceland. 4. Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Department of Pathology, The National University Hospital of Iceland, Reykjavik, Iceland. 5. Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Department of Immunology, The National University Hospital of Iceland, Reykjavik, Iceland. 6. Centre for Rheumatology Research, The National University Hospital of Iceland, Reykjavik, Iceland.
Abstract
BACKGROUND & AIMS: Antagonists of tumor necrosis factor (anti-TNF agents) can cause drug-induced liver injury (DILI), yet little is known about the level of risk. METHODS: 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). RESULTS: 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. CONCLUSIONS: Of anti-TNF agents, infliximab is associated most frequently with DILI, developing in 1 of 120 patients who received this drug. Fifty percent of patients with anti-TNF-associated DILI required steroid therapy, but most did not need long-term treatment. The addition of methotrexate to anti-TNF therapy might reduce the risk of DILI.
BACKGROUND & AIMS: Antagonists of tumor necrosis factor (anti-TNF agents) can cause drug-induced liver injury (DILI), yet little is known about the level of risk. METHODS: 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). RESULTS: 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. CONCLUSIONS: Of anti-TNF agents, infliximab is associated most frequently with DILI, developing in 1 of 120 patients who received this drug. Fifty percent of patients with anti-TNF-associated DILI required steroid therapy, but most did not need long-term treatment. The addition of methotrexate to anti-TNF therapy might reduce the risk of DILI.
Authors: Beverley Kok; Erica L W Lester; William M Lee; A James Hanje; R Todd Stravitz; Safwat Girgis; Vaishali Patel; Joshua R Peck; Christopher Esber; Constantine J Karvellas Journal: Dig Dis Sci Date: 2018-03-21 Impact factor: 3.199
Authors: Paola Nicoletti; Guruprasad P Aithal; Einar S Bjornsson; Raul J Andrade; Ashley Sawle; Marco Arrese; Huiman X Barnhart; Emmanuelle Bondon-Guitton; Paul H Hayashi; Fernando Bessone; Alfonso Carvajal; Ingolf Cascorbi; Elizabeth T Cirulli; Naga Chalasani; Anita Conforti; Sally A Coulthard; Mark J Daly; Christopher P Day; John F Dillon; Robert J Fontana; Jane I Grove; Pär Hallberg; Nelia Hernández; Luisa Ibáñez; Gerd A Kullak-Ublick; Tarja Laitinen; Dominique Larrey; M Isabel Lucena; Anke H Maitland-van der Zee; Jennifer H Martin; Mariam Molokhia; Munir Pirmohamed; Elizabeth E Powell; Shengying Qin; Jose Serrano; Camilla Stephens; Andrew Stolz; Mia Wadelius; Paul B Watkins; Aris Floratos; Yufeng Shen; Matthew R Nelson; Thomas J Urban; Ann K Daly Journal: Gastroenterology Date: 2016-12-30 Impact factor: 22.682
Authors: Muhammed Mustafa Alikhan; Emad Mansoor; Sagarika Satyavada; Katarina Greer; Wei Xin; Stanley Cohen; Gregory Cooper; Jeffry Katz Journal: ACG Case Rep J Date: 2021-05-14