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

我们以前的研究表明，国内获得性戊型肝炎作为一种人畜共患病正在发生，比以前认为的要频繁得多。在本研究中，我们旨在阐明人和动物HEV感染的分子流行病学和戊型肝炎发病的分子基础，并在流行病学调查的基础上提出预防人类HEV感染的可能措施。我们开发了一种酶联免疫吸附试验（ELISA）系统，以纯化的家蚕蛹中表达的重组ORF2蛋白为抗原探针，检测IgM和IgA类抗hev病毒，并评估了这两种检测方法的特异性和敏感性。发现抗戊型肝炎IgA可用于戊型肝炎的血清学诊断，具有更高的敏感性和特异性。本研究揭示了由家猪和野猪向人类传播HEV的人畜共患食源性传播模式可能在家庭HEV感染的发生中起重要作用，并为1979年日本输血传播HEV感染提供了证据。我们调查了在日本最流行戊型肝炎的北海道（北海道）感染国内获得性戊型肝炎的32例轻度（n=23）或重度（n=9）患者的临床和病毒学特征。与7例HEV基因3型患者相比，25例HEV基因4型患者ALT峰值水平显著升高（P=0.0338），凝血酶原最低活性水平显著降低（P=0.0340）。戊型肝炎的严重形式与潜在疾病的存在有关。我们的研究表明，HEV基因型和潜在疾病的存在影响戊型肝炎的严重程度。

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.