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Presentation and outcomes with clinically apparent interferon beta hepatotoxicity.
Dig Dis Sci. 2013 Jun; 58(6):1766-75.DD

Abstract

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.

Authors+Show Affiliations

Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, University of Michigan Medical Center, 3912 Taubman Center, Ann Arbor, MI 48109-0362, USA. rfontana@med.umich.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Multicenter Study

Language

eng

PubMed ID

23377559

Citation

Fontana, Robert J., et al. "Presentation and Outcomes With Clinically Apparent Interferon Beta Hepatotoxicity." Digestive Diseases and Sciences, vol. 58, no. 6, 2013, pp. 1766-75.
Fontana RJ, Hayashi P, Bonkovsky HL, et al. Presentation and outcomes with clinically apparent interferon beta hepatotoxicity. Dig Dis Sci. 2013;58(6):1766-75.
Fontana, R. J., Hayashi, P., Bonkovsky, H. L., Kleiner, D. E., Kochhar, S., Gu, J., & Ghabril, M. (2013). Presentation and outcomes with clinically apparent interferon beta hepatotoxicity. Digestive Diseases and Sciences, 58(6), 1766-75. https://doi.org/10.1007/s10620-012-2553-1
Fontana RJ, et al. Presentation and Outcomes With Clinically Apparent Interferon Beta Hepatotoxicity. Dig Dis Sci. 2013;58(6):1766-75. PubMed PMID: 23377559.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Presentation and outcomes with clinically apparent interferon beta hepatotoxicity. AU - Fontana,Robert J, AU - Hayashi,Paul, AU - Bonkovsky,Herbert L, AU - Kleiner,David E, AU - Kochhar,Sweta, AU - Gu,Jiezhun, AU - Ghabril,Marwan, Y1 - 2013/02/02/ PY - 2012/05/01/received PY - 2012/12/24/accepted PY - 2013/2/5/entrez PY - 2013/2/5/pubmed PY - 2013/8/27/medline SP - 1766 EP - 75 JF - Digestive diseases and sciences JO - Dig. Dis. Sci. VL - 58 IS - 6 N2 - 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. SN - 1573-2568 UR - https://www.unboundmedicine.com/medline/citation/23377559/Presentation_and_outcomes_with_clinically_apparent_interferon_beta_hepatotoxicity_ L2 - https://doi.org/10.1007/s10620-012-2553-1 DB - PRIME DP - Unbound Medicine ER -