Molecular epidemiological analysis of hepatitis E as a zoonosis and investigation toward its prevention

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Our previous studies revealed that domestically acquired hepatitis E as a zoonosis is occurring, much more frequently than previously thought in Japan. In the present study, we aimed to clarify the molecular epidemiology of HEV infection in humans and animals and the molecular basis for pathogenesis of hepatitis E and to present possible measures for preventing HEV infection in humans based on the epidemiological surveys. We developed an enzyme-linked immunosorbent assay (ELISA) system to detect IgM and IgA classes of anti-HEV using purified recombinant ORF2 proteins expressed in the pupae of silkworm as an antigen probe and evaluated the specificity and sensitivity of these two assays. Anti-HEV IgA was found to be useful for serological diagnosis of hepatitis E with increased sensitivity and specificity. The present study revealed that the zoonotic food-borne mode of transmission of HEV from domestic pigs and wild boars to humans may play an important role in the occurrence of domestic HEV infection, and provided evidence of transfusion-transmitted HEV infection in 1979 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 in Hokkaido, where hepatitis E is most prevalent in Japan. When compared with the 7 patients with HEV genotype 3, the 25 patients with HEV genotype 4 had a significantly higher peak ALT level (P=0.0338) and a significantly lower level of lowest prothrombin activity (P=0.0340). The severe form of hepatitis E was associated with the presence of an underlying disease. Our study suggested that the HEV genotype and the presence of an underlying disease influence the severity of hepatitis E.