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Comparison of complete sequences of hepatitis B virus genotype C between inactive carriers and hepatocellular carcinoma patients before and after seroconversion

  • Liver, Pancreas, and Biliary Tract
  • Published:
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Abstract

Background

Most patients who acquire chronic hepatitis B virus (HBV) infection by perinatal transmission become inactive carriers (IC) after hepatitis B e (HBe) antigen seroconversion, whereas some patients have persistent abnormal serum transaminase levels and develop hepatocellular carcinoma (HCC) in the anti-HBe-positive phase. The aim of this study was to investigate the HCC-related mutations of HBV.

Methods

Complete sequences of HBV were examined among eight IC and eight HCC patients infected with HBV genotype C before and after seroconversion.

Results

The frequency of the T1653 mutation tended to be higher among HCC patients after seroconversion (16.7% vs. 62.5%; P = 0.086). The prevalence of a basal core promoter double mutation (T1762/A1764) was high among both IC and HCC patients after seroconversion (83.3% vs. 87.5%; P = 0.825). Among the HCC patients, a pre-S deletion mutant was detected in 62.5% patients before seroconversion, and in 37.5% patients after seroconversion. The core deletion mutant was also detected in 50% of HCC patients only before seroconversion. Deletion mutants of the pre-S or core region before seroconversion were significantly associated with HCC patients (0% vs. 62.5%; P = 0.007, 0% vs. 50%; P = 0.021, respectively).

Conclusions

Our data showed a significant association of pre-S and core deletion mutants before seroconversion with HCC development. The T1653 mutation after seroconversion was frequently found in HCC patients infected with HBV genotype C. These results suggest that mutations may be predictive factor for development of HCC.

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References

  1. DM Parkin (2004) ArticleTitleInternational variation Oncogene 23 6329–40 Occurrence Handle15322508 Occurrence Handle10.1038/sj.onc.1207726 Occurrence Handle1:CAS:528:DC%2BD2cXmvVOrtLY%3D

    Article  PubMed  CAS  Google Scholar 

  2. NV Naoumov R Schneider T Grotzinger MC Jung S Miska GR Pape et al. (1992) ArticleTitlePrecore mutant hepatitis B virus infection and liver disease Gastroenterology 102 538–43 Occurrence Handle1732124 Occurrence Handle1:STN:280:By2C38%2FjvVc%3D

    PubMed  CAS  Google Scholar 

  3. F Sugauchi T Ohno E Orito H Sakugawa T Ichida M Komatsu et al. (2003) ArticleTitleInfluence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease J Med Virol 70 537–44 Occurrence Handle12794715 Occurrence Handle10.1002/jmv.10428 Occurrence Handle1:CAS:528:DC%2BD3sXlslOmsLY%3D

    Article  PubMed  CAS  Google Scholar 

  4. YF Fan CC Lu WC Chen WJ Yao HC Wang TT Chang et al. (2001) ArticleTitlePrevalence and significance of hepatitis B virus (HBV) pre-S mutants in serum and liver at different replicative stages of chronic HBV infection Hepatology 33 277–86 Occurrence Handle11124846 Occurrence Handle10.1053/jhep.2001.21163 Occurrence Handle1:STN:280:DC%2BD3M%2FpvFSjuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  5. TT Huy H Ushijima KM Win P Luengrojanakul PK Shrestha ZH Zhong et al. (2003) ArticleTitleHigh prevalence of hepatitis B virus pre-s mutant in countries where it is endemic and its relationship with genotype and chronicity J Clin Microbiol 41 5449–55 Occurrence Handle14662924 Occurrence Handle10.1128/JCM.41.12.5449-5455.2003 Occurrence Handle1:CAS:528:DC%2BD2cXjtFyqtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  6. JH Kao PJ Chen MY Lai DS Chen (2003) ArticleTitleBasal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers Gastroenterology 124 327–34 Occurrence Handle12557138 Occurrence Handle10.1053/gast.2003.50053 Occurrence Handle1:CAS:528:DC%2BD3sXhsFOhtbk%3D

    Article  PubMed  CAS  Google Scholar 

  7. BF Chen CJ Liu GM Jow PJ Chen JH Kao DS Chen (2006) ArticleTitleHigh prevalence and mapping of pre-S deletion in hepatitis B virus carriers with progressive liver diseases Gastroenterology 130 1153–68 Occurrence Handle16618410 Occurrence Handle10.1053/j.gastro.2006.01.011 Occurrence Handle1:CAS:528:DC%2BD28XksFWmurY%3D

