Liver enzyme elevation in patients with ankylosing spondylitis treated with tumor necrosis factor inhibitors: a single-center historical cohort study
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Background/Aims: Tumor necrosis factor inhibitors (TNFi) have been known to induce liver enzyme elevation, sometimes associated with viral reactivation or toxic hepatitis. We evaluated the incidence and risk factors of TNFi-associated liver enzyme elevation in Korean ankylosing spondylitis (AS) patients who previously had normal liver enzymes. Methods: Retrospectively, we collected data from the records of 363 AS patients treated with TNFi at a tertiary hospital from 2003 to 2017. Liver enzyme elevation was defined as abnormal elevation of aspartate aminotransferase and/or alanine aminotransferase levels on two or more consecutive visits. Patients with previously diagnosed liver disease were excluded. Results: The incidence of liver enzyme elevation was 23.7% (occurring in 86 of 363 patients). The median duration of TNFi exposure before liver enzyme elevation was 3.72 months (interquartile range, 1.77 to 12.51). There was no difference in the occurrence of liver enzyme elevation with concomitant disease-modifying anti-rheumatic drugs and TNFi compared to TNFi alone (23.9% vs. 23.6%). In multivariate analysis, the hazard ratios for liver enzyme elevation were 4.62 (95% confidence interval [CI], 1.43 to 15.01) for male sex, 4.06 (95% CI, 2.11 to 7.84) for underlying non-alcoholic fatty liver disease, and 2.53 (95% CI, 1.38 to 4.64) for hyperlipidemia. After switching to another TNFi, the liver enzyme elevation was not normalized in nine of 13 patients. Conclusions: Liver enzyme elevation was observed in a quarter of patients with AS receiving a TNFi. Male sex, non-alcoholic fatty liver disease, and hyperlipidemia were independent risk factors for liver enzyme elevation. Switching to another TNFi had a limited effect on restoring normal liver enzyme levels.
Abstract
Background/Aims: Tumor necrosis factor inhibitors (TNFi) have been known to induce liver enzyme elevation, sometimes associated with viral reactivation or toxic hepatitis. We evaluated the incidence and risk factors of TNFi-associated liver enzyme elevation in Korean ankylosing spondylitis (AS) patients who previously had normal liver enzymes. Methods: Retrospectively, we collected data from the records of 363 AS patients treated with TNFi at a tertiary hospital from 2003 to 2017. Liver enzyme elevation was defined as abnormal elevation of aspartate aminotransferase and/or alanine aminotransferase levels on two or more consecutive visits. Patients with previously diagnosed liver disease were excluded. Results: The incidence of liver enzyme elevation was 23.7% (occurring in 86 of 363 patients). The median duration of TNFi exposure before liver enzyme elevation was 3.72 months (interquartile range, 1.77 to 12.51). There was no difference in the occurrence of liver enzyme elevation with concomitant disease-modifying anti-rheumatic drugs and TNFi compared to TNFi alone (23.9% vs. 23.6%). In multivariate analysis, the hazard ratios for liver enzyme elevation were 4.62 (95% confidence interval [CI], 1.43 to 15.01) for male sex, 4.06 (95% CI, 2.11 to 7.84) for underlying non-alcoholic fatty liver disease, and 2.53 (95% CI, 1.38 to 4.64) for hyperlipidemia. After switching to another TNFi, the liver enzyme elevation was not normalized in nine of 13 patients. Conclusions: Liver enzyme elevation was observed in a quarter of patients with AS receiving a TNFi. Male sex, non-alcoholic fatty liver disease, and hyperlipidemia were independent risk factors for liver enzyme elevation. Switching to another TNFi had a limited effect on restoring normal liver enzyme levels.
