Title: Prevalence of Hepatitis E virus infection among Japanese blood donors
Abstract: ISBT Science SeriesVolume 4, Issue n2 p. 299-301 Free Access Prevalence of Hepatitis E virus infection among Japanese blood donors H. Ikeda, H. Ikeda Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorK. Matsubayashi, K. Matsubayashi Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorH. Sakata, H. Sakata Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorH. Takeda, H. Takeda Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorS. Sato, S. Sato Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorT. Kato, T. Kato Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorS. Hino, S. Hino Japanese Red Cross Blood Service Headquarters, Tokyo, JapanSearch for more papers by this authorK. Tadokoro, K. Tadokoro Japanese Red Cross Blood Service Headquarters, Tokyo, JapanSearch for more papers by this author H. Ikeda, H. Ikeda Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorK. Matsubayashi, K. Matsubayashi Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorH. Sakata, H. Sakata Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorH. Takeda, H. Takeda Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorS. Sato, S. Sato Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorT. Kato, T. Kato Japanese Red Cross Hokkaido Blood Center, Hokkaido, JapanSearch for more papers by this authorS. Hino, S. Hino Japanese Red Cross Blood Service Headquarters, Tokyo, JapanSearch for more papers by this authorK. Tadokoro, K. Tadokoro Japanese Red Cross Blood Service Headquarters, Tokyo, JapanSearch for more papers by this author First published: 14 October 2009 https://doi.org/10.1111/j.1751-2824.2009.01258.xCitations: 2 Hisami Ikeda, Japanese Red Cross Hokkaido Blood Center Yamanote 2–2, Nishi-Ku, Sapporo 063-002, Japan E-mail: [email protected] PS02 AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Hepatitis E virus (HEV) infection has been considered to occur via faecal–oral transmission and is an important public health concern in developing countries, while such HEV transmission had been recognized to be extremely rare in industrialized countries including Japan. Recently, however, increasing cases of hepatitis E are reported in Japan and several cases are described as transfusion–transmission. Many reports from Japan suggest that eating undercooked meat and/or liver of pigs and other animals is associated with a high risk of acquiring HEV infection. According to the reports by Japanese investigators including ourselves, the HEV RNA-positive donors had no history of recent travel abroad in areas where HEV was hyperendemic [1]. Some isolates from the HEV RNA positive donor samples showed close sequence homology with the isolates from pigs in Japan, indicating that HEV transmission is probably associated with the consumption of undercooked or inadequately cooked pig meat [2]. Thus, HEV is regarded as a zoonotic agent in Japan. Characteristics of hepatitis E in Japan can be summarized as follows. More than 200 cases of hepatitis E have been recently reported [3]. The patients are dominantly middle- or high-aged males. The isolated HEVs are genotype 3 and genotype 4 and regarded as indigenous strains in Japan. Genotype 4 viruses may cause more serious symptoms. In about 60% of the cases, their routes of infection remain unknown, although 31% of the cases are confirmed to be zoonotic food-borne. There are several reported cases of transfusion–transmission. So far, we have experienced four cases of transfusion-transmitted hepatitis E (TTHE). In 2004, we reported the first molecularly confirmed case of TTHE. However, infection route of the causative donor was not very clear. To assess the risk of the transfusion–transmission of HEV, we started a series of HEV surveys in blood donors of Hokkaido and nationwide Japan. For the surveys of HEV prevalence in blood donors, we tested samples of the donors who were disqualified due to high ALT level over 200 IU/l [4]. Samples of donors with ALT elevation during the 1-year period from April 2003 were collected from all-over Japan and tested for HEV markers: IgM anti-HEV, IgG anti-HEV and HEV RNA. As for donors with ALT