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

Autochthonous hepatitis E is increasingly being recognized in industrialized countries, including Japan. Although neurological abnormalities have been sporadically reported as an extrahepatic manifestation of hepatitis E virus (HEV) infection, it is rare and has not been reported in Japan. The present study aimed to characterize a total of 20 patients consecutively diagnosed with sporadic acute hepatitis E at a city hospital in Hokkaido, Japan, during 2001-2014, focusing on a patient complicated with neuropathy. Seventeen patients were infected with genotype 4 HEV, while the remaining three patients were with genotype 3 HEV. Although a 67-year-old male with severe hepatitis did not have predisposing factors associated with the development of neurological disorders, such as diabetes mellitus and the use of immunosuppressive agents, he developed bilateral peripheral facial palsy six days after admission. A neurological examination revealed the inability to smile, frown, close his eyes completely or puff out his cheeks. MRI brain scans were considered to be normal. Although it took 83 days after admission for the total bilirubin levels to normalize, his neurological symptoms resolved gradually within three weeks without any sequelae following conservative therapy. A full-length genomic analysis of the HEV strain (HE-JA30) isolated from the patient belonged to genotype 4 and was closest to that currently circulating in Hokkaido, Japan. This is the first report of HEV-associated neuropathy in Japan. While all of previous reports on HEV-related neuropathy involve genotype 3 HEV, the present report is unique in that genotype 4 HEV is responsible for the neuropathy.