Background/Purpose: Methotrexate (MTX) is a highly effective therapy for patients with rheumatologic and dermatologic conditions. Its use infers significant reduction in morbidity and mortality; however, it has been associated with a range of liver related adverse events. The risk with current dosing remains unknown. The American College of Rheumatology and American Association of Dermatology guidelines identify alcohol use, diabetes, and obesity as risk factors for MTX-induced liver injury.

Methods: We aim to quantify the prevalence of liver fibrosis and its relationship to clinical features. This will include total lifetime dose and parameters associated with non-alcoholic fatty liver disease (NAFLD) including obesity and diabetes. We predict those with NAFLD will be at increased risk of liver injury while taking MTX. A retrospective cross sectional study was performed among patients with rheumatoid arthritis or psoriasis/psoriatic arthritis who were referred to hepatology between 2015-2018 for evaluation of liver injury in the setting of chronic MTX use. The primary outcome was the prevalence of liver fibrosis using Fibroscan (≥6kPA = ≥F1 Fibrosis) or biopsy where available. Clinical predictive variables analyzed were demographics, co-morbidities, symptoms, physical exam findings, dose and duration of MTX use, laboratory values, and the controlled attenuation parameter (CAP) score, which is a method for measuring steatosis based on Fibroscan. Variables with a univariate P<0.2 were included in a multivariable logistic regression model.

Results: 30% (11/37) of patients had RA and 70 % (26/37) had psoriasis. 38% (14/37) were determined to have liver fibrosis. Rates were much higher among those with psoriasis (11/14 patients). Clinical variables retained in the final regression model were weight, body mass index (BMI), CAP score, and the presence of NAFLD.

Conclusion: Early detection of liver toxicity ensures improved outcomes and prevents unnecessary cessation of methotrexate. Those with NAFLD have an increased risk of methotrexate hepatotoxicity. We recommend individuals with risk factors for metabolic syndrome be referred to hepatology and screened for NAFLD prior to initiation of methotrexate.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-predictors-and-risk-of-methotrexate-induced-liver-fibrosis/