Impact of hepatitis B virus (HBV) X gene integration in liver tissue on hepatocellular carcinoma development in serologically HBV-negative chronic hepatitis C patients.
OBJECTIVE
We analyzed hepatitis B virus (HBV) X gene integration in hepatocytes of HBV-negative, chronic hepatitis C (CH-C) patients with mild fibrosis, and prospectively followed these patients for the development of hepatocellular carcinoma (HCC).


METHODS
The study included 39 HBV-negative CH-C patients with mild fibrosis. HBV-X integration was determined by Alu-PCR analysis of liver specimens obtained by fine-needle biopsy.


RESULTS
Integration of HBV-X gene sequence into liver genome occurred in 9 of the 39 patients. Six of the 39 patients developed HCC during the 12-year follow-up period. No significant difference was found in the incidence of HCC between patients with and without HBV-X integration. However, the two patients with HBV-X integration who developed HCC did not have cirrhosis at the time when HCC was diagnosed, whereas the four patients without HBV-X integration who developed HCC did have cirrhosis.


CONCLUSIONS
Our findings suggest that HBV-X integration detected at the mild fibrosis stage might not indicate a high risk for HCC. HBV-X integration may be associated with HCC development in the absence of cirrhosis. However, we did not find evidence that HBV-X integration directly plays a role in hepatocarcinogenesis in CH-C patients. Further studies will be needed to clarify this point.
Toyoda
Hidenori
H
Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan.
Kumada
Takashi
T
Kaneoka
Yuji
Y
Murakami
Yoshiki
Y
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000821:virology*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D016679:Genome, Viral; D006515:Hepatitis B virus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000473:pathology* / Q000821:virology*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology; D008113:Liver Neoplasms / Q000473:pathology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics*; D016662:Virus Integration / Q000235:genetics*
D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D004247:DNA