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

Abstract

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.

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  • Authors+Show Affiliations

    ,

    Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan.

    , ,

    Source

    Journal of hepatology 48:1 2008 Jan pg 43-50

    MeSH

    Adult
    Carcinoma, Hepatocellular
    DNA
    Female
    Genome, Viral
    Hepatitis B virus
    Hepatitis C, Chronic
    Humans
    Liver
    Liver Cirrhosis
    Liver Neoplasms
    Male
    Middle Aged
    Prospective Studies
    Reverse Transcriptase Polymerase Chain Reaction
    Trans-Activators
    Viral Regulatory and Accessory Proteins
    Virus Integration

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    18023912

    Citation

    Toyoda, Hidenori, et al. "Impact of Hepatitis B Virus (HBV) X Gene Integration in Liver Tissue On Hepatocellular Carcinoma Development in Serologically HBV-negative Chronic Hepatitis C Patients." Journal of Hepatology, vol. 48, no. 1, 2008, pp. 43-50.
    Toyoda H, Kumada T, Kaneoka Y, et al. Impact of hepatitis B virus (HBV) X gene integration in liver tissue on hepatocellular carcinoma development in serologically HBV-negative chronic hepatitis C patients. J Hepatol. 2008;48(1):43-50.
    Toyoda, H., Kumada, T., Kaneoka, Y., & Murakami, Y. (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. Journal of Hepatology, 48(1), pp. 43-50.
    Toyoda H, et al. Impact of Hepatitis B Virus (HBV) X Gene Integration in Liver Tissue On Hepatocellular Carcinoma Development in Serologically HBV-negative Chronic Hepatitis C Patients. J Hepatol. 2008;48(1):43-50. PubMed PMID: 18023912.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Impact of hepatitis B virus (HBV) X gene integration in liver tissue on hepatocellular carcinoma development in serologically HBV-negative chronic hepatitis C patients. AU - Toyoda,Hidenori, AU - Kumada,Takashi, AU - Kaneoka,Yuji, AU - Murakami,Yoshiki, Y1 - 2007/10/24/ PY - 2007/03/28/received PY - 2007/08/05/revised PY - 2007/08/08/accepted PY - 2007/11/21/pubmed PY - 2008/3/12/medline PY - 2007/11/21/entrez SP - 43 EP - 50 JF - Journal of hepatology JO - J. Hepatol. VL - 48 IS - 1 N2 - 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. SN - 0168-8278 UR - https://www.unboundmedicine.com/medline/citation/18023912/Impact_of_hepatitis_B_virus__HBV__X_gene_integration_in_liver_tissue_on_hepatocellular_carcinoma_development_in_serologically_HBV_negative_chronic_hepatitis_C_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0168-8278(07)00562-4 DB - PRIME DP - Unbound Medicine ER -