IDENTIFICATION OF HEPATITIS-B VIRUS INTEGRATION IN HEPATITIS-C VIRUS-INFECTED HEPATOCELLULAR-CARCINOMA TISSUES

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 stimu late transcription of multiple viral and cellular genes, We assessed t he possible contributions of hepatitis B virus integration to the occu rrence of hepatocellular carcinoma in hepatitis C virus-infected as we b as in hepatitis B virus-infected patients by identifying the integra ted HBV DNA sequence, and the X and preS2/S regions were further inves tigated in HBV DNA-integrated cases. Methods: Southern blot hybridizat ion for detecting HBV DNA in tumor tissues from 28 hepatocellular carc inoma patients was carried out with full-length HBV DNA, and then with X and preS2/S regions as probes, We also carried out reverse transcri ption-polymerase chain reaction for detecting HCV RNA to confirm hepat itis C virus-infection in liver tissues. Results: Clonally integrated HBV DNA sequences were demonstrated in 16 of 28 patients (57.1%), incl uding five HBsAg seropositive and 11 HBsAg seronegative patients. Of t hese 11 HBsAg seronegative patients, 10 were also positive for anti-HC V in their sera, and all nine examined cases had HCV RNA in liver Furt hermore, the X region was identified in 14 of 16 HBV DNA integrated ca ses (87.5%), and the preS2/S region in 6/16 (37.5%), Conclusions: The present Southern blot analysis demonstrates that clonally integrated H BV DNA sequences were identified even in hepatitis C virus-infected he patocellular carcinoma patients at a high rate (10/18, 55.6%), and sug gests that integrated hepatitis B virus, whose major component is the X gene, may play an important role in hepatocarcino-genesis in hepatit is B virus-integrated cases with and without hepatitis C virus infecti on.