Digestive Diseases and Sciences

, Volume 63, Issue 6, pp 1654–1666 | Cite as

Acute Liver Failure from Tumor Necrosis Factor-α Antagonists: Report of Four Cases and Literature Review

  • Beverley Kok
  • Erica L. W. Lester
  • William M. Lee
  • A. James Hanje
  • R. Todd Stravitz
  • Safwat Girgis
  • Vaishali Patel
  • Joshua R. Peck
  • Christopher Esber
  • Constantine J. Karvellas
  • for the United States Acute Liver Failure Study Group
Original Article



Tumor necrosis factor-α antagonists (anti-TNF-α) have been associated with drug-induced liver injury. However, cases of anti-TNF-α-associated acute liver failure have only been rarely reported.


To identify cases of anti-TNF-α-associated acute liver failure and evaluate patterns of liver injury and common characteristics to the cases.


The United States Acute Liver Failure Study Group database was searched from 1998 to 2014. Four subjects were identified. A PubMed search for articles that reported anti-TNF-α-associated acute liver failure identified five additional cases.


The majority of individuals affected were female (eight of nine cases). Age of individual ranged from 20 to 53 years. The most common anti-TNF-α agent associated with acute liver failure was infliximab (n = 8). The latency between initial drug exposure and acute liver failure ranged from 3 days to over a year. Of the nine cases, six required emergency LT. Liver biopsy was obtained in seven cases with a preponderance toward cholestatic–hepatitic features; none showed clear autoimmune features.


Anti-TNF-α-associated acute liver failure displays somewhat different characteristics compared with anti-TNF-α-induced drug-induced liver injury. Infliximab was implicated in the majority of cases. Cholestatic–hepatitic features were frequently found on pre-transplant and explant histology.


Drug-induced liver injury Tumor necrosis factor-α antagonists Acute liver failure Liver transplant 



Acute liver failure


Alkaline phosphatase


Alanine transaminase


Aspartate transaminase




Drug-induced liver injury


Herpes simplex virus


Human immunodeficiency virus


Intensive care unit


International normalized ratio


Liver transplant




Roussel Uclaf Causality Assessment Method


United States Acute Liver Failure Study Group


Tumor necrosis factor-α


Financial support

The study was sponsored by NIH Grant U-01 58369 (from NIDDK).

Author’s contributions

BK: Collected data and drafted individual case history, performed literature review and drafted the final manuscript. EL, WL, VP, JRP, CE: Collected data and drafted individual case histories and significantly revised final manuscript. SG: Reviewed case pathologies and significantly reviewed the final manuscript. WML: Reviewed all cases for causality and revised the final manuscript. AJH, RTS: Revised the final manuscript. CJK: Conceived the idea for the study, assisted in study design and case collection and significantly revised the final manuscript.

Data/research materials

May be requested from the United States Acute Liver Failure Study Group at Note: Two of the cases in this manuscript were described briefly in a published letter (Transplant Intl 2013 Dec; 26(12):e110-2.)

Compliance with ethical standards

Conflict of interest


Supplementary material

10620_2018_5023_MOESM1_ESM.doc (383 kb)
Supplementary material 1 (DOC 383 kb)
10620_2018_5023_MOESM2_ESM.docx (118 kb)
Supplementary material 2 (DOCX 117 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Beverley Kok
    • 1
  • Erica L. W. Lester
    • 2
  • William M. Lee
    • 3
  • A. James Hanje
    • 4
  • R. Todd Stravitz
    • 5
  • Safwat Girgis
    • 6
  • Vaishali Patel
    • 5
  • Joshua R. Peck
    • 4
  • Christopher Esber
    • 4
  • Constantine J. Karvellas
    • 1
    • 7
  • for the United States Acute Liver Failure Study Group
  1. 1.Division of Gastroenterology (Liver Unit), Department of Critical Care MedicineUniversity of AlbertaEdmontonCanada
  2. 2.Department of SurgeryUniversity of AlbertaEdmontonCanada
  3. 3.Division of GastroenterologyUniversity of Texas SouthwesternDallasUSA
  4. 4.Division of GastroenterologyOhio State UniversityColumbusUSA
  5. 5.Division of GastroenterologyVirginia Commonwealth UniversityRichmondUSA
  6. 6.Department of PathologyUniversity of AlbertaEdmontonCanada
  7. 7.Department of Critical Care MedicineUniversity of AlbertaEdmontonCanada

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