Noninvasive assessment of liver fibrosis in Crohn’s disease patients exposed to methotrexate

Abstract

Background: Methotrexate is widely used to treat some inflammatory chronic disorders, though it is hampered by the risk of liver fibrosis. Many recommendations have been made to assess methotrexate-related hepatotoxicity, including liver biopsy. However, other noninvasive methods to assess liver fibrosis have been developed and could be implemented for patients treated with methotrexate. Aim: The aim of the study was to compare the prevalence of liver fibrosis by means of noninvasive methods [aspartate transaminase-to-platelet ratio index (APRI) Forns index, and transient elastography] in patients with Crohn’s disease exposed or not to methotrexate, and to identify risk factors for liver fibrosis. Methods: Prospective, cross-sectional study. All patients with Crohn’s disease exposed to methotrexate were included and compared to an unselected cohort of outpatients with Crohn’s disease never exposed to methotrexate. Results: A total of 84 patients with Crohn’s disease, 56 exposed to methotrexate, and 28 controls, were included. Significant liver fibrosis was found in 7% of methotrexate-exposed patients with Crohn’s disease and 10% of controls as measured by transient elastography, and in 7% of controls as measured by the Forns index. No cases of liver fibrosis were detected by APRI. Only alcohol consumption, diabetes mellitus, and age were associated with significant liver fibrosis. Conclusions: Significant liver fibrosis is uncommon among patients with Crohn’s disease, even among those exposed to methotrexate. The risk of liver fibrosis in Crohn’s disease seems to depend on common risk factors for liver disease.

Review of existing evidence demonstrates that methotrexate does not cause liver fibrosis

“…Llaó et al carried out a case-control study in patients with Crohn's disease. 30 Fifty-six patients who were being treated with MTX versus 28 patients not treated with MTX were compared. Thirty-seven per cent were reported to be overweight, 5% with type 2 diabetes, and 13% with hyperlipidemia.…”

“…Llaó et al carried out a case–control study in patients with Crohn’s disease 30. Fifty-six patients who were being treated with MTX versus 28 patients not treated with MTX were compared.…”

Hepatobiliar manifestations in inflammatory bowel disease: A practical approach

“…This complication can occur acutely, with the development of acute liver failure, autoimmune hepatitis, and reactivation of hepatitis B, and a percentage of these patients may develop chronic damage[ 71 ]. Therapies with 5-aminosalicylates, as well as immunomodulators, can cause alterations in liver function tests, these have been widely described in the literature, they are summarized in Table 1 [ 72 - 78 ].…”