S5772 Methotrexate-Induced Decompensated Liver Cirrhosis: A Case Report

Introduction: Methotrexate is a widely used medication for inflammatory conditions like rheumatoid arthritis with reversible liver toxicity as its most common side effect. Although well tolerated, rarely it can cause irreversible liver fibrosis and cirrhosis. We describe a case of methotrexate-induced decompensated liver cirrhosis in a patient with 20 years of methotrexate use. Case Description/Methods: A 76-year-old woman with a 20-year chronic history of rheumatoid arthritis managed with methotrexate presented with unresolving diarrhea, new onset bilateral lower extremity edema and mild abdominal distention. She was initially treated for suspected C. difficile infection with antibiotics and fidaxomicin. Initial imaging workup including bilateral lower extremity. Dopplers were negative for deep vein thrombosis, echo was unremarkable for any cardiac dysfunction. Her computed tomography of the abdomen revealed cirrhosis with mild to moderate ascites. A Doppler ultrasound showed patent hepatic vasculature without evidence of portal vein thrombosis or other obstructive causes. Prior comparison of the abdomen pelvis a year ago did not show significant evidence of cirrhosis. Chronic liver disease workup, including viral hepatitis panels (A, B, C), autoimmune markers such as P-ANCA, C-ANCA, antimitochondrial antibodies, and anti-smooth muscle antibodies, iron studies, and ceruloplasmin levels, was negative. The patient was started on diuretics (spironolactone and furosemide), resulting in partial improvement of ascites. She later required large-volume paracentesis due to worsening ascites and was diagnosed with hepatorenal syndrome (HRS), necessitating specialized treatment. Methotrexate was discontinued during her hospitalization. Discussion: CLD with evidence clinically decompensated liver cirrhosis significantly decreases the 5 years survival rate and further deterioration. Although non-alcoholic fatty liver disease and chronic alcohol use contribute to the major disease burden of cirrhosis, literature has reported uncommon cirrhosis associated with chronic use of methotrexate for rheumatoid arthritis. This case underscores the importance of regular monitoring in patients on long-term methotrexate therapy. Liver function tests and imaging should be performed periodically to detect early signs of hepatic dysfunction. Methotrexate cessation should be considered in patients with progressive liver damage to prevent irreversible fibrosis as they are at high risk due to dysregulation of innate immunity and increased pro-inflammatory cytokine production.