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

Neurological manifestations are potently associated with hepatitis E virus (HEV) infection in Europe, mainly attributed to genotype (G) 3 HEV infection. We determined the frequency and causal relationship of HEV in patients with non-traumatic neurological disorders in China, where G4 HEV is prevalent. Consecutive patients diagnosed with neurological illnesses and individuals visiting the physical examination center in a hospital of eastern China were tested for HEV by serology and molecular method. 1117 patients and 1475 healthy controls were enrolled. 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. The six patients with positive anti-HEV IgM included two viral encephalitis, two posterior circulation ischemia, one peripheral neuropathy and one Guillian-Barre syndrome. They had no symptoms of acute viral hepatitis except two patients of viral encephalitis had mildly transaminitis. Additional, 39.51% patients and 35.63% controls without acute HEV infection were anti-HEV IgG positive (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 demonstrate that HEV appears not to contribute to acute neurological disorders in China. Nevertheless, we cannot exclude a possible causative role, suggesting that testing for HEV in this population, especially in situations of unexplained deregulated liver function would be warranted. Funding Statement: This study was supported by National Natural Science Foundation of China (No. 31770186) (to Y. Wang) Declaration of Interests: The authors have declared that no competing interests exist. Ethics Approval Statement: The standard protocol, ethical approvals and registrations of this study were approved by an ethical standards committee of The First People's Hospital of Yancheng City and all patients gave informed consent that allowed future testing of archived bio-samples.