참고문헌 (32)
- van der Heijde D, "2016 Update of the ASAS-EULAR management recommendations for axial spondyloarthritis", Ann Rheum Dis, 76, pp.978~991 (2017)
- Scheinfeld N, "A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept, infliximab and adalimumab", J Dermatolog Treat, 15, pp.280~294 (2004)
- van der Heijde D, "Efficacy and safety of adalimumab in patients with ankylosing spondylitis : results of a multicenter, randomized, double-blind, placebo-controlled trial", Arthritis Rheum, 54, pp.2136~2146 (2006)
- "Safety alerts for drugs, biologics medical devices, and dietary supplements. Remicade (Infliximab)" (2004)[URL]
- Parekh R, "Liver injury secondary to anti-TNF-alpha therapy in inflammatory bowel disease : a case series and review of the literature", Case Rep Gastrointest Med, 2014, pp.956463~ (2014)
- Tobon GJ, "Serious liver disease induced by infliximab", Clin Rheumatol, 26, pp.578~581 (2007)
- Ghabril M, "Liver injury from tumor necrosis factor-α antagonists : analysis of thirty-four cases", Clin Gastroenterol Hepatol, 11, pp.558~564 (2013)
- van Denderen JC, "Elevated liver enzymes in patients with ankylosing spondylitis treated with etanercept", Clin Rheumatol, 31, pp.1677~1682 (2012)
- Cansu DU, "Short-term course of chronic hepatitis B and C under treatment with etanercept associated with different disease modifying antirheumatic drugs without antiviral prophylaxis", J Rheumatol, 35, pp.421~424 (2008)
- Rodrigues S, "Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy : a single center report of 8 cases", World J Gastroenterol, 21, pp.7584~7588 (2015)
- Sokolove J, "Risk of elevated liver enzymes associated with TNF inhibitor utilisation in patients with rheumatoid arthritis", Ann Rheum Dis, 69, pp.1612~1617 (2010)
- Shelton E, "New onset idiosyncratic liver enzyme elevations with biological therapy in inflammatory bowel disease", Aliment Pharmacol Ther, 41, pp.972~979 (2015)
- Capkin E, "Treatment of ankylosing spondylitis with TNF inhibitors does not have adverse effect on results of liver function tests : a longitudinal study", Int J Rheum Dis, 18, pp.548~552 (2015)
- Goie The HS, "Evaluation of diagnostic criteria for ankylosing spondylitis : a comparison of the Rome, New York and modified New York criteria in patients with a positive clinical history screening test for ankylosing spondylitis", Br J Rheumatol, 24, pp.242~249 (1985)
- Korean Association for the Study of the Liver, "KASL clinical practice guidelines: management of alcoholic liver disease", Clin Mol Hepatol, 19, pp.216~254 (2013)
- Bjornsson ES, "Risk of drug-induced liver injury from tumor necrosis factor antagonists", Clin Gastroenterol Hepatol, 13, pp.602~608 (2015)
- Maini R, "Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group", Lancet, 354, pp.1932~1939 (1999)
- Tarantino G, "A prospective study of acute drug-induced liver injury in patients suffering from non-alcoholic fatty liver disease", Hepatol Res, 37, pp.410~415 (2007)
- Feagins LA, "Nonalcoholic fatty liver disease : a potential consequence of tumor necrosis factor-inhibitor therapy", Eur J Gastroenterol Hepatol, 27, pp.1154~1160 (2015)
- McGowan CE, "Changing shape of disease : nonalcoholic fatty liver disease in Crohn’s disease-a case series and review of the literature", Inflamm Bowel Dis, 18, pp.49~54 (2012)
- Sourianarayanane A, "Risk factors of non-alcoholic fatty liver disease in patients with inflammatory bowel disease", J Crohns Colitis, 7, pp.e279~ (2013)
- Sartini A, "Letter : TNFα inhibitors and prevalence of fatty liver disease in chronic inflammatory diseases", Aliment Pharmacol Ther, 42, pp.489~ (2015)
- Amacher DE, "Female gender as a susceptibility factor for drug-induced liver injury", Hum Exp Toxicol, 33, pp.928~939 (2014)
- Chalasani N, "Risk factors for idiosyncratic drug-induced liver injury", Gastroenterology, 138, pp.2246~2259 (2010)
- Soldin OP, "Sex differences in pharmacokinetics and pharmacodynamics", Clin Pharmacokinet, 48, pp.143~157 (2009)
- Gonnet-Gracia C, "Anti-nuclear antibodies, anti-DNA and C4 complement evolution in rheumatoid arthritis and ankylosing spondylitis treated with TNF-alpha blockers", Clin Exp Rheumatol, 26, pp.401~407 (2008)
- de Vries HS, "Appropriate infliximab infusion dosage and monitoring : results of a panel meeting of rheumatologists, dermatologists and gastroenterologists", Br J Clin Pharmacol, 71, pp.7~19 (2011)
- Garcia Aparicio AM, "Successful treatment with etanercept in a patient with hepatotoxicity closely related to infliximab", Clin Rheumatol, 26, pp.811~813 (2007)
- Massarotti M, "Successful treatment with etanercept of a patient with psoriatic arthritis after adalimumab-related hepatotoxicity", Int J Immunopathol Pharmacol, 22, pp.547~549 (2009)
- Cravo M, "Autoimmune hepatitis induced by infliximab in a patient with Crohn’s disease with no relapse after switching to adalimumab", BioDrugs, 24(Suppl 1), pp.25~27 (2010)
- Kooloos WM, "Potential role of pharmacogenetics in anti-TNF treatment of rheumatoid arthritis and Crohn’s disease", Drug Discov Today, 12, pp.125~131 (2007)
- Diehl AM, "Cytokine regulation of liver injury and repair", Immunol Rev, 174, pp.160~171 (2000)