Research Article| Volume 67, ISSUE 5, P925-932, November 2017

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


      • 11/464 (2.4%) patients presenting with non-traumatic neurological injury had evidence of current/recent HEV infection.
      • In 7/11 cases HEV RNA was found in the serum.
      • Three cases were neuralgic amyotrophy with bilateral symptoms, which is the HEV-associated phenotype.
      • The relationship between HEV and neuralgic amyotrophy is causal.
      • The relationship between HEV and other neurological syndromes requires further study.

      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.


      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.


      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 24 IU/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.


      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.

      Graphical abstract


      Linked Article

      • Reply to: “Association of hepatitis E virus infection and myasthenia gravis: A pilot study”
        Journal of HepatologyVol. 68Issue 6
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          Hepatitis E virus (HEV) has been associated with several extrahepatic, neurological manifestations.1,2 The associated neurological syndromes are most frequently subacute, post-infectious peripheral nervous system diseases including neuralgic amyotrophy and Guillain-Barre syndrome. In addition, infectious involvement of the central nervous system (HEV encephalitis) has been reported. When the genotype has been determined, neurological injury has almost exclusively been associated with HEV genotype 3 (HEV gt3), but case reports come from both developed and developing countries suggesting that HEV-associated neurological damage is not genotype-specific.
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      • Association of hepatitis E virus infection and myasthenia gravis: A pilot study
        Journal of HepatologyVol. 68Issue 6
        • Preview
          Recently, a very important prospective multicentre study reported that 2.4% patients with non-traumatic neurological injury had evidence of current/recent hepatitis E virus (HEV) infection, highlighting the role of HEV in inducing neurological diseases.1 To date, the full spectrum of HEV-associated neurological injury is still unknown. Myasthenia gravis (MG) has been associated with a number of viral infections, such as Epstein-Barr virus (EBV),2 poliovirus,3 and Zika virus.4 One study described a woman suffering with MG as a complication of acute HEV infection.
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