END-STAGE LIVER-DISEASE DEVELOPING WITH THE USE OF METHOTREXATE IN HETEROZYGOUS ALPHA(1)-ANTITRYPSIN DEFICIENCY

We report a case of cirrhosis developing in a man who was heterozygous for alpha(1)-antitrypsin deficiency and who was receiving methotrexat e for severe rheumatoid arthritis. The alpha(1)-antitrypsin phenotype PiMZ has been associated with cryptogenic cirrhosis. Our patient had n o biochemical or histologic evidence of chronic liver disease during t he first year of receiving methotrexate. We postulate that the PiMZ st ate may result in enhanced susceptibility to methotrexate-induced hepa tic toxicity and should be screened for if liver function abnormalitie s occur during methotrexate therapy.