Differential integration rates of hepatitis B virus DNA in the liver of children with chronic hepatitis B virus infection and hepatocellular carcinoma.
OBJECTIVE
Integration of hepatitis B virus-DNA (HBV-DNA) into the host genome, a phenomenon found frequently in hepatocellular carcinomas (HCC) and causally linked to oncogenesis, has not been well characterized in children. The aim of the present study was to determine the prevalence of HBV integration more accurately and to decide whether the integration rate varies at different stages of chronic HBV infection in children.


METHODS
Of 13 children with chronic hepatitis, 14 liver biopsy tissues were analyzed. One liver tissue with pure liver cirrhosis, nine non-tumor, and nine tumor liver tissues from children with HCC were analyzed by a very sensitive method, inverse polymerase chain reaction (IPCR).


RESULTS
Thirteen genuine viral-host junctional sequences from 23 patients were successfully isolated and proved that IPCR is a useful method in this context. The results also indicated that the detection rate of HBV-DNA integration increased in parallel with the progress of liver histology towards the neoplastic transformation, with 0% in the liver of chronic hepatitis, 22.2% in non-tumor livers of HCC patients, and 66.7% in tumor liver tissues of HCC patients.


CONCLUSIONS
The present results indicate that integration of HBV-DNA into the host genome was rarely confirmed at the early stage of chronic hepatitis in children until the stage of HCC formation.
Huang
Hsiang-Po
HP
Department of Pediatrics, College of Medicine, National Taiwan University, 10016 Taipei, Taiwan.
Tsuei
Daw-Jen
DJ
Wang
Kuan-Jan
KJ
Chen
Ying-Lien
YL
Ni
Yen-Hsuan
YH
Jeng
Yung-Ming
YM
Chen
Huey-Ling
HL
Hsu
Hong-Yuan
HY
Chang
Mei-Hwei
MH
D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics / Q000821:virology*; D002648:Child; D004262:DNA Restriction Enzymes; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000821:virology*; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics / Q000821:virology*; D008297:Male; D016133:Polymerase Chain Reaction; D016662:Virus Integration
D004279:DNA, Viral; D004262:DNA Restriction Enzymes