{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:23:20Z","timestamp":1790393000591,"version":"4.1.0"},"reference-count":225,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T00:00:00Z","timestamp":1552867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Almost all patients with hepatocellular carcinoma (HCC), a major type of primary liver cancer, also have liver cirrhosis, the severity of which hampers effective treatment for HCC despite recent progress in the efficacy of anticancer drugs for advanced stages of HCC. Here, we review recent knowledge concerning the molecular mechanisms of liver cirrhosis and its progression to HCC from genetic and epigenomic points of view. Because ~70% of patients with HCC have hepatitis B virus (HBV) and\/or hepatitis C virus (HCV) infection, we focused on HBV- and HCV-associated HCC. The literature suggests that genetic and epigenetic factors, such as microRNAs, play a role in liver cirrhosis and its progression to HCC, and that HBV- and HCV-encoded proteins appear to be involved in hepatocarcinogenesis. Further studies are needed to elucidate the mechanisms, including immune checkpoints and molecular targets of kinase inhibitors, associated with liver cirrhosis and its progression to HCC.<\/jats:p>","DOI":"10.3390\/ijms20061358","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T12:18:53Z","timestamp":1552911533000},"page":"1358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":235,"title":["Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-5090","authenticated-orcid":false,"given":"Tatsuo","family":"Kanda","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2560-3639","authenticated-orcid":false,"given":"Taichiro","family":"Goto","sequence":"additional","affiliation":[{"name":"Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu, Yamanashi 400-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-834X","authenticated-orcid":false,"given":"Yosuke","family":"Hirotsu","sequence":"additional","affiliation":[{"name":"Genome Analysis Center, Yamanashi Central Hospital, Yamanashi 400-8506, 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, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Omata","sequence":"additional","affiliation":[{"name":"Genome Analysis Center, Yamanashi Central Hospital, Yamanashi 400-8506, Japan"},{"name":"The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1002\/hep.1840210308","article-title":"Incidence of hepatocellular carcinoma in chronic hepatitis B and C: A prospective study of 251 patients","volume":"21","author":"Takano","year":"1995","journal-title":"Hepatology"},{"key":"ref_2","first-page":"20","article-title":"Segmental liver resections, present and future-caudate lobe resection for liver tumours","volume":"45","author":"Takayama","year":"1998","journal-title":"Hepatogastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N. 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