Liver Transplantation for Infliximab-Induced Fulminant Hepatic Failure

Abstract

Purpose: Infliximab (Remicade®) is a chimeric monoclonal antibody that binds TNFα and is indicated for Rheumatoid arthritis, Crohn's disease, Ankylosing spondylitis, Psoriatic arthritis, and Ulcerative colitis. Potential adverse effects of Infliximab include infusion reactions and risk of serious infections including tuberculosis. Hepatotoxicty has recently been recognized as a potentially serious adverse effect of Infliximab. We report a case of Infliximab-induced fulminant hepatic failure resulting in orthotopic liver transplantation. Methods: A 53 year old African-American female with Rheumatoid arthritis was initially treated with systemic steroids and methotrexate. She had no history of chronic liver disease and all baseline laboratory studies, including liver panel, were within normal limits. Since she continued to remain symptomatic, methotrexate was stopped and infliximab was initiated. She received four infusions over 12 weeks and presented two weeks after the fourth infusion with progressively worsening jaundice. Infliximab was then discontinued. Laboratory studies revealed: Total Bilirubin 4.3 mg/dl, AST 1797 U/L, ALT 1807 U/L, Alkaline phosphatase 193 U/L, PT/INR 15.3/1.6. Since her laboratory studies continued to worsen, a liver biopsy was performed. This revealed marked bile duct damage, diffuse ballooning degeneration of hepatocytes with lobular disarray and cholestasis with a scattered mixed inflammatory infiltrate. Over the course of the next several days, there was continued deterioration of hepatic synthetic function (Total Bilirubin 19.9, PT/INR 27.7/3.1) with onset of hepatic encephalopathy. She was then listed and underwent orthotopic liver transplantation ten weeks after the last infusion of infliximab. The explant showed submassive necrosis with large areas of hepatocyte dropout, collapse of hepatic lobules and marked bile ductular proliferation with cholestasis. She had an uneventful post-operative course and remains well six months after transplant. Conclusion: The precise mechanism of hepatotoxicity of TNFα inhibitors remains unclear. Unlike many of the reported cases of hepatotoxicity related to use of Infliximab, our patient was not on concomitant therapy with immunsuppresants or other potentially hepatotoxic medications. Our case highlights the potential for severe cholestatic liver injury from Infliximab. Clinicians should be aware of this possibility with prompt discontinuation of the drug in patients who develop progressive liver test abnormalities.