Fenofibrate-induced liver injury

摘要

Fenofibrate is a member of such fibrate class agents as bezafibrate and it work as a ligand of PPARα, and also shows a potent triglyceride-lowering effect. The elevation of aminotransferase levels has been frequently observed after the administration of fenofibrate and this phenomenon is considered to be non-pathological because fenofibrate activates the gene expression of the aminotransferases. Recently, fenofibrate has been used not only for hypercholesterolemia but also for primary biliary cirrhosis (PBC). However, the occurrence of liver injury induced by fenofibrate has not yet been reported written in the English literature. We herein report a rare case of liver injury due to the oral use of this drug. A 66-year-old Japanese female patient was admitted to undergo a further examination with a nearly 20-year history of liver dysfunction. She had been previously treated with 600 mg of ursodeoxycholic acid (UDCA) for nearly 6 mo at another clinic. On admission her conjunctiva was neither anemic nor icteric. The laboratory data revealed white blood cell counts of 6 600/μL with a differential of neutrophils 50%, lymphocyte 38%, monocytes 6%, basophils 1%, eosinophils 5%. The C reactive protein level was less than 0.3 mg/dL. The hepatic function profiles showed the total bilirubin to be 0.8 mg/dL, aspartate aminotransferase (AST) 40 IU/L, alanine aminotransferase (ALT) 29 IU/L, lactate dehydrogenase (LDH) 183 IU/L, alkaline phosphatase (ALP) 367 IU/L and gamma-glutamil transpeptidase (γ-GTP) 272 IU/L. Regarding the hepatitis virus, hepatitis B virus surface antigen and hepatitis C virus antibody were both negative. Serology revealed a high level of IgM of 393 mg/dL, and the antinuclear antibody of 80-fold and antimitochondrial antibody (AMA) of 320-fold each and antibody of 176 U/mL were positive for pyruvate dehydrogenase complex-E2. Histopathologically, a damaged bile duct with aggregates of lymphocytes with a nonsuppurative inflammatory destruction of the small bile duct and granuloma was seen in the portal area, which was compatible with those of Scheuer's stage 1 of primary biliary cirrhosis.