{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:12:51Z","timestamp":1789906371064,"version":"4.0.1"},"reference-count":200,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T00:00:00Z","timestamp":1538092800000},"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>Despite the success of direct-acting antiviral (DAA) agents in treating chronic hepatitis C virus (HCV) infection, the number of cases of HCV-related hepatocellular carcinoma (HCC) is expected to increase over the next five years. HCC develops over the span of decades and is closely associated with fibrosis stage. HCV both directly and indirectly establishes a pro-inflammatory environment favorable for viral replication. Repeated cycles of cell death and regeneration lead to genomic instability and loss of cell cycle control. DAA therapy offers &gt;90% sustained virological response (SVR) rates with fewer side effects and restrictions than interferon. While elimination of HCV helps to restore liver function and reverse mild fibrosis, post-SVR patients remain at elevated risk of HCC. A series of studies reporting higher than expected rates of HCC development among DAA-treated patients ignited debate over whether use of DAAs elevates HCC risk compared to interferon. However, recent prospective and retrospective studies based on larger patient cohorts have found no significant difference in risk between DAA and interferon therapy once other factors are taken into account. Although many mechanisms and pathways involved in hepatocarcinogenesis have been elucidated, our understanding of drivers specific to post-SVR hepatocarcinogenesis is still limited, and lack of suitable in vivo and in vitro experimental systems has hampered efforts to examine etiology-specific mechanisms that might serve to answer this question more thoroughly. Further research is needed to identify risk factors and biomarkers for post-SVR HCC and to develop targeted therapies based on more complete understanding of the molecules and pathways implicated in hepatocarcinogenesis.<\/jats:p>","DOI":"10.3390\/v10100531","type":"journal-article","created":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T13:37:58Z","timestamp":1538141878000},"page":"531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Molecular Mechanisms of Hepatocarcinogenesis Following Sustained Virological Response in Patients with Chronic Hepatitis C Virus Infection"],"prefix":"10.3390","volume":"10","author":[{"given":"C. Nelson","family":"Hayes","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Metabolism, Graduate School of Biomedical &amp; Health Sciences, Applied Life Sciences, Institute of Biomedical &amp; Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan"},{"name":"Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabolism, Graduate School of Biomedical &amp; Health Sciences, Applied Life Sciences, Institute of Biomedical &amp; Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan"},{"name":"Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima 734-8551, Japan"},{"name":"Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Chayama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabolism, Graduate School of Biomedical &amp; Health Sciences, Applied Life Sciences, Institute of Biomedical &amp; Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan"},{"name":"Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima 734-8551, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1200\/JCO.2005.05.2308","article-title":"Patterns of cancer incidence, mortality, and prevalence across five continents: Defining priorities to reduce cancer disparities in different geographic regions of the world","volume":"24","author":"Kamangar","year":"2006","journal-title":"J. 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