elevation, Hokkaido was the highest region for all three HEV markers. Also, HEV prevalence was higher in eastern Japan than in western Japan. Among HEV markers of donors with ALT elevation, positive rate of IgG anti-HEV showed clear age-dependency, while there was no age-dependency in IgM anti-HEV or HEV RNA. In the next step, we tested the HEV prevalence of qualified donors. Age- and gender-matched samples of qualified donors were collected from all-over Japan. Again, higher prevalence of HEV IgG was observed in eastern Japan. The positive rates in female donors were lower than that in male donors. There is a clear age-dependency in IgG anti-HEV prevalence in qualified donors. As for IgM anti-HEV, positive samples were too few to draw any conclusion. Meanwhile, we experienced the second case of TTHE [5]. After this second case of TTHE, we decided to implement preliminary HEV NAT screening in Hokkaido. However, after the start of this trial NAT, we experienced two additional cases of TTHE in 2005 and 2006. In the trial NAT, it took almost a week to obtain the results of HEV NAT and some of the blood products, especially platelets, were already transfused before NAT. In 2006, we implemented on-time NAT screening and we have not received a case of TTHE since then. The reasons that the HEV NAT screening has been so far limited only in Hokkaido are (1) transfusion–transmission of HEV as well as sporadic cases of hepatitis E were reported at the highest frequency in Hokkaido, (2) HEV prevalence among blood donors appeared to be the highest in Hokkaido and (3) the HEV strain of genotype 4, which is more virulent than genotype 3, was distributed exclusively in Hokkaido. The second case of TTHE is very important to us, because the infection route of the causative donor was able to be confirmed through the investigation of this case. The donor was found to be HEV NAT positive on 20 September 2004. Look-back survey revealed that his previous donation on September 6 was also HEV RNA-positive. However, his donated platelets were already transfused to the patient, who was found to be HEV infected through the platelet concentrate from the HEV-positive donor. The HEV isolates of both patients and platelets were identical. About 3 weeks before the first donation, the causative donor had a barbecue party at a restaurant with his family and enjoyed yakiniku dinner including pig liver and/or intestines. One of the family members was his father. Father died of fulminant hepatitis E 60 days after the barbecue party. HEV isolates from the donor also showed 99·9% homology with the isolate from his father based on nearly entire HEV genome. They were classified as genotype 4 and regarded to be indigenous to Hokkaido. Other members of the family who joined the dinner at the barbecue restaurant were tested for HEV markers in the samples taken up to 90 days after the dinner. Of 13 members, seven were positive for the markers, six of whom including the donor and his father were positive for HEV IgM, indicating they had been recently infected. Except for the donor and his father, HEV RNA was not detected, probably because the blood samples from the family member other than the donor and his father were taken about 90 days after the barbecue party. It is very likely that this mini-outbreak of HEV infection in the family was caused by the meals at the barbecue party. It should be noted that the causative donor and his family member who were positive for HEV markers remained asymptomatic except the father who died of fulminant hepatitis indicating the possibility that there are HEV carriers among blood donors in Japan and HEV infection does not necessarily lead to hepatitis symptoms. For this possibility, we carried out the surveys of HEV RNA prevalence in blood donors. As mentioned previously, HEV NAT has been performed for blood donors in Hokkaido since January 2005. Up to the end of 2008, number of HEV NAT-positive donors are 142. Frequency of positive donors is 1/7700, which is about half of HCV-positive frequency among donors in Hokkaido. Male positive donors were dominant. Also, genotype 3 was a dominant genotype. Some of the HEV RNA-positive donors were able to be followed up