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Epstein–Barr Virus (EBV) Related Acute Liver Failure: A Case Series from the US Acute Liver Failure Study Group

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Abstract

Purpose

Acute liver failure (ALF) is a rare clinical syndrome associated with a high case fatality rate. Asymptomatic primary infection with Epstein–Barr virus (EBV) is common in the general population while acute hepatitis and jaundice are much less common and ALF has been rarely reported. We reviewed the presenting features as well as clinical outcomes amongst consecutive adults with EBV-related ALF.

Methods

Amongst the 1,887 adult ALF patients enrolled into the US ALF Study Group from January 1998 to February 2012, there were four patients (0.21 %) with EBV-related ALF. Diagnostic criteria for acute EBV infection included compatible serologies and/or the detection of EBV-encoded RNA (EBER) in liver tissue.

Results

Median patient age was 30 years (range 18–44); 75 % were male, and only 25 % were immunosuppressed. The median presenting ALT was 504 IU/mL (range 156–4,920), median Alk P was 431 (range 136–1,009), and median bilirubin was 17 mg/dL (range 13–22.1). Liver biopsy findings ranged from cholestasis to submassive necrosis with EBER + staining in two of the three samples tested. Although all of the patients were treated with an antiviral agent, two died of ALF, one underwent liver transplantation (LT) and one survived with supportive care and is well at 5 years. A review of the literature identified four additional LT recipients with favorable long-term outcomes.

Conclusion

Primary EBV infection accounts for <1 % of consecutive adult ALF cases but is associated with a high case fatality rate. LT is associated with favorable short- and long-term outcomes.

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Abbreviations

ALF:

Acute liver failure

ALFSG:

Acute Liver Failure Study Group

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CMV:

Cytomegalovirus

EBER:

Epstein–Barr encoded RNA

EBV:

Epstein–Barr virus

HSV:

Herpes simplex virus

INR:

International normalized ratio

NA:

Nuclear antigen

LT:

Liver transplantation

ULN:

Upper limit of normal

VCA:

Viral capsid antigen

WBC:

White blood count

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Acknowledgments

We gratefully acknowledge the support provided by the members of The Acute Liver Failure Study Group. This study was funded by the National Institute of Diabetes, Digestive and Kidney Diseases (DK U-01-58369). Additional funding was provided by the Tips Fund of Northwestern Medical Foundation and the Jeanne Roberts and Rollin and Mary Ella King Funds of the Southwestern Medical Foundation. Additionally, Dr. Melllinger is supported by the T32 DK62708-01, NIDDK Training Grant in Gastrointestinal Epidemiology, and a Clinical and Translational Science Award from the Michigan Institute for Clinical and Health Research.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan Health System, 3912 Taubman Center, 1500 E. Medical Center Drive, SPC 5362, Ann Arbor, MI, 48109-0362, USA

    Jessica L. Mellinger & Robert J. Fontana

  2. Division of Gastroenterology and Hepatology, Davis Medical Center, University of California, Sacramento, CA, USA

    Lorenzo Rossaro

  3. Department of Medicine, Oregon Health Sciences University, Portland, OR, USA

    Willscott E. Naugler

  4. Division of Transplant Surgery, University of Michigan Health System, Ann Arbor, MI, USA

    Satish N. Nadig

  5. Department of Pathology, University of Michigan Health System, Ann Arbor, MI, USA

    Henry Appelman

  6. Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern, Dallas, TX, USA

    William M. Lee

Authors
  1. Jessica L. Mellinger
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  2. Lorenzo Rossaro
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  3. Willscott E. Naugler
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  4. Satish N. Nadig
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  5. Henry Appelman
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  6. William M. Lee
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  7. Robert J. Fontana
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Corresponding author

Correspondence to Robert J. Fontana.

Additional information

On behalf of the US Acute Liver Failure Study Group.

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Appendix

Appendix

Members and institutions participating in the Acute Liver Failure Study Group 1998–2010 are as follows: W.M. Lee, M.D. (Principal Investigator), George A. Ostapowicz, M.D., Frank V. Schiødt, M.D., Julie Polson, M.D., University of Texas Southwestern, Dallas, TX; Anne M. Larson, M.D., Iris Liou, M.D., University of Washington, Seattle, WA; Timothy Davern, M.D., University of California, San Francisco, CA (current address: California Pacific Medical Center, San Francisco, CA), Oren Fix, M.D., University of California, San Francisco; Michael Schilsky, M.D., Mount Sinai School of Medicine, New York, NY (current address: Yale University, New Haven, CT); Timothy McCashland, M.D., University of Nebraska, Omaha, NE; J. Eileen Hay, M.B.B.S., Mayo Clinic, Rochester, MN; Natalie Murray, M.D., Baylor University Medical Center, Dallas, TX; A. Obaid S. Shaikh, M.D., University of Pittsburgh, Pittsburgh, PA; Andres Blei, M.D., Northwestern University, Chicago, IL (deceased), Daniel Ganger, M.D., Northwestern University, Chicago, IL; Atif Zaman, M.D., University of Oregon, Portland, OR; Steven H.B. Han, M.D., University of California, Los Angeles, CA; Robert Fontana, M.D., University of Michigan, Ann Arbor, MI; Brendan McGuire, M.D., University of Alabama, Birmingham, AL; Raymond T. Chung, M.D., Massachusetts General Hospital, Boston, MA; Alastair Smith, M.B., Ch.B., Duke University Medical Center, Durham, NC; Robert Brown, M.D., Cornell/Columbia University, New York, NY; Jeffrey Crippin, M.D., Washington University, St Louis, MO; Edwin Harrison, Mayo Clinic, Scottsdale, AZ; Adrian Reuben, M.B.B.S., Medical University of South Carolina, Charleston, SC; Santiago Munoz, M.D., Albert Einstein Medical Center, Philadelphia, PA; Rajender Reddy, M.D., University of Pennsylvania, Philadelphia, PA; R. Todd Stravitz, M.D., Virginia Commonwealth University, Richmond, VA; Lorenzo Rossaro, M.D., University of California Davis, Sacramento, CA; Raj Satyanarayana, M.D., Mayo Clinic, Jacksonville, FL; and Tarek Hassanein, M.D., University of California, San Diego, CA. The University of Texas Southwestern Administrative Group included Grace Samuel, Ezmina Lalani, Carla Pezzia, and Corron Sanders, Ph.D., Nahid Attar, the Statistics and Data Management Group included Joan S. Reisch, Ph.D., Linda S. Hynan, Ph.D., Janet P. Smith, Joe W. Webster and Mechelle Murray, and the Medical University of South Carolina Data Coordination Unit included Valerie Durkalski, Ph.D., Wenle Zhao, Ph.D., Catherine Dillon, and Tomoko Goddard.

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Mellinger, J.L., Rossaro, L., Naugler, W.E. et al. Epstein–Barr Virus (EBV) Related Acute Liver Failure: A Case Series from the US Acute Liver Failure Study Group. Dig Dis Sci 59, 1630–1637 (2014). https://doi.org/10.1007/s10620-014-3029-2

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  • DOI: https://doi.org/10.1007/s10620-014-3029-2

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