Background/Purpose: TNF inhibitors have been known to cause liver enzyme elevation in rheumatologic disease. However, liver enzyme elevation could be affected easily by other causes including concomitant medications and underlying liver disease. In ankylosing spondylitis (AS), there has been little analysis related to the study of liver enzyme elevation. The use of disease-modifying anti-rheumatic drugs (DMARDs) for treating AS has become less common after the introduction of TNF inhibitor treatment. Therefore, we identified the incidence and risk factors of liver enzyme elevation after TNF inhibitor exposure in patients with AS.

Methods: Retrospectively, we collected 363 AS patients who had normal liver enzyme levels before treatment with TNF inhibitor in a tertiary hospital from Jan. 2003 to Dec. 2017. Patients did not have evidence of viral or alcoholic liver disease before treatment with TNF inhibitor. TNF inhibitor medications included adalimumab, etanercept, infliximab, and golimumab. Clinical, laboratory and medication data were collected from the electronic medical records. Liver enzyme elevation was defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels >1x upper limit of normal (ULN) and consecutively elevated for two or more visits without evidence of new exposure to hepatotoxic drugs. The Cox proportional hazards model was used to evaluate hazard ratio (HR) with 95% confidence interval (CI) for liver enzyme elevation.

Results: The incidence of liver enzyme elevation was 23.7% (86/363). AST and/or ALT elevation >2× ULN occurred in 37.2% (32/86) of patients with liver enzyme elevation. The median duration of TNF inhibitor exposure before liver enzyme elevation was 3.72 months (IQR 1.77-12.51). There was no difference in the occurrence of liver enzyme elevation in the DMARDs and TNF inhibitor users compared with TNF inhibitor alone users (24.5% vs 22.9%, p=0.718). In multivariable analysis, the HRs for liver enzyme elevation were 3.41 (95% CI 1.44-8.06) for males, 3.02 (95% CI 1.68-5.43) for fatty liver disease, and 2.54 (95% CI 1.54-4.19) for hyperlipidemia. Among TNF inhibitors, infliximab was weakly associated with liver enzyme elevation compared with adalimumab, etanercept, and golimumab (HR=0.75, 95% CI 0.59-0.96). Among patients with liver enzyme elevation, 13 patients switched to another TNF inhibitor during the follow-up period. The normalization of the liver enzyme levels after switching was observed in four patients.

Conclusion: Liver enzyme elevation was observed in approximately a quarter of AS patients after treatment with TNF inhibitors. Male gender, fatty liver disease, and hyperlipidemia were independent risk factors for liver enzyme elevation. Switching to another TNF inhibitor had limited effect on normalization of the liver enzyme levels.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/liver-enzyme-elevation-in-patients-with-ankylosing-spondylitis-treated-with-tnf-inhibitor-a-single-center-historical-cohort-study/