Highlights
- •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.
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
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.
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.
Graphical abstract
Graphical Abstract
Keywords
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References
- Hepatitis E: an emerging infection in developed countries.Lancet Infect Dis. 2008; 8: 698-709
- Hepatitis E.Lancet. 2012; 379: 2477-2488
- Hepatitis E virus and chronic hepatitis in organ-transplant recipients.N Engl J Med. 2008; 358: 811-817
- Hepatitis E virus excretion can be prolonged in patients with hematological malignancies.J Clin Virol. 2010; 49: 141-144
- Hepatitis E virus: an underestimated opportunistic pathogen in recipients of allogeneic hematopoietic stem cell transplantation.Blood. 2013; 122: 1079-1086
- Persistent carriage of hepatitis E virus in patients with HIV infection.N Engl J Med. 2009; 361: 1025-1027
- Hepatitis E virus in blood components: a prevalence and transmission study in southeast England.Lancet. 2014; 384: 1766-1773
- Hepatitis E virus infections in blood donors, France.Emerg Infect Dis. 2014; 20: 1914-1917
- No artifact, hepatitis E is emerging.Hepatology. 2015; 62: 654
- Extra-hepatic manifestations of autochthonous hepatitis E infection.Aliment Pharmacol Ther. 2014; 40: 1282-1291
- Hepatitis E virus and neurologic disorders.Emerg Infect Dis. 2011; 17: 173-179
- Hepatitis E virus and neurological injury.Nat Rev Neurol. 2016; 12: 77-85
- Genotype 3 diversity and quantification of hepatitis E virus RNA.J Clin Microbiol. 2012; 50: 897-902
- Hepatitis E virus infection among solid organ transplant recipients, The Netherlands.Emerg Infect Dis. 2012; 18: 869-872
- Past and present of hepatitis E in the Netherlands.Transfusion. 2014; 54: 3092-3096
- A comparison of two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developed countries.J Med Virol. 2010; 82: 799-805
- Diagnostic performance of selected commercial HEV IgM and IgG ELISAs for immunocompromised and immunocompetent patients.J Clin Virol. 2013; 58: 629-634
- Neuralgic amyotrophy and hepatitis E virus infection.Neurology. 2014; 82: 498-503
- Clinical phenotype and outcome in hepatitis E virus associated neuralgic amyotrophy.Neurology. 2017; (in press)
- Hepatitis E virus: Infection beyond the liver?.J Hepatol. 2017; 66: 1082-1095
- Neurologic disorders in immunocompetent patients with autochthonous acute hepatitis E.Emerg Infect Dis. 2015; 21: 1928-1934
- Acute hepatitis E infection associated with Guillain-Barré syndrome in an immunocompetent patient.Rev Med Interne. 2014; 35: 333-336
- Infectious cause of stroke.Lancet Infect Dis. 2014; 14: 869-880
- Chickepox and risk of stroke: a self-controlled case series analysis.Clin Infect Dis. 2014; 58: 61-68
- Hepatitis E infection with Bell's palsy.J Assoc Physicians India. 2006; 54: 418
- Characteristics of 20 Patients with Autochthonous Acute Hepatitis E in Hokkaido, Japan: First Report of Bilateral Facial Palsy Following the Infection with Genotype 4 Hepatitis E Virus.Tohoku J Exp Med. 2015; 236: 263-271
- Infections in the differential diagnosis of Bell's palsy: a plea for performing CSF analysis.Infection. 2016;
- Guillain-Barre syndrome associated with preceding hepatitis E virus infection.Neurology. 2014; 82: 491-497
- Hepatitis E and Guillain-Barre syndrome.Clin Infect Dis. 2013; 57: 1369-1370
- Guillain-Barre and Miller Fisher syndromes in patients with anti-hepatitis E virus antibody: a hospital-based survey in Japan.Neurol Sci. 2016; 37: 1849-1851
- Diagnostic challenges and clinical characteristics of hepatitis E virus-associated Guillain-Barré syndrome.JAMA Neurol. 2017; 74: 26-33
- Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells.J Viral Hepat. 2016; 23: 512-521
- Evidence of Hepatitis E virus breaking through the blood-brain barrier and replicating in the central nervous system.J Viral Hepat. 2016; https://doi.org/10.1111/jvh.12557
- A nationwide survey of hepatitis E viral infection in French blood donors.Hepatology. 2016; 63: 1145-1154
Article info
Publication history
Published online: July 19, 2017
Accepted:
July 10,
2017
Received in revised form:
June 22,
2017
Received:
April 22,
2017
Identification
Copyright
© 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
