End-stage liver disease developing with the use of methotrexate in heterozygous α₁-antitrypsin deficiency

We report a case of cirrhosis developing in a man who was heterozygous for α₁-antitrypsin deficiency and who was receiving methotrexate for severe rheumatoid arthritis. The α₁-antitrypsin phenotype PiMZ has been associated with cryptogenic cirrhosis. Our patient had no biochemical or histologic evidence of chronic liver disease during the first year of receiving methotrexate. We postulate that the PiMZ state may result in enhanced susceptibility to methotrexate-induced hepatic toxicity and should be screened for if liver function abnormalities occur during methotrexate therapy.