Wild boar as an important reservoir of hepatitis E virus in western Japan

Hepatitis E was classically considered as a waterborne outbreak of acute hepatitis with jaundice in the tropics and subtropics. It was even regarded that most, if not all, hepatitis E cases observed in industrialized countries, including Japan, were most likely “imported.” Over the last few years, however, autochthonous hepatitis E infection has been reported from economically developed countries such as the USA, Japan, Europe and Australia.1–3 The hepatitis E virus (HEV) is the sole member of the genus Hepevirus in the family Hepeviridae, remotely related to Caliciviridae viruses.4 The interstrain sequence diversity of its genome allows four convenient groupings to be made. These include: genotype 1, which is regularly identified in human cases of hepatitis E in hyperendemic areas; genotype 2, characterized from human cases in an outbreak in Mexico and more recently in Nigeria; genotype 3, which is detected in humans with non-imported disease and in pigs of economically developed countries, such as the US and Japan; and genotype 4, found among humans and pigs in east Asia.5,6 In 2001, an HEV strain of genotype 3 was isolated from a Japanese patient with acute hepatitis who had never been abroad.2 Consequent studies revealed that a Japanese indigenous strain might be circulating in the country.7,8 Furthermore, a zoonotic transmission of HEV has been suggested, with both indirect9–11 and direct12,13 evidence provided. However, the extent and impact of zoonotic transmission of acute hepatitis E occurrence has not yet been elucidated. Anti-HEV IgG has been detected among pigs in nonendemic countries such as Australia, Canada, Germany, New Zealand, the US and Japan.11,14,15 Other than in pigs, a presence of antibody to HEV and/or HEV-RNA has been proven in mice, rats, cats, monkeys, goats, cows, deer, mongooses and chickens.16–20 The zoonotic infection of HEV was first confirmed between deer and humans.12 The genomic sequence of HEV from patients of hepatitis E was identical to that found in a leftover portion of deer meat which the patients had eaten before the onset of hepatitis. Shortly after the report, two and 11 cases of hepatitis E possibly associated to wild boar ingestion were reported.21,22 Accordingly, pigs, boar and deer have been considered as important reservoirs in Japan and, naturally, pigs are considered to be the likely primary reservoir among these three. Indeed, in Hokkaido, where pig meat consumption is relatively high in comparison to other parts of Japan, a higher incidence of hepatitis E has been noted.7,8,23 On the other hand, sporadic cases or small outbreaks of hepatitis E reported in western Japan are often associated with boar ingestion.13,21,22,24–26 Therefore, information on the prevalence of anti-HEV and HEV-RNA among wild boar in western Japan appears to be of importance. Sonoda et al.27 reported that antibody to HEV was detected in 9% of 35 wild boar and in 2% of 117 wild deer tested, and HEV-RNA was detected in a boar, thus indicating an HEV-RNA prevalence of 1/35 (2.86%) among wild boar. It was not clear from Sonoda’s data whether the prevalence of HEV among boar was higher in (a) particular part(s) of Japan, probably because of limitations in the sample size. In contrast, in this issue of this journal, Michitaka et al.28 report a high prevalence of anti-HEV both in wild-caught (25.5%) and bred boar (71.4%) in the Ehime prefecture of Japan, where a case of hepatitis E in a woman who had cooked and eaten wild boar meat has recently been reported.26 The positive rates of anti-HEV showed a significant difference between wild-caught boar and bred boar (25.5% vs. 71.4%, P < 0.001). Interestingly, despite the high rate of anti-HEV, none of the bred boar was positive for HEV-RNA, and these findings were similar to the reported case of bred swine, in which viremia was recognized only within 6 months of birth.11 Furthermore, in some of the anti-HEV-positive boar, the genotype 3 HEV was detected, suggesting that genotype 3 HEV is prevalent among the boar in Ehime prefecture. Interestingly, most cases of sporadic hepatitis E in western Japan are associated with the HEV of genotype 3. Such accumulated evidence therefore seems to indicate that wild boar are one of the major reservoirs of HEV in western Japan. This assumption may be biased by patients’ memories, for example pork ingestion, which is usual in Japan, is less memorable than boar ingestion, which does not appear to be a usual food item, even for those who like eating wild animals. It is possible, therefore, that the wild boar-borne transmission of HEV is overestimated, while pig-borne transmission remains underrepresented due to such a recall bias. Indeed, it has been shown that over 50% of Japanese hepatitis E patients have an unknown mode of transmission.29 Nevertheless, there is no doubt that the consumption of boar meat puts individuals at a high risk of developing hepatitis E infection in western Japan. As Michitaka et al. concluded, boar should be regarded as an important reservoir of HEV and caution is therefore required in cooking and eating boar meat.