Korean J Intern Med.  2020 May;35(3):723-731. 10.3904/kjim.2018.407.

Liver enzyme elevation in patients with ankylosing spondylitis treated with tumor necrosis factor inhibitors: a single-center historical cohort study

• Choi SJ
• Oh JS
• Hong S
• Lee CK
• Yoo B
• Kim YG

• KMID: 2502063
• DOI: http://doi.org/10.3904/kjim.2018.407

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.

Keyword

Aspartate aminotransferases; Alanine transaminase; Spondylitis, ankylosing; Tumor necrosis factor-alpha