{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:47:48Z","timestamp":1788918468255,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Agency for Medical Research and Development (AMED)","award":["JP20fk0210075"],"award-info":[{"award-number":["JP20fk0210075"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Recently, we experienced an outbreak of acute hepatitis A virus (HAV) infection between 2018 and 2020. Herein, we describe this male-dominant HAV infection outbreak observed among non-human immunodeficiency virus (HIV)-infected persons in the northern part of Tokyo, Japan. Clinical information was collected from patient interviews and from medical record descriptions. In the present study, 21 patients were retrospectively analyzed. A total of 90.4 and 33.3% of patients were males, and men who have sex with men (MSM), respectively. The total bilirubin levels and platelet counts tended to be lower in the MSM group than in the non-MSM group. C-reactive protein (CRP) levels tended to be higher in acute liver failure (ALF) patients than in non-ALF patients. Prolonged cholestasis was observed in one patient (4.8%). We also found that 18 HAV isolates belonged to HAV subgenotype IA\/subgroup 13 (S13), which clustered with the HAV isolate (KX151459) that was derived from an outbreak of HAV infection among MSM in Taiwan in 2015. Our results suggest that the application of antivirals against HAV, as well as HAV vaccines, would be useful for the treatment and prevention of severe HAV infection.<\/jats:p>","DOI":"10.3390\/v13020207","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T11:34:33Z","timestamp":1611920073000},"page":"207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Male-Dominant Hepatitis A Outbreak Observed among Non-HIV-Infected Persons in the Northern Part of Tokyo, Japan"],"prefix":"10.3390","volume":"13","author":[{"given":"Masayuki","family":"Honda","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Asakura","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tokyo Metropolitan Institute of Public Health, Shinjuku, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1654-5385","authenticated-orcid":false,"given":"Tatsuo","family":"Kanda","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0279-656X","authenticated-orcid":false,"given":"Yoshiko","family":"Somura","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tokyo Metropolitan Institute of Public Health, Shinjuku, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomotaka","family":"Ishii","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Yamana","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taku","family":"Mizutani","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Kumagawa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Masuzaki","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shini","family":"Kanezawa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazushige","family":"Nirei","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Yamagami","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9982-6130","authenticated-orcid":false,"given":"Naoki","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tokyo Metropolitan Institute of Public Health, Shinjuku, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Chiba","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tokyo Metropolitan Institute of Public Health, Shinjuku, Tokyo 169-0073, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiko","family":"Moriyama","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/cld.1018","article-title":"The History of Hepatitis A","volume":"16","author":"Shouval","year":"2020","journal-title":"Clin. Liver Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/med.21292","article-title":"Molecular biology and inhibitors of hepatitis A virus","volume":"34","author":"Debing","year":"2014","journal-title":"Med. Res. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Navarro, M.E.D., Yao, C.C., Whiteley, A., Movahedi, B., Devuni, D., Barry, C., Zacharias, I., Theodoropoulos, N.M., Bozorgzadeh, A., and Martins, P.N. (2020). Liver Transplant Evaluation for Fulminant Liver Failure due to Acute Hepatitis A Infection: Case-Series and Literature Review. Transpl. Infect. Dis.","DOI":"10.1111\/tid.13476"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"501","DOI":"10.5223\/pghn.2020.23.6.501","article-title":"Differential Diagnosis of Acute Liver Failure in Children: A Systematic Review","volume":"23","author":"Berardi","year":"2020","journal-title":"Pediatr. Gastroenterol. Hepatol. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nature12029","article-title":"A pathogenic picornavirus acquires an envelope by hijacking cellular membranes","volume":"496","author":"Feng","year":"2013","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kanda, T., Sasaki, R., Masuzaki, R., Matsumoto, N., Ogawa, M., and Moriyama, M. (2020). Cell Culture Systems and Drug Targets for Hepatitis A Virus Infection. Viruses, 12.","DOI":"10.3390\/v12050533"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1111\/j.1872-034X.2012.01009.x","article-title":"Hepatitis A, B, C and E virus markers in Chinese residing in Tokyo, Japan","volume":"42","author":"Yan","year":"2012","journal-title":"Hepatol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/s41598-018-37349-1","article-title":"Very low prevalence of anti-HAV in Japan: High potential for future outbreak","volume":"9","author":"Yamamoto","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"30468","DOI":"10.2807\/1560-7917.ES.2017.22.8.30468","article-title":"Hepatitis A outbreak among men who have sex with men (MSM) predominantly linked with the EuroPride, the Netherlands, July 2016 to February 2017","volume":"22","author":"Freidl","year":"2017","journal-title":"Eurosurveillance"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1007\/s10900-019-00768-w","article-title":"Missed Opportunities for Hepatitis A Vaccination Among MSM Initiating PrEP","volume":"45","author":"Cohall","year":"2020","journal-title":"J. Community Health."