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Original Investigation
January 2017

Diagnostic Challenges and Clinical Characteristics of Hepatitis E Virus–Associated Guillain-Barré Syndrome

Author Affiliations
  • 1Department of Neurology, University Hospitals Leuven, Leuven, Belgium
  • 2Department of Neurosciences, Experimental Neurology, KU Leuven, University of Leuven, Leuven, Belgium
  • 3Laboratory for Molecular Neurobiomarker Research, KU Leuven, Leuven, Belgium
  • 4 Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
  • 5VIB, Vesalius Research Center, Leuven, Belgium
JAMA Neurol. 2017;74(1):26-33. doi:10.1001/jamaneurol.2016.3541
Key Points

Question  What is the importance of, and what are the challenges in, diagnosing an acute hepatitis E virus (HEV) infection as a preceding infection in patients with Guillain-Barré syndrome or a variant of Guillain-Barré syndrome?

Findings  This cohort study finds that acute hepatitis E virus infection is frequently associated with Guillain-Barré syndrome, presenting with a heterogeneous phenotype. Cross-reactivity with other pathogens must be taken into account to make a certain diagnosis of infection with hepatitis E virus.

Meaning  In a classic or atypical presentation of Guillain-Barré syndrome, one should consider testing the patient for an associated hepatitis E virus infection but always in parallel with testing for other pathogens, since cross-reactivity is possible.


Importance  Hepatitis E virus (HEV) recently has been shown to be an antecedent infection in Guillain-Barré syndrome (GBS), but the clinical spectrum of HEV-associated GBS is not yet documented, and diagnosing acute HEV infection can be a challenge.

Objectives  To determine the prevalence of HEV-associated GBS in a Belgian cohort, study the clinical spectrum of HEV-associated GBS, and discuss difficulties in diagnosing acute HEV infection.

Design, Setting, and Participants  This single-center, retrospective cohort study was conducted between January 1, 2007, and November 1, 2015. All patients with GBS or a GBS variant who presented to the adult neurology department of the University Hospital Leuven were identified via a search of the electronic medical records. Hepatitis E virus IgM and IgG reactivity was determined. In a subgroup, polymerase chain reaction for HEV was performed.

Main Outcomes and Measures  Hepatitis E virus IgM and IgG reactivity.

Results  Of 73 eligible patients (mean [SD] age, 52 [18] years; 29 females and 44 males), 6 (8%) showed positive reactivity on IgM assays for HEV, indicating a possible acute HEV infection. Four of the 6 patients (67%) had increased alanine aminotransferase levels of more than 1.5 times the upper limit of normal, while 4 of 22 patients (18%) with increased alanine aminotransferase levels showed positive reactivity on HEV IgM assays. Serum samples of 2 of 6 patients with positive reactivity on HEV IgM assays also revealed positive test results for cytomegalovirus or Epstein-Barr virus, indicating possible cross-reactivity. Thus, 4 patients (6%) in our cohort had probable acute HEV infection. Two of these patients presented with an infrequent GBS variant.

Conclusions and Relevance  Acute HEV infection was frequently associated with GBS in our cohort. Abnormal alanine aminotransferase levels at admission can indicate the presence of an associated HEV infection. When HEV testing is considered, it is important to test for other infectious agents in parallel, as cross-reactivity can occur. Further studies are required to guide neurologists in their workup of underlying triggers of GBS.