Hepatitis E Virus Infection in Acute Non-Traumatic Neuropathy: A Large Prospective Case-Control Study in China

Abstract

Neurological manifestations are potentially associated with hepatitis E virus (HEV) infection in Europe, mainly attributed to genotype (GT) 3 HEV infection. In this study, we determined the frequency and causal relationship of HEV in patients with non-traumatic neurological disorders in China, where GT4 HEV is prevalent. 1117 consecutive patients diagnosed with neurological illnesses in a hospital of eastern China and 1475 healthy controls who took routine examination in the same hospital were tested for HEV by serology and molecular methods. Anti-HEV IgM antibodies were detectable in 6 (0.54%) of the patients and 10 (0.68%) of the healthy controls (P = 0.651). Serum HEV RNA was detected in all of the 16 individuals with positive anti-HEV IgM. The six patients with HEV infection included two viral encephalitis, two posterior circulation ischemia, one peripheral neuropathy and one Guillian-Barré syndrome. They had no symptoms of acute viral hepatitis except two patients of viral encephalitis that showed mildly transaminitis. Additional, 39.51% patients and 35.63% controls without acute HEV infection were positive for anti-HEV IgG (P = 0.144). Anti-HEV IgG positivity was more frequent in male and elderly in both the patients and control groups, but unrelated to the incidence of any non-traumatic neurological illness, hospital stay or treatment outcome, except linking to better outcome of hemorrhagic stroke disease. These data demonstrated that HEV appears not to contribute to acute neurological disorders in China. Nevertheless, we cannot exclude a possible causative role, suggesting that testing HEV in this population, especially in situations of unexplained deregulated liver function would be warranted.a Student t-test for normally distributed continuous variables whereas other continuous variables were expressed in median (interquartile range [IQR]); the data with skewed distribution were compared using the Mann-Whitney U test; Chi-squared or the Fisher's exact test for categorical variables with excepted cell sizes less than five were used. b There is no treatment failure patient in both anti-HEV IgG positive and negative cohorts.Y. Wang et al. / EBioMedicine xxx (xxxx) xxx-xxx

Incidence, predictors and prognosis of genotype 4 hepatitis E related liver failure: A tertiary nested case‐control study

“…Serum HEV RNA detection and sequence analysis were performed as before . Total RNA was extracted from serum using the QIAamp Viral RNA mini‐kit (Qiagen, Germany) according to the manufacturer's instructions.…”

Extrahepatic manifestations of hepatitis E virus: An overview

“…19 However, a study from China compared the prevalence of acute hepatitis E between 1,117 patients diagnosed with neurological illness and 1,475 healthy controls and found that there was no difference (0.54% vs. 0.68%). 20 A possible explanation is the geographical distribution of HEV. The study from China was conducted in an area endemic for HEV genotype 4, while the European studies reported cases associated with HEV genotype 3.…”

Extrahepatic manifestations and HEV, the genotype matters

“…In particular, pancreatitis has been associated with HEV GT 1 infections, while neurological diseases as neuralgic amyotrophy or Guillain-Barré syndrome have been observed in patients with GT 3 infections. One of the most impressive studies regarding this topic was the paper by Dalton et al [ 5 ]. They studied the prevalence of acute HEV infections in a large cohort of neurological patients presenting with various non-traumatic acute neurological diseases.…”

“…In EBioMedicine , Wang et al studied a similar approach from China, an area endemic for GT 4 [ 5 ]. They enrolled 1117 patients with neurological illness and 1475 healthy controls and tested them for HEV and anti-HEV.…”

“…However, what is true for Guillain-Barré syndrome does not need to be true in neuralgic amyotrophy. The main factor is the geographical distribution of HEV, as it can be assumed that the European studies reported solely HEV GT 3 associated cases, and the study by Wang et al reported HEV GT 4 associated infections [ 5 ].…”