A liver fibrosis cocktail? Psoriasis, methotrexate and genetic hemochromatosis

We describe our experience with two male psoriatic patients (A and B) on long term methotrexate therapy (cumulative dose A = 1.56 gms and B = 7.88 gms) with hetero- (A) and homozygous (B) genetic hemochromatosis. These patients liver function were monitored with routine biochemical profiling; apart from mild perivenular fibrosis in one patient (B), significant liver fibrosis was not identified in either patient with multiple interval percutaneous liver biopsies; in the latter instance this patient (B) had an additional risk factor of partiality to alcohol.We conclude that methotrexate therapy is relatively safe in patients with genetic hemochromatosis, with no other risk factor, but caution that the risk of fibrosis be monitored, preferably by non-invasive techniques, or by liver biopsy.Liver fibrosis, increased liver collagen content, [1-3] damage to the canals of Hering, [4] and cirrhosis, have been reported in patients being treated with methotrexate for psoriasis [5] or rheumatoid arthritis [6] but not in the context of inflammatory bowel disease;[7,8] some studies suggest that this risk of liver fibrosis is overstated [9-11]. The duration of methotrexate therapy,[12] patient age, weekly oral dosage schedule,[13] cumulative methotrexate dose,[14] risk factors for non-alcoholic steatohepatitis (obesity, diabetes mellitus, glucose intolerance)[6,15-17] and concurrent alcohol ingestion [14,18] have been identified as significant risk factors in the evolution of liver fibrosis in these patients. By contrast long-term low-dose methotrexate therapy, in the absence of excess alcohol ingestion or other profibrogenic agents or diseases, have been reported as being relatively free of the risk of developing fibrosis [19,20]. It has been recommended that baseline pre-treatment liver biopsies are necessary to define the initial histologic status of the liver [21,22]. Although annual, or other suitable interval, liver biopsies are recommended with this treatment, to monitor d