Presentation and outcomes with clinically apparent interferon beta hepatotoxicity

Robert J. Fontana, Paul Hayashi, Herbert L. Bonkovsky, David E. Kleiner, Sweta Kochhar, Jiezhun Gu, Marwan Ghabril

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1766-1775
Number of pages10
JournalDigestive Diseases and Sciences
Volume58
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

Interferon-beta
Chemical and Drug Induced Liver Injury
Liver
Wounds and Injuries
Acute Liver Failure
Alanine Transaminase
Histology
Necrosis
Plasma Cells
Drug-Related Side Effects and Adverse Reactions
Causality
Liver Transplantation
Autoantibodies
Smooth Muscle
Registries
Lymphocytes
Antibodies
Serum

Keywords

  • Acute liver failure
  • Biologic response modifiers
  • Drug-induced liver injury
  • Liver biopsy
  • Multiple sclerosis

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

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), 1766-1775. https://doi.org/10.1007/s10620-012-2553-1

Presentation and outcomes with clinically apparent interferon beta hepatotoxicity. / Fontana, Robert J.; Hayashi, Paul; Bonkovsky, Herbert L.; Kleiner, David E.; Kochhar, Sweta; Gu, Jiezhun; Ghabril, Marwan.

In: Digestive Diseases and Sciences, Vol. 58, No. 6, 06.2013, p. 1766-1775.

Research output: Contribution to journalArticle

Fontana, RJ, Hayashi, P, Bonkovsky, HL, Kleiner, DE, Kochhar, S, Gu, J & Ghabril, M 2013, 'Presentation and outcomes with clinically apparent interferon beta hepatotoxicity', Digestive Diseases and Sciences, vol. 58, no. 6, pp. 1766-1775. https://doi.org/10.1007/s10620-012-2553-1
Fontana RJ, Hayashi P, Bonkovsky HL, Kleiner DE, Kochhar S, Gu J et al. Presentation and outcomes with clinically apparent interferon beta hepatotoxicity. Digestive Diseases and Sciences. 2013 Jun;58(6):1766-1775. https://doi.org/10.1007/s10620-012-2553-1
Fontana, Robert J. ; Hayashi, Paul ; Bonkovsky, Herbert L. ; Kleiner, David E. ; Kochhar, Sweta ; Gu, Jiezhun ; Ghabril, Marwan. / Presentation and outcomes with clinically apparent interferon beta hepatotoxicity. In: Digestive Diseases and Sciences. 2013 ; Vol. 58, No. 6. pp. 1766-1775.
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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.

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