at least twice a month. About half of the donors showed the elevation of their ALT level above 45 IU/l during follow-up period. In all of the HEV RNA-positive donors, ALT level came down below 45 IU/l within 50 days after their donation. The HEV RNA-positive donors were also followed-up for their HEV RNA. In all of them, HEV RNA became under the detectable level up to 62–76 days after the donation. The significant increase of the virus level after the donation was observed in 43% of the donors. One of them was infected with genotype 4 and its doubling time appeared to be much faster than that of genotype 3. Despite transient viraemia and ALT elevation, most of them appeared to remain asymptomatic. Compared with hepatitis E patients, (1) HEV NAT-positive donors were younger, (2) genotype 3 is dominant in contrast to genotype 4 dominance in hepatitis patients. The HEV NAT positive donors were subjected to look-back as well as follow-up. The look-back study revealed three cases of HEV positive transfusion and none of the cases resulted in TTHE. It is likely that in Japan, the major route of HEV infection of the donors can be zoonotic food borne, namely pig meat. We performed the sequence analyses of HEV isolates from NAT-positive blood donors. Most of the representative strains of human isolates showed over 93% homology with the corresponding swine isolates. The results strongly suggest that most of HEV are from pigs through food-borne routes. In summary, (1) HEV prevalence in blood donors was higher in eastern Japan than in western Japan, (2) prevalence of IgG anti-HEV was age-dependent and did not show any association with HEV-RNA or IgM anti-HEV, (3) HEV NAT screening in Hokkaido revealed: (a) frequency of HEV RNA-positive donors was 1/7700, (b) male vs. female was 2·8 vs. 1, (c) mostly seronegative and/or IgM anti-HEV positive, (d) genotype 3 dominant and (e) close sequence homology to swine HEV isolates. Therefore, zoonotic food-borne route is most likely to be the main route of HEV infection in Japan. Follow-up of those HEV-positive donors revealed that most of them remained asymptomatic. References 1 Matsubayashi K, Nagaoka Y, Sakata H, Sato S, Fukai K, Kato T, Takahashi K, Mishiro S, Imai M, Takeda N, Ikeda H: Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E virus strain in Hokkaido, Japan. Transfusion 2004; 44: 934– 940 Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 2 Yazaki Y, Mizuo H, Takahashi M, Nishizawa T, Sasaki N, Gotanda Y, Okamoto H: Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be food-borne, as suggested by the presence of hepatitis E virus in pig liver as food. J Gen Virol 2003; 84: 2351– 2357 CrossrefCASPubMedWeb of Science®Google Scholar 3 Abe T, Aikawa T, Akahane Y, Arai M, Asahina Y, Atarashi Y, Chayama K, Harada H, Hashimoto N, Hori A, Ichida T, Ikeda H, Ishikawa A, Ito T, Kang J-H, Karino Y, Kato H, Kato M, Kawakami M, Kitajima N, Kitamura T, Masaki N, Matsubayashi K, Matsuda H, Matsui A, Michitaka K, Mihara H, Miyaji K, Miyakawa H, Mizuo H, Mochida S, Moriyama M, Nishiguchi S, Okada K, Saito H, Sakugawa H, Shibata M, Suzuki K, Takahashi K, Yamada G, Yamamoto K, Yamanaka T, Yamato H, Yano K, Mishiro S: Demographic, epidemiological, and virological characteristics of hepatitis E virus infections in Japan based on 254 human cases collected nationwide. Kanzo 2006; 47: 384– 391 CrossrefGoogle Scholar 4 Sakata H, Matsubayashi K, Takeda H, Sato S, Kato T, Hino S, Tadokoro K, Ikeda H: A nationwide survey for hepatitis E virus prevalence in Japanese blood donors with elevated alanine aminotransferase. Transfusion 2008; 48: 2568– 2576 Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 5 Matsubayashi K, Kang J-H, Sakata H, Takahashi K, Shindo M, Kato M, Sato S, Kato T, Nishimori H, Tsuji K, Maguchi H, Yoshida J, Maekubo H, Mishiro S, Ikeda H: A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food-borne route. Transfusion 2008; 48: 1368– 1375 Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Citing Literature Volume4, Issuen2Special Issue: State of the Art Presentations. XXth Regional Congress of the ISBT, Asia; Nagoya, Japan; November 14-18, 2009.November 2009Pages 299-301 ReferencesRelatedInformation