title: Genetic basis of hepatitis virus-associated hepatocellular carcinoma: linkage between infection, inflammation, and tumorigenesis.
abstract: Hepatitis virus infection is a leading cause of chronic liver disease, including cirrhosis and hepatocellular carcinoma (HCC). Although anti-viral therapies against hepatitis B virus (HBV) and hepatitis C virus (HCV) have dramatically progressed during the past decade, the estimated number of people chronically infected with HBV and/or HCV is ~370 million, and hepatitis virus-associated hepatocarcinogenesis is a serious health concern worldwide. Understanding the mechanism of virus-associated carcinogenesis is crucial toward both treatment and prevention, and the recently developed whole genome/exome sequencing analysis using next-generation sequencing technologies has contributed to unveiling the landscape of genetic and epigenetic aberrations in not only tumor tissues but also the background liver tissues underlying chronic liver damage caused by hepatitis virus infection. Several major mechanisms underlie the genetic and epigenetic aberrations in the hepatitis virus-infected liver, such as the generation of reactive oxidative stress, ectopic expression of DNA mutator enzymes, and dysfunction of the DNA repair system. In addition, direct oncogenic effects of hepatitis virus, represented by the integration of HBV-DNA, are observed in infected hepatocytes. Elucidating the whole picture of genetic and epigenetic alterations, as well as the mechanisms of tumorigenesis, will facilitate the development of efficient treatment and prevention strategies for hepatitis virus-associated HCC.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takai
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Inuzuka
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. maru@kuhp.kyoto-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Marusawa
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology* / Q000821:virology; D004260:DNA Repair; D044127:Epigenesis, Genetic; D006509:Hepatitis B / Q000150:complications* / Q000188:drug therapy; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology
chemical_list: D000998:Antiviral Agents
keywords: Cirrhosis; Hepatocarcinogenesis; Inflammation; Next-generation sequencing; Whole genome sequencing