Methotrexate induced liver cirrhosis

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Abstract
SUMMARY: Seven hundred and sixty-four liver biopsies were performed in 328 psoriatics on treatment with methotrexate or being considered for systemic treatment either with methotrexate or with psoralens and long-wave ultraviolet light. The diagnosis of cirrhosis was established histologically in twenty-one patients. Two patients had cirrhosis in their premethotrexate biopsy and were not given methotrexate. The remainder all showed no signs of cirrhosis or fibrosis in their premethotrexate biopsy. The difference between the methotrexate treated psoriatics and the premethotrexate group was highly significant. Among thirty-nine patients treated for more than 5 years, ten developed cirrhosis (25.6%). Almost all patients were on a divided dose intermittent oral dosage schedule. The cumulative dose of methotrexate, when cirrhosis was first found, ranged from 590 to 8105 mg, with an average dosage of 2200 mg. Other factors contributing to cirrhosis in this study seem to be previous treatment with arsenic, a previous intake of alcohol, and lowered renal function. Data on later serial biopsies from fourteen patients, of which eleven continued to receive methotrexate due to very severe psoriasis, seem to indicate that methotrexate induced liver cirrhosis is not of a very aggressive nature. When evaluated blind no progression was found in most of the later biopsies, and a ‘cumulative cirrhosis index’ composed of the combined gradings for fibrosis, assessment of membrana limitans, fibrous destruction and regeneration showed a tendency to decrease. In three patients the latest of the serial biopsies showed no cirrhosis. The observation period on continued methotrexate therapy ranged from 1 to 7 years. None of the patients with cirrhosis differed from the remaining patients on methotrexate in their laboratory results for evaluating liver damage, and apart from transient increases in serum glutamic pyruvic transaminases no abnormalities were found. The data support the necessity of liver biopsies in the control of psoriatics treated with methotrexate. Liver biopsies should be performed at least in all psoriatics in whom a cumulative dosage of methotrexate exceeds 1.5g. The data also indicate that methotrexate can be continued at least for a while in patients where the indication is strong enough, if the dosage is maintained as low as possible and alcohol consumption avoided.