Possible risk factors for the transmission of hepatitis E virus and for the severe form of hepatitis E acquired locally in Hokkaido, Japan

Hepatitis E in industrialized countries has not been well studied. To define the possible risk factors for transmission of hepatitis E virus (HEV) and for the severe form of hepatitis E in Japan, we investigated the clinical and virological characteristics of hepatitis E in 32 patients who contracted the mild (n = 23) or severe form (n = 9) of domestically acquired hepatitis E between 1996 and 2004 in Hokkaido, where hepatitis E is most prevalent in Japan. Nine patients with the severe form of hepatitis E included two patients with fulminant hepatitis E and seven patients who were diagnosed with severe acute hepatitis in which hepatic encephalopathy did not appear during the course of the illness despite low plasma prothrombin activity (≤40%) and/or increased total bilirubin level (≥20 mg/dl). At least 25 patients (78%) had consumed uncooked or undercooked pig liver and/or intestine 1–2 months before the onset of hepatitis E. When compared with the seven patients with HEV genotype 3, the 25 patients with HEV genotype 4 had a higher peak alanine aminotransferase (ALT) level ( P  = 0.0338) and a lower level of lowest prothrombin activity ( P  = 0.0340). The severe form of hepatitis E was associated with the presence of an underlying disease (56% [5/9] vs. 17% [4/23], P  = 0.0454). The study suggests that zoonotic food‐borne transmission of HEV plays an important role in the occurrence of hepatitis E in Hokkaido, Japan, and that the HEV genotype and the presence of an underlying disease influence the severity of hepatitis E. J. Med. Virol. 76:341–349, 2005. © 2005 Wiley‐Liss, Inc.