INFLIXIMAB-INDUCED HEPATITIS

I Doucet, M Lemoyne, JP Villeneuve

Department of Medicine, Hôpital Saint-Luc du CHUM, Montreal, Quebec

INTRODUCTION: Infliximab is a novel therapy for Crohn's disease and rheumatoid arthritis. We report a case of hepatitis following infliximab.
CASE REPORT: A 47 year-old Caucasian woman had Sjogren syndrome and rheumatoid arthritis since 1993. In 1999 she was diagnosed with Crohn's disease. Her medication included hydroxy chloroquine, prednisone, methotrexate (15 mg weekly for the past 2 years) and Salofalk. In October 2001, infliximab (3.8 mg/kg) was initiated because of continuing joint pain. She received four monthly doses of infliximab from October 2001 to January 2002. Liver function tests were normal before initiating infliximab. After the 4th dose, she complained of progressive fatigue and epigastric pain. Physical exam was normal. Initial laboratory results were notable for elevated AST, ALT and alkaline phosphatase (117, 182 and 130 respectively). In February, these abnormalities persisted. (232, 315 and 150). The serum albumin level and INR were normal. There was a slight peripheral eosinophilia. She denied excessive alcohol use, exposure to toxins, or recent travel; she did not take any over the counter medication or natural products, and had no family history of liver disease. Laboratory tests did not show other causes of liver disease. A liver biopsy showed centrilobular necrosis with cholestasis, portal tract infiltrate with polymorphonuclear cells and eosinophilis, and cholangiolar proliferation. Infliximab was stopped, and the liver function tests normalized over the following 3 months.
DISCUSSION: There have been two previous reports of liver damage in association with infliximab. Menghini et al (Mayo Clin Proc 2002; 76:84) reported a case of cholestatic liver disease 19 days after 1st dose of infliximab in a Crohn's patient. The biopsy showed bland cholestasis without inflammation. The other case of hepatitis occurred after the 3rd dose of infliximab in a rheumatoid patient (Arthritis and Rheumatism 2001; 44:1966). In the present case, a re-challenge with infliximab to confirm the diagnosis was deemed dangerous, but causality assessment using the Naranjo and the Roussel-Uclaf probability scale indicated the infliximab was highly likely to be the cause of hepatitis. Thus, drug-induced hepato-toxicity should be considered in the differential diagnosis of patients with abnormal liver function tests, and receiving infliximab.