Are Liver Biopsies Necessary in Psoriasis Patients Treated with Methotrexate?
Patients with certain risk factors had increased rates of fibrosis.
AAD guidelines encourage periodic liver biopsy to monitor psoriasis patients undergoing methotrexate therapy. Psoriasis patients frequently have features of the metabolic syndrome, including insulin resistance, type 2 diabetes mellitus, and obesity; obesity itself has been linked to hepatosteatosis, which can lead to fibrosis and cirrhosis. In these patients, factors associated with the greatest risk for liver toxicity are obesity, having hepatitis or diabetes mellitus, and overconsumption of alcohol. Many experts, however, have questioned the value of liver biopsy.
These authors retrospectively analyzed 71 patients who had undergone a total of 169 liver biopsies during methotrexate therapy for psoriasis (generally, biopsies were performed at every 1.5-g increase in the cumulative dose). The rate of fibrosis was high, but the rates of severe fibrosis and cirrhosis were low. The overall fibrosis rate was 71%, and it was significantly higher (96%) in patients with one or more of the identified risk factors (obesity, hepatitis, diabetes, and excessive alcohol intake). Only three patients developed cirrhosis, two of whom had normal liver biopsy results at therapy onset and then developed cirrhosis after 10 and 17 years. All 9 patients who overconsumed alcohol (>30 g daily) developed fibrosis, compared with 41 of the 62 patients (66%) who did not have this risk factor. All 7 patients with diabetes and 14 of the 15 overweight patients developed fibrosis. Abnormal liver enzyme levels were not associated with liver fibrosis.
An accompanying editorial suggests that although the mechanism of liver injury in the psoriatic population is unknown, multiple stresses on the hepatocyte (including, perhaps, elevated homocysteine levels; mutations of the methylene tetrahydrofolate reductase [MTHFR] gene [specifically the 677C to T polymorphism]; and external factors, such as diabetes, obesity, and alcohol intake) appear to contribute to the development of fibrosis.
Comment: There are several important points to learn about methotrexate use from these articles. First, it remains reasonable to get periodic liver biopsies in patients on methotrexate, but, in patients with no risk factors, these may reasonably be postponed until a cumulative dose of 3 to 4 grams is reached. Second, it would be wise to select patients carefully and avoid methotrexate for those with risk factors, when possible. Third, it might be reasonable to administer folic acid concomitantly with methotrexate, although folic acid may lessen its effectiveness. Fourth, the use of TNF antagonists might be beneficial for the liver, even with methotrexate therapy.
Jeffrey P. Callen, MD
Published in Journal Watch Dermatology June 15, 2007
Rosenberg P et al. Psoriasis patients with diabetes type 2 are at high risk of developing liver fibrosis during methotrexate treatment. J Hepatol 2007 Jun; 46:1111-8.
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Aithal GP. Dangerous liaisons: Drug, host and the environment. J Hepatol 2007 Jun; 46:995-8.
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