Neuropathies related to hepatitis E virus infection: A prospective, matched case–control study

Abstract

BackgroundAcute hepatitis E virus (HEV) infection recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking.AimsTo compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain‐Barré syndrome (GBS), and Bell's palsy with a matched control population.MethodsSwiss multicentre, prospective, observational matched case‐control study over 3 years (09.2019‐10.2022). Neurological cases with NA, GBS or Bell's palsy were recruited within 1 months from disease onset. Healthy controls were matched for age, sex, geographical location, and timing of blood collection. Diagnostic criteria for acute hepatitis E were reactive serum anti‐HEV IgM and IgG assays (ELISA test) and/or HEV RNA detection in serum by Real‐time‐PCR (RT‐PCR). RT‐PCR was performed on sera to confirm IgM positivity.ResultsWe included 180 patients (59 GBS, 51 NA, and 70 Bell's palsy cases) and corresponding matched controls (blood donors), with median age of 51 years for both groups and equal gender distribution.Six IgM+ cases were detected in the NA, two in the GBS, and none in the Bell's palsy group. Two controls were anti‐HEV IgM positive. At disease onset, most cases with acute HEV infection had increased liver enzymes. A moderate association (p=0.027; Cramér's V = ‐0.25, Fisher exact test) was observed only between acute HEV infection and NA.ConclusionThis prospective observational study suggests an association between concomitant acute HEV infection and NA, but not with GBS or Bell's palsy.

Hepatitis E and diaphragmatic dysfunction: Case series and review of the literature

“…However, a simultaneous occurrence of hepatitis E, NA and diaphragmatic dysfunction has only been described in isolated cases. A multicenter, prospective, observational, matched case-control study of Rippelino et al [39], which compared the frequency of concomitant acute HEV infection in patients with NA, Guillain-Barré syndrome (GBS), and Bell's palsy with a matched control population suggests a moderate association (p = 0.027) between concomitant acute HEV infection and NA, but not with GBS or Bellʼs palsy. Because of these associations, we wondered about the prevalence of diaphragmatic dysfunction, NA and HEV infection in our clinic.…”

“…Rippelino et al [39] conducted a prospective, observational study comparing the frequency of concomitant acute HEV infection in patients with NA, Guillain-Barré syndrome (GBS), and Bellʼs palsy with a matched healthy control population. 6 IgM+ cases were detected in 51 patients with NA, two in the GBS-group (n = 59), and none in the Bellʼs palsy group (n = 70).…”

“…IJspeert et al [55] see a beneficial effect in acute phase treatment of NA with steroids or i. v. immunoglobulin. Also, Rippelino et al [39] treated the NA patients showing an acute HEV-infection with steroids. Nonetheless evidence is poor yet.…”

Reply to: ‘Letter to the Editor: Neuropathies related to hepatitis E virus infection: First reported case in Europe’

“…We fully agree that absence of evidence does not equate to evidence of absence of a relationship between hepatitis E virus (HEV) infection and Bell's palsy, and further studies should explore this association in different geographical areas and settings. However, in the hierarchy of the evidence-based medicine pyramid, results obtained in two different matched-control studies [1,2] are needed to confirm observations emerging from isolated case reports [3]. As the Spanish may be different from the Swiss situation with regards to HEV strain genotypes, we encourage Bravo Urbieta et al to set up a case-control study with adequate statistical power to finally prove or rebut the association between HEV infection and Bell's palsy because we agree that our study was not powered to detect such association.…”

Neuropathies related to hepatitis E virus infection: First reported case in Europe

“…We have read the paper by Ripellino et al [1] and wish to highlight two significant points. First, we would like to draw your attention to the case of peripheral facial paralysis as a complication of acute hepatitis E, a description of which we recently published in this very journal.…”