Original article
Pancreas, biliary tract, and liver
Hepatitis E Virus Infection as a Possible Cause of Acute Liver Failure in Europe

https://doi.org/10.1016/j.cgh.2015.04.014Get rights and content

Background & Aims

In Western countries, infection with the hepatitis E virus (HEV) is considered to be rare and imported from endemic regions. However, the prevalence of HEV infection has increased among adults in central Europe. HEV infection can cause acute liver failure (ALF), but there have been only a few confirmed cases of HEV-associated ALF in Europe. We investigated the number of cases of indeterminate ALF associated with HEV infection.

Methods

We performed a retrospective analysis of 80 patients diagnosed with ALF or acute hepatitis at the University Hospital Essen in Germany from November 2006 through December 2013. Clinical data were collected from the hospital databases; archived sera were tested for IgG and IgM against HEV, as well as HEV RNA.

Results

Sera from 12 patients (15%) tested positive for IgG against HEV IgG; 7 of these samples did not test positive for HEV IgM or HEV RNA. Sera from 64 patients (80%) did not test positive for IgG or IgM against HEV or HEV RNA. Sera from 8 patients (10%) tested positive for HEV RNA (only 4 of these were positive for HEV IgG) and had clinical findings to support acute HEV infection.

Conclusions

In a hospital in Germany, approximately 10% to 15% of patients with ALF had evidence for HEV infection. Serologic tests for IgG against HEV are insufficient to identify or exclude HEV infection; tests for HEV RNA also should be performed on patients with ALF of ambiguous etiology.

Section snippets

Patient Identification

The study was performed according to the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice Guideline. In a retrospective monocenter study (November 2006 to December 2013), 80 patients were recruited with a diagnosis of ALF. Patients were excluded if they did not meet the criteria defined by the Acute Liver Failure Study Group Germany.11 In brief, ALF was diagnosed by significant liver dysfunction with pathologically increased laboratory parameters

Demographic and Clinical Features

Eighty patients had severe ALF according to the Acute Liver Failure Study Group Germany definition. The median age of all ALF patients was 41 years. Forty-nine patients (61%) were female. The most prevalent etiology was drug-induced liver failure (38%), including acetaminophen-induced liver failure and idiosyncratic drug-induced liver injury (DILI), followed by viral hepatitis (hepatitis A and B). These numbers are consistent with previous studies in Germany and other parts of Europe.11, 15

Discussion

In Europe, hepatitis E has been regarded as an imported infection from endemic regions. Recently, the rate of new HEV infections in Europe has increased,5 and currently in Western countries the impact of hepatitis E for nontraveling, immunocompetent persons is underestimated.16, 17

Our study suggests that hepatitis E contributes to a substantial proportion of acute liver injury cases in developed countries.12, 18 In our cohort, 8 of 80 ALF cases were detected to be potentially hepatitis

References (35)

  • N. Pavio et al.

    Hepatitis E in high-income countries

    Curr Opin Infect Dis

    (2010)
  • J.J. Wenzel et al.

    Test performance characteristics of anti-HEV IgG assays strongly influence hepatitis E seroprevalence estimates

    J Infect Dis

    (2013)
  • H.C. Lewis et al.

    Transmission routes and risk factors for autochthonous hepatitis E virus infection in Europe: a systematic review

    Epidemiol Infect

    (2010)
  • O. Parkash et al.

    MELD score: utility and comparison with King’s College criteria in non-acetaminophen acute liver failure

    J Coll Physicians Surg Pak

    (2012)
  • S.K. Acharya et al.

    Acute hepatic failure in India: a perspective from the East

    J Gastroenterol Hepatol

    (2000)
  • R.J. Fontana et al.

    The role of hepatitis E virus infection in adult American patients with acute liver failure

    Hepatology

    (2012)
  • M.H. Kuniholm et al.

    Epidemiology of hepatitis E virus in the United States: results from the Third National Health and Nutrition Examination Survey, 1988-1994

    J Infect Dis

    (2009)
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    This article has an accompanying continuing medical education activity on page e158. Learning Objective–Upon completion of this activity, successful learners will be able to diagnose possible cases of hepatitis E virus associated liver failure.

    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by the Deutsche Forschungsgemeinschaft (267/11-1 and 267/13-1 to A.C.) and by the Wilhelm-Laupitz Foundation to AC.

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