{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:51:09Z","timestamp":1791899469507,"version":"4.3.4"},"reference-count":75,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis D virus (HDV) is a small, defective RNA virus that depends on hepatitis B virus (HBV) for virion assembly and transmission. It replicates within the nucleus of hepatocytes and interacts with several cellular proteins. Chronic hepatitis D is a severe and progressive disease, leading to cirrhosis in up to 80% of cases. A high proportion of patients die of liver decompensation or hepatocellular carcinoma (HCC), but the lack of large prospective studies has made it difficult to precisely define the rate of these long-term complications. In particular, the question of whether HDV is an oncogenic virus has been a matter of debate. Studies conducted over the past decade provided evidence that HDV is associated with a significantly higher risk of developing HCC compared to HBV monoinfection. However, the mechanisms whereby HDV promotes liver cancer remain elusive. Recent data have demonstrated that the molecular profile of HCC-HDV is unique and distinct from that of HBV-HCC, with an enrichment of upregulated genes involved in cell-cycle\/DNA replication, and DNA damage and repair, which point to genome instability as an important mechanism of HDV hepatocarcinogenesis. These data suggest that HBV and HDV promote carcinogenesis by distinct molecular mechanisms despite the obligatory dependence of HDV on HBV.<\/jats:p>","DOI":"10.3390\/v13050830","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T22:51:42Z","timestamp":1620255102000},"page":"830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Hepatitis D Virus and Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Patrizia","family":"Farci","sequence":"first","affiliation":[{"name":"Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6169-9586","authenticated-orcid":false,"given":"Grazia Anna","family":"Niro","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Fondazione IRCCS \u201cCasa Sollievo Sofferenza\u201d, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Zamboni","sequence":"additional","affiliation":[{"name":"Liver Transplantation Center, Azienda Ospedaliera Brotzu, 09134 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1214-2383","authenticated-orcid":false,"given":"Giacomo","family":"Diaz","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche, Universit\u00e0 di Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1053\/j.gastro.2018.08.065","article-title":"Epidemiology and Management of Hepatocellular Carcinoma","volume":"156","author":"Kulik","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1159\/000367754","article-title":"Tumor Heterogeneity in Hepatocellular Carcinoma: Facing the Challenges","volume":"5","author":"Lu","year":"2016","journal-title":"Liver Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1002\/cncr.29936","article-title":"Annual Report to the Nation on the Status of Cancer, 1975\u20132012, featuring the increasing incidence of liver cancer","volume":"122","author":"Ryerson","year":"2016","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"James","year":"2018","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/hep.1840030518","article-title":"The delta agent","volume":"3","author":"Rizzetto","year":"1983","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1055\/s-0032-1323628","article-title":"Clinical features of hepatitis D","volume":"32","author":"Farci","year":"2012","journal-title":"Semin. 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