Identification of hepatitis B virus integration in hepatitis C virus-infected hepatocellular carcinoma tissues

• Published in: Journal of hepatology 1997-04, Vol.26 (4), p.771-778
• Main Authors: Urashima, Tetsuro, Saigo, Kenichi, Kobayashi, Susumu, Imaseki, Hideo, Matsubara, Hisahiro, Koide, Yoshio, Asano, Takehide, Kondo, Yoichiro, Koike, Katsuro, Isono, Kaichi
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Blotting, Southern; Carcinoma, Hepatocellular - virology; DNA, Viral - analysis; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hepacivirus - genetics; Hepatitis Antibodies - analysis; Hepatitis B Surface Antigens - analysis; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - immunology; Hepatitis C - genetics; Hepatitis C - immunology; Hepatitis C virus; Hepatocellular carcinoma; Human viral diseases; Humans; Infectious diseases; Integration of HBV DNA; Liver Neoplasms - virology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Polymerase Chain Reaction; RNA, Messenger - analysis; RNA, Viral - analysis; Transcription, Genetic; Tumors; Viral diseases; Viral hepatitis; Virus Integration; X region
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(97)80241-3

Background/Aims: 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 sero-negative 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.