    Article  PubMed  CAS  Google Scholar 

  8. S Marschenz AS Endres A Brinckmann T Heise G Kristiansen P Nurnberg et al. (2006) ArticleTitleFunctional analysis of complex hepatitis B virus variants associated with development of liver cirrhosis Gastroenterology 131 765–80 Occurrence Handle16952546 Occurrence Handle10.1053/j.gastro.2006.07.008 Occurrence Handle1:CAS:528:DC%2BD28XhtVKrurjE

    Article  PubMed  CAS  Google Scholar 

  9. P Preikschat S Gunther S Reinhold H Will K Budde HH Neumayer et al. (2002) ArticleTitleComplex HBV populations with mutations in core promoter, C gene, and pre-S region are associated with development of cirrhosis in long-term renal transplant recipients Hepatology 35 466–77 Occurrence Handle11826424 Occurrence Handle10.1053/jhep.2002.30698 Occurrence Handle1:CAS:528:DC%2BD38XhsVGrt7Y%3D

    Article  PubMed  CAS  Google Scholar 

  10. C Ferrari A Cavalli A Penna A Valli A Bertoletti G Pedretti et al. (1992) ArticleTitleFine specificity of the human T-cell response to the hepatitis B virus preS1 antigen Gastroenterology 103 255–63 Occurrence Handle1377142 Occurrence Handle1:CAS:528:DyaK38Xlt12msrg%3D

    PubMed  CAS  Google Scholar 

  11. K Kuroki M Floreani LT Mimms D Ganem (1990) ArticleTitleEpitope mapping of the PreS1 domain of the hepatitis B virus large surface protein Virology 176 620–4 Occurrence Handle1693249 Occurrence Handle10.1016/0042-6822(90)90032-M Occurrence Handle1:CAS:528:DyaK3cXktlymsbY%3D

    Article  PubMed  CAS  Google Scholar 

  12. DR Milich A McLachlan A Moriarty GB Thornton (1987) ArticleTitleImmune response to hepatitis B virus core antigen (HBcAg): localization of T cell recognition sites within HBcAg/HBeAg J Immunol 139 1223–31 Occurrence Handle2440947 Occurrence Handle1:CAS:528:DyaL2sXmtlCgtL8%3D

    PubMed  CAS  Google Scholar 

  13. M Mizokami T Nakano E Orito Y Tanaka H Sakugawa M Mukaide et al. (1999) ArticleTitleHepatitis B virus genotype assignment using restriction fragment length polymorphism patterns FEBS Lett 450 66–71 Occurrence Handle10350059 Occurrence Handle10.1016/S0014-5793(99)00471-8 Occurrence Handle1:CAS:528:DyaK1MXivFegsbg%3D

    Article  PubMed  CAS  Google Scholar 

  14. S Usuda H Okamoto T Tanaka K Kidd-Ljunggren PV Holland Y Miyakawa et al. (2000) ArticleTitleDifferentiation of hepatitis B virus genotypes D and E by ELISA using monoclonal antibodies to epitopes on the preS2-region product J Virol Methods 87 81–9 Occurrence Handle10856755 Occurrence Handle10.1016/S0166-0934(00)00153-1 Occurrence Handle1:CAS:528:DC%2BD3cXktVSnsL8%3D

    Article  PubMed  CAS  Google Scholar 

  15. F Sugauchi M Mizokami E Orito T Ohno H Kato S Suzuki et al. (2001) ArticleTitleA novel variant genotype C of hepatitis B virus identified in isolates from Australian Aborigines: complete genome sequence and phylogenetic relatedness J Gen Virol 82 883–92 Occurrence Handle11257194 Occurrence Handle1:CAS:528:DC%2BD3MXisFWms7Y%3D

    PubMed  CAS  Google Scholar 

  16. CL Lin LY Liao CS Wang PJ Chen MY Lai DS Chen et al. (2005) ArticleTitleBasal core-promoter mutant of hepatitis B virus and progression of liver disease in hepatitis B e antigen-negative chronic hepatitis B Liver Int 25 564–70 Occurrence Handle15910494 Occurrence Handle10.1111/j.1478-3231.2005.01041.x

    Article  PubMed  Google Scholar 

  17. CJ Chu EB Keeffe SH Han RP Perrillo AD Min C Soldevila-Pico et al. (2003) ArticleTitlePrevalence of HBV precore/core promoter variants in the United States Hepatology 38 619–28 Occurrence Handle12939588 Occurrence Handle10.1053/jhep.2003.50352 Occurrence Handle1:CAS:528:DC%2BD3sXnvVKjtrY%3D

