Methotrexate-associated nonalcoholic fatty liver disease with transaminitis in rheumatoid arthritis.

Rajalingham Sakthiswary,Khai Pang Leong,Bernard Yu Hor Thong,Ee Tzun Koh,Grace Yin Lai Chan

doi:10.1155/2014/823763

Rajalingham Sakthiswary, Khai Pang Leong + Show 3 more

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https://doi.org/10.1155/2014/823763

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Journal: TheScientificWorldJournal	Publication Date: Jan 1, 2014
Citations: 51	License type: CC BY 3.0

Affiliation: Tan Tock Seng Hospital

Abstract

Background. The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore. Methods. Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis. Results. Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512). Conclusion. The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.

Highlights

Methotrexate (MTX) is recommended as the first-line disease-modifying antirheumatic drug (DMARD) by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) [1, 2] in the treatment of rheumatoid arthritis (RA)
To the best of our knowledge, this is the first study describing the predictors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in RA
In this large cohort of patients, the prevalence of the above condition was 4.7%. This figure is somewhat lower than expected as the reported prevalence of NAFLD in large population-based studies ranges from 11% to 24% [16, 17]

Summary

Introduction

Methotrexate (MTX) is recommended as the first-line disease-modifying antirheumatic drug (DMARD) by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) [1, 2] in the treatment of rheumatoid arthritis (RA). Nonalcoholic fatty liver disease (NAFLD), which refers to demonstration of hepatic steatosis by imaging or biopsy in the absence of heavy alcohol consumption [8], has been associated with MTX therapy [9, 10]. Liver biopsy specimens from RA patients have demonstrated hepatic folate deficiency and accumulation of MTX-polyglutamates [12]. The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore. Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis. The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis

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Conclusion