Liver Toxicity in Rheumatoid Arthritis Patients Treated With Methotrexate

Background:Methotrexate (MTX) is one of the most commonly used disease-modifying antirheumatic drugs in the treatment of rheumatoid arthritis (RA) which can be associated with toxic effects on different organs. This study was designed to investigate the hepatotoxic effects in RA patients treated with MTX. Methods: In this cross-sectional observational study, RA patients who received standard dose regimen of methotrexate (7.5-15 mg/week) for a minimum of 3 months were included. Liver function parameters including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and albumin as well as prothrombin time (PT) were assessed for all patients. The patients were divided into two groups according to the MTX dose received: (1) low-dose group (≤ 7.5 mg/week) and (2) high-dose group (> 7.5 mg/week). Results:One-hundred patients (64% women) with mean age of 45.8 ± 7.5 years were studied. Eighty patients (80%) received low-dose MTX and the rest received high-dose MTX. Mean values of AST (P = 0.004), ALT (P = 0.001) and PT (P = 0.014) were significantly higher in patients receiving high-dose MTX compared with those who received low-dose MTX. Mean serum albumin was significantly lower in high-dose MTX receiving patients (P = 0.014). Moreover, elevated AST (RR (95% CI): 4.3 (2.1-8.7), P < 0.001), increased ALT (RR (95% CI): 4.9 (2.4-9.9), P < 0.001), and hypoalbuminemia (RR (95% CI): 2.3 (1.1-4.7), P = 0.030) were significantly more common in patients treated with high-dose MTX. The liver parameters restored to normal values after discontinuation of the treatment. Conclusion:MTX therapy especially in doses higher than 7.5 mg/week can be associated with increased risk for hepatotoxic effects. Regular monitoring for patients under MTX treatment is necessary.

Keywords:

Drug-Induced Liver Injury , Liver Function Tests , Methotrexate , Rheumatoid arthritis , Toxicity