    Article  PubMed  CAS  Google Scholar 

  18. Y Kajiya K Hamasaki K Nakata Y Nakagawa S Miyazoe Y Takeda et al. (2002) ArticleTitleFull-length sequence and functional analysis of hepatitis B virus genome in a virus carrier: a case report suggesting the impact of pre-S and core promoter mutations on the progression of the disease J Viral Hepat 9 149–56 Occurrence Handle11876799 Occurrence Handle10.1046/j.1365-2893.2002.00335.x Occurrence Handle1:STN:280:DC%2BD387ksFKiuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  19. CM Chu CT Yeh CS Lee IS Sheen YF Liaw (2002) ArticleTitlePrecore stop mutant in HBeAg-positive patients with chronic hepatitis B: clinical characteristics and correlation with the course of HBeAg-to-anti-HBe seroconversion J Clin Microbiol 40 16–21 Occurrence Handle11773086 Occurrence Handle10.1128/JCM.40.1.16-21.2002

    Article  PubMed  Google Scholar 

  20. K Ito Y Tanaka E Orito M Sugiyama K Fujiwara F Sugauchi et al. (2006) ArticleTitleT1653 mutation in the box alpha increases the risk of hepatocellular carcinoma in patients with chronic hepatitis B virus genotype C infection Clin Infect Dis 42 1–7 Occurrence Handle16323084 Occurrence Handle10.1086/498522 Occurrence Handle1:CAS:528:DC%2BD28XmsVanug%3D%3D

    Article  PubMed  CAS  Google Scholar 

  21. CY Maeng CJ Ryu P Gripon C Guguen-Guillouzo HJ Hong (2000) ArticleTitleFine mapping of virus-neutralizing epitopes on hepatitis B virus PreS1 Virology 270 9–16 Occurrence Handle10772975 Occurrence Handle10.1006/viro.2000.0250 Occurrence Handle1:CAS:528:DC%2BD3cXisFers7o%3D

    Article  PubMed  CAS  Google Scholar 

  22. A Penna A Bertoletti A Cavalli A Valli G Missale M Pilli et al. (1992) ArticleTitleFine specificity of the human T cell response to hepatitis B virus core antigen Arch Virol Suppl 4 23–8 Occurrence Handle1280506 Occurrence Handle1:STN:280:ByyD1c3hsV0%3D

    PubMed  CAS  Google Scholar 

  23. JH Park EW Cho YJ Lee SY Shin KL Kim (2000) ArticleTitleDetermination of the protective effects of neutralizing anti-hepatitis B virus (HBV) immunoglobulins by epitope mapping with recombinant HBV surface-antigen proteins Microbiol Immunol 44 703–10 Occurrence Handle11021401 Occurrence Handle1:CAS:528:DC%2BD3cXms1Ghs7w%3D

    PubMed  CAS  Google Scholar 

  24. MC Jung HM Diepolder U Spengler EA Wierenga R Zachoval RM Hoffmann et al. (1995) ArticleTitleActivation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection J Virol 69 3358–68 Occurrence Handle7538172 Occurrence Handle1:CAS:528:DyaK2MXls1yitr0%3D

    PubMed  CAS  Google Scholar 

  25. SL Tsai MH Chen CT Yeh CM Chu AN Lin FH Chiou et al. (1996) ArticleTitlePurification and characterization of a naturally processed hepatitis B virus peptide recognized by CD8+ cytotoxic T lymphocytes J Clin Invest 97 577–84 Occurrence Handle8567982 Occurrence Handle1:CAS:528:DyaK28Xht1Ols7o%3D Occurrence Handle10.1172/JCI118450

    Article  PubMed  CAS  Google Scholar 

  26. T Wakita S Kakumu M Shibata K Yoshioka Y Ito T Shinagawa et al. (1991) ArticleTitleDetection of pre-C and core region mutants of hepatitis B virus in chronic hepatitis B virus carriers J Clin Invest 88 1793–801 Occurrence Handle1752941 Occurrence Handle1:CAS:528:DyaK3sXjs1yktw%3D%3D

    PubMed  CAS  Google Scholar 

  27. US Akarca AS Lok (1995) ArticleTitleNaturally occurring core-gene-defective hepatitis B viruses J Gen Virol 76 IssueIDPt 7 1821–6 Occurrence Handle9049388 Occurrence Handle1:CAS:528:DyaK2MXmsl2lt7c%3D

    PubMed  CAS  Google Scholar 

  28. TT Yuan MH Lin SM Qiu C Shih (1998) ArticleTitleFunctional characterization of naturally