Impact of hepatitis B virus (HBV) X gene integration in liver tissue on hepatocellular carcinoma development in serologically HBV-negative chronic hepatitis C patients

Toyoda, Hidenori; Kumada, Takashi; Kaneoka, Yuji; Murakami, Yoshiki

doi:10.1016/j.jhep.2007.08.016

« Previous Next »Journal of Hepatology
Volume 48, Issue 1 , Pages 43-50, January 2008

Impact of hepatitis B virus (HBV) X gene integration in liver tissue on hepatocellular carcinoma development in serologically HBV-negative chronic hepatitis C patients☆

Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu 503-8502, Japan
Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu 503-8502, Japan
Yuji Kaneoka
- Department of Surgery, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu 503-8502, Japan
Yoshiki Murakami
- Laboratory of Human Tumor Virus, Institute for Viral Research, Kyoto University, Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
- Corresponding author. Tel.: +81 75 751 4034; fax: +81 75 751 3998.
- Present address: Unit of Human Disease Genomics, Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Yoshida-Konoe cho, Sakyo-ku, Kyoto 606-8501, Japan. Tel.: +81 75 753 9313; fax: +81 75 753 9314.

Received 28 March 2007; received in revised form 5 August 2007; accepted 8 August 2007. published online 24 October 2007.

Associate Editor: K. Koike

Background/Aims

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.

Keywords: HBV-X integration, Chronic hepatitis C, Hepatocellular carcinoma