[Autoimmune hepatitis induced by fibrates]

Abstract

Aim: Long term treatment by fibrates could induce chronic hepatitis associated with auto-antibodies. The aim of this study was to assess the features of this hepatitis.

Methods: Baseline clinical and biological features, and liver biopsy in 5 patients with fibrate-induced chronic hepatitis were studied, as well as their outcome.

Results: At enrollment, patients (4 men, mean age 65 years) had highly (n = 3) or mildly (n = 2) increased serum aminotransferase activity, hypergammaglobulinemia and high titers of anti-nuclear antibodies (with homogenous fluorescence in 3 cases). Liver biopsies demonstrated a lympho-plasmocytic infiltrate in all cases. Hepatocellular necrosis was multilobular in 2 cases, and mild to moderate, located in lobular and periportal areas in 3 cases. Cirrhosis was found at presentation in 3 cases and developed within a few months in the 2 other patients. After discontinuation of fibrates, aminotransferase activity normalized within 6 weeks either spontaneously (n = 3) or under immunosuppressive treatment (n = 2). Immunosuppression was rapidly withdrawn in 2 patients (< 18 months) without relapse, while one patient was treated for 4 years because of relapse after early withdrawal. A second liver biopsy performed 6 months after discontinuation of fibrates in an untreated-patient showed no inflammation or necrosis.

Conclusion: These observations suggest that fibrates could trigger chronic liver disease resembling type I auto-immune chronic hepatitis, which resolves after drug withdrawal.