COMPARISON OF METHODS FOR IDENTIFYING EARLY METHOTREXATE-INDUCED HEPATOTOXICITY IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Hepatotoxicity may complicate therapy with methotrexate in patients wi th rheumatoid arthritis. Prevention of cirrhosis may depend upon early identification of liver damage, usually accomplished by serial biopsy . To determine the adequacy of noninvasive methods for identifying hep atotoxicity, 22 sets of data were obtained in patients undergoing ther apy with methotrexate for rheumatoid arthritis. Comparisons were made between liver biopsy, hepatocellular enzymes and two noninvasive radio isotopic methods that have been shown to be abnormal in hepatocellular disease: the rate constant of excretion of the C-14-aminopyrine and t he time from injection to peak hepatic activity of Tc-99m-diisopropyli midodiacetic acid. The hepatocellular enzymes and the time-to-peak-act ivity of diisopropyliminodiacetic acid were not useful predictors of m ethotrexate-induced hepatotoxicity. The aminopyrine breath test was ab normal in approximately half the patients with hepatotoxicity but show ed poor specificity. Noninvasive methods remain inferior to biopsy for the detection of mild to moderate methotrexate-induced hepatotoxicity in patients with rheumatoid arthritis.