Hepatitis E virus infection in acute non-traumatic neuropathy: A large prospective case-control study in China

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.