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Abstract

Background: Methotrexate (MTX) is a cornerstone drug in the management of rheumatoid arthritis (RA), but its use is associated with potential adverse effects, notably hepatotoxicity. Identifying the frequency and contributing factors to MTX-induced liver toxicity is essential for optimizing therapeutic safety in RA patients. Objective: To evaluate the frequency and associated risk factors of methotrexate-induced hepatotoxicity among patients with rheumatoid arthritis. Study Design: Descriptive cross-sectional study. Setting: This study was conducted at the Department of Medicine at Lady Reading Hospital, Peshawar. Duration of Study: The study was conducted over six months [11-September-2024 to 11-March-2025]. Methods: A total of 78 patients diagnosed with RA and undergoing MTX therapy, irrespective of age and gender, were enrolled. Hepatotoxicity was defined as serum alanine aminotransferase (ALT) levels exceeding twice the standard upper limit. Data regarding age, gender, MTX dosage, and liver function tests were recorded. Statistical analysis was performed using SPSS version 24. Chi-square and t-tests were used to assess associations, with a p-value ≤ 0.05 considered statistically significant. Results: The mean age of participants was 45.29 ± 12.38 years. Most were female (56.4%), while males accounted for 43.6%. Hepatotoxicity was observed in 19.2% of patients. A significant association was found between hepatotoxicity and higher MTX dosage (25 mg/week) (p = 0.01). No significant correlations were identified with age (p = 0.39) or gender (p = 0.39). Conclusion: Methotrexate-induced hepatotoxicity was found in nearly one-fifth of RA patients, with higher MTX doses significantly associated with liver enzyme elevation. These findings highlight the importance of regular liver function monitoring, particularly in patients receiving higher MTX dosages.