Hepatitis E virus infection and acute non-traumatic neurological injury: A prospective multicentre study

J Hepatol. 2017 Nov;67(5):925-932. doi: 10.1016/j.jhep.2017.07.010. Epub 2017 Jul 20.


Background & aims: Hepatitis E virus (HEV) has been associated with a number of neurological syndromes, but causality has not yet been established. The aim of this study was to explore the relationship between HEV and neurological illness by prospective HEV testing of patients presenting with acute non-traumatic neurological injury.

Methods: Four hundred and sixty-four consecutive patients presenting to hospital with acute non-traumatic neurological illnesses were tested for HEV by serology and PCR from four centres in the UK, France and the Netherlands.

Results: Eleven of 464 patients (2.4%) had evidence of current/recent HEV infection. Seven had HEV RNA identified in serum and four were diagnosed serologically. Neurological cases in which HEV infection was found included neuralgic amyotrophy (n=3, all PCR positive); cerebral ischemia or infarction (n=4); seizure (n=2); encephalitis (n=1); and an acute combined facial and vestibular neuropathy (n=1). None of these cases were clinically jaundiced and median ALT at presentation was 24IU/L (range 8-145). Cases of HEV-associated neuralgic amyotrophy were found in each of the participating countries: all were middle-aged males with bilateral involvement of the brachial plexus.

Conclusions: In this cohort of patients with non-traumatic neurological injury, 2.4% had evidence of HEV infection. Symptoms of hepatitis were mild or absent and no patients were jaundiced. The cases of HEV-associated neuralgic amyotrophy had similarities with other HEV-associated cases described in a large retrospective study. This observation supports a causal relationship between HEV and neuralgic amyotrophy. To further understand the relevance of HEV infection in patients with acute neurological illnesses, case-control studies are warranted. Lay summary: Hepatitis E virus (HEV), as its name suggests, is a hepatotropic virus, i.e. it causes damage to the liver (hepatitis). Our findings show that HEV can also be associated with a range of injury to the nervous system.

Keywords: Epidemiology; Hepatitis E virus (HEV); Neuralgic amyotrophy; Seizure; Stroke.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brachial Plexus Neuritis* / diagnosis
  • Brachial Plexus Neuritis* / epidemiology
  • Brachial Plexus Neuritis* / etiology
  • Brain Ischemia* / diagnosis
  • Brain Ischemia* / epidemiology
  • Brain Ischemia* / etiology
  • Female
  • France / epidemiology
  • Hepatitis Antibodies / blood
  • Hepatitis E virus* / genetics
  • Hepatitis E virus* / pathogenicity
  • Hepatitis E* / complications
  • Hepatitis E* / epidemiology
  • Hepatitis E* / immunology
  • Hepatitis E* / virology
  • Humans
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Neurologic Examination / methods
  • Pilot Projects
  • RNA, Viral / analysis
  • Seizures* / diagnosis
  • Seizures* / epidemiology
  • Seizures* / etiology
  • Serologic Tests / methods
  • Statistics as Topic
  • United Kingdom / epidemiology


  • Hepatitis Antibodies
  • RNA, Viral