{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:47:49Z","timestamp":1788918469757,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development (AMED)","doi-asserted-by":"publisher","award":["JP24fk0210132"],"award-info":[{"award-number":["JP24fk0210132"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development (AMED)","doi-asserted-by":"publisher","award":["JP25fk0210132"],"award-info":[{"award-number":["JP25fk0210132"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development (AMED)","doi-asserted-by":"publisher","award":["JP23K15055"],"award-info":[{"award-number":["JP23K15055"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["JP24fk0210132"],"award-info":[{"award-number":["JP24fk0210132"]}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["JP25fk0210132"],"award-info":[{"award-number":["JP25fk0210132"]}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["JP23K15055"],"award-info":[{"award-number":["JP23K15055"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Hepatitis A virus (HAV) infection sometimes results in the occurrence of acute liver failure and acute-on-chronic liver failure (ACLF), which is often fatal, especially in patients with diabetes mellitus or elderly individuals. ACLF is observed in patients with cirrhosis who occasionally have zinc deficiency. However, effective drugs for hepatitis A are currently unavailable. Glucose-regulated protein 78 (GRP78) is an antiviral agent that has been reported to prevent HAV replication. The effects of zinc acetate on HAV HA11-1299 genotype IIIA replication and changes in GRP78 levels in human hepatocytes with or without HAV infection were examined. Zinc acetate inhibited HAV HA11-1299 genotype IIIA replication in both Huh7 and GL37 cells. Zinc acetate also inhibited HAV replication in both low- and high-glucose media. Zinc acetate increased the expression of GRP78, in response to HAV replication. The combination of zinc acetate with ribavirin led to greater suppression of both HAV HA11-1299 genotype IIIA and HAV HM175\/18f genotype IB replication in Huh7 cells than that of ribavirin alone. In conclusion, zinc acetate inhibits HAV replication in accompany with the elevation of GRP78 expression without causing cellular toxicity. Zinc compounds may be useful for the treatment of ACLF caused by HAV infection.<\/jats:p>","DOI":"10.3390\/pathogens14090882","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T09:18:57Z","timestamp":1756977537000},"page":"882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Zinc Acetate Inhibits Hepatitis A Virus Replication: Possible Treatment for Patients with Type A Acute-on-Chronic Liver Failure"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8135-342X","authenticated-orcid":false,"given":"Tatsuo","family":"Kanda","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Uonuma Kikan Hospital, 4132 Urasa, Minami-Uonuma 949-7302, Japan"},{"name":"Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Aasahimachi-Dori, Chuo-ku, Niigata 951-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Sasaki-Tanaka","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Aasahimachi-Dori, Chuo-ku, Niigata 951-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2618-7494","authenticated-orcid":false,"given":"Hiroyuki","family":"Abe","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Aasahimachi-Dori, Chuo-ku, Niigata 951-8520, 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Dental Sciences, Niigata University, 1-757 Aasahimachi-Dori, Chuo-ku, Niigata 951-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9135-3092","authenticated-orcid":false,"given":"Hiroteru","family":"Kamimura","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Aasahimachi-Dori, Chuo-ku, Niigata 951-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsunori","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Yamanashi, Chuo 409-3898, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5118-4397","authenticated-orcid":false,"given":"Ryota","family":"Masuzaki","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and 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