Presentation and Outcomes with Clinically Apparent Interferon Beta Hepatotoxicity

• Published in: Digestive diseases and sciences 2013-06, Vol.58 (6), p.1766-1775
• Main Authors: Fontana, Robert J., Hayashi, Paul, Bonkovsky, Herbert L., Kleiner, David E., Kochhar, Sweta, Gu, Jiezhun, Ghabril, Marwan
• Format: Article
• Language: English
• Subjects: Adult; Adverse Drug Reaction Reporting Systems; Autoantibodies; Autoimmunity; Biochemistry; Biological response modifiers; Chemical and Drug Induced Liver Injury - diagnosis; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - mortality; Female; Follow-Up Studies; Gastroenterology; Hepatology; Histology; Humans; Immunologic Factors - adverse effects; Immunologic Factors - therapeutic use; Interferon; Interferon beta; Interferon-beta - adverse effects; Interferon-beta - therapeutic use; Liver; Liver diseases; Medicine; Medicine & Public Health; Middle Aged; Multiple sclerosis; Multiple Sclerosis - complications; Multiple Sclerosis - drug therapy; Oncology; Original Article; Patient outcomes; Patients; Prognosis; Prospective Studies; Registries; Risk Factors; Transplant Surgery; Transplantation of organs, tissues, etc
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-012-2553-1

Aims The aim of this study was to describe the presenting features and outcomes of consecutive patients with liver injury attributed to interferon beta. Methods The presenting features of eight subjects with clinically apparent liver injury attributed to interferon beta enrolled in the U.S. Drug-Induced Liver Injury Network (DILIN) prospective registry between 2004 and 2010 were reviewed and compared to 11 published reports of symptomatic hepatotoxicity. Results All eight of the DILIN patients were women, 75 % were Caucasian and the mean age was 49 years. Most subjects presented with an acute hepatocellular injury pattern and mean serum alanine aminotransferase (ALT) levels were 725 ± 593 U/L. The median duration of interferon beta use before injury onset was 462 days, and four patients had been treated for more than a year. No patient had detectable antinuclear or smooth muscle antibodies. One patient died of acute liver failure and the remaining patients usually recovered within 2–3 months. Causality assessment scored three cases as definite, three highly likely, one probable and one possible. Eleven additional published cases were all women, mean age was 40 years, mean ALT at onset 840 U/L, and 7 (63 %) had autoantibodies. Liver histology in three cases from DILIN and nine from the literature commented upon centrilobular (zone 3) necrosis and infiltrates with lymphocytes and plasma cells. Conclusions Interferon beta hepatotoxicity occurs mostly in women and has a variable, but often prolonged time to onset. Most patients have self-limited acute hepatocellular liver injury but several have required liver transplantation or died of acute liver failure. Liver histology available in three cases demonstrated zone 3 necrosis and autoimmune features suggestive of an immunologic basis to this adverse drug reaction.