title: Identification of hepatitis B virus integration in hepatitis C virus-infected hepatocellular carcinoma tissues.
abstract: OBJECTIVE
  The integration of HBV DNA is thought to be involved in the initial stage of hepatocarcinogenesis, and it has been reported that transactivating factors encoded by the X and preS2/S genes stimulate transcription of multiple viral and cellular genes. We assessed the possible contributions of hepatitis B virus integration to the occurrence of hepatocellular carcinoma in hepatitis C virus-infected as well as in hepatitis B virus-infected patients by identifying the integrated HBV DNA sequence, and the X and preS2/S regions were further investigated in HBV DNA-integrated cases.
  
  
  METHODS
  Southern blot hybridization for detecting HBV DNA in tumor tissues from 28 hepatocellular carcinoma patients was carried out with full-length HBV DNA, and then with X and preS2/S regions as probes. We also carried out reverse transcription-polymerase chain reaction for detecting HCV RNA to confirm hepatitis C virus-infection in liver tissues.
  
  
  RESULTS
  Clonally integrated HBV DNA sequences were demonstrated in 16 of 28 patients (57.1%), including five HBsAg seropositive and 11 HBsAg seronegative patients. Of these 11 HBsAg seronegative patients, 10 were also positive for anti-HCV in their sera, and all nine examined cases had HCV RNA in liver. Furthermore, the X region was identified in 14 of 16 HBV DNA integrated cases (87.5%), and the preS2/S region in 6/16 (37.5%).
  
  
  CONCLUSIONS
  The present Southern blot analysis demonstrates that clonally integrated HBV DNA sequences were identified even in hepatitis C virus-infected hepatocellular carcinoma patients at a high rate (10/18, 55.6%), and suggests that integrated hepatitis B virus, whose major component is the X gene, may play an important role in hepatocarcinogenesis in hepatitis B virus-integrated cases with and without hepatitis C virus infection.
authors.affiliation: Second Department of Surgery, Chiba University School of Medicine, Chuo-ku, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Urashima
authors.forename: K
authors.initials: K
authors.lastname: Saigo
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Imaseki
authors.forename: H
authors.initials: H
authors.lastname: Matsubara
authors.forename: Y
authors.initials: Y
authors.lastname: Koide
authors.forename: T
authors.initials: T
authors.lastname: Asano
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.forename: K
authors.initials: K
authors.lastname: Isono
mesh_terms: D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D016174:Hepacivirus / Q000235:genetics*; D006508:Hepatitis Antibodies / Q000032:analysis; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D006526:Hepatitis C / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D014158:Transcription, Genetic; D016662:Virus Integration
chemical_list: D004279:DNA, Viral; D006508:Hepatitis Antibodies; D006514:Hepatitis B Surface Antigens; D012333:RNA, Messenger; D012367:RNA, Viral