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nicolay, N., Le Bourhis-Zaimi, M., Lesourd, A., Martel, M., Roque-Afonso, A.M., Erouart, S., Etienne, M., and Ndeikoundam Ngangro, N. (2020). A description of a hepatitis A outbreak in men who have sex with men and public health measures implemented in Seine-Maritime department, Normandy, France, 2017. BMC Public Health, 20.","DOI":"10.1186\/s12889-020-09499-3"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s00535-006-1888-9","article-title":"Molecular epidemiology of hepatitis A virus in metropolitan areas in Japan","volume":"41","author":"Takahashi","year":"2006","journal-title":"J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"89","DOI":"10.7883\/yoken.JJID.2019.275","article-title":"Comparison of the Clinical Features of Hepatitis A in People Living with HIV between Pandemics in 1999-2000 and 2017-2018 in the Metropolitan Area of Japan","volume":"73","author":"Koga","year":"2020","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s00535-012-0624-x","article-title":"Acute liver failure in Japan: Definition, classification, and prediction of the outcome","volume":"47","author":"Sugawara","year":"2012","journal-title":"J. Gastroenterol."},{"key":"ref_15","first-page":"36","article-title":"The case study of food born infection caused by hepatitis A virus in Tokyo","volume":"54","author":"Shinkai","year":"2003","journal-title":"Ann. Rep. Tokyo Metrop. Inst. Public Health"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jcv.2011.11.008","article-title":"Epidemiological and genetic analyses of a diffuse outbreak of hepatitis A in Japan, 2010","volume":"53","author":"Ishii","year":"2012","journal-title":"J. Clin. Virol."},{"key":"ref_17","first-page":"51","article-title":"Detection status and subtype classification of hepatitis A virus in Tokyo","volume":"70","author":"Asakura","year":"2019","journal-title":"Ann. Rep. Tokyo Metrop. Inst. Public Health"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kanda, T., Jeong, S.H., Imazeki, F., Fujiwara, K., and Yokosuka, O. (2010). Analysis of 5\u2032 nontranslated region of hepatitis A viral RNA genotype I from South Korea: Comparison with disease severities. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015139"},{"key":"ref_19","unstructured":"National Institute of Infectious Diseases (2020, June 12). Infectious Disease Surveillance Center. (In Japanese)."},{"key":"ref_20","unstructured":"Iorio, N., and John, S. (2020). Hepatitis A. StatPearls."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1002\/jmv.21822","article-title":"Atypical manifestations of hepatitis A infection: A prospective, multicenter study in Korea","volume":"82","author":"Jung","year":"2010","journal-title":"J. Med. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1111\/j.1872-034X.2012.00988.x","article-title":"Hepatitis A outbreak associated with a revolving sushi bar in Chiba, Japan: Application of molecular epidemiology","volume":"42","author":"Tominaga","year":"2012","journal-title":"Hepatol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e26","DOI":"10.1097\/OLQ.0000000000000937","article-title":"Hepatitis A Outbreak Among Men Who Have Sex With Men, Yokohama, Japan, January to May 2018","volume":"46","author":"Yoshimura","year":"2019","journal-title":"Sex Transm. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1111\/hepr.13314","article-title":"Outbreak of hepatitis A linked to European outbreaks among men who have sex with men in Osaka, Japan, from March to July 2018","volume":"49","author":"Tanaka","year":"2019","journal-title":"Hepatol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1111\/jgh.14655","article-title":"Characteristics of acute hepatitis A virus infection before and after 2001: A hospital-based study in Tokyo, Japan","volume":"34","author":"Kogiso","year":"2019","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.bbrc.2005.03.212","article-title":"Amantadine inhibits hepatitis A virus internal ribosomal entry site-mediated translation in human hepatoma cells","volume":"331","author":"Kanda","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5599","DOI":"10.1128\/JVI.01773-05","article-title":"Silencing of hepatitis A virus infection by small interfering RNAs","volume":"80","author":"Kusov","year":"2006","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.7150\/ijms.27489","article-title":"Inhibitory effect of Japanese rice-koji miso extracts on hepatitis A virus replication in association with the elevation of glucose-regulated protein 78 expression","volume":"15","author":"Win","year":"2018","journal-title":"Int. J. Med. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.21873\/invivo.12168","article-title":"Additive Effects of Zinc Chloride on the Suppression of Hepatitis A Virus Replication by Interferon in Human Hepatoma Huh7 Cells","volume":"34","author":"Kanda","year":"2020","journal-title":"In Vivo"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/2\/207\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:17:22Z","timestamp":1760159842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/2\/207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,29]]},"references-count":29,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["v13020207"],"URL":"https:\/\/doi.org\/10.3390\/v13020207","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,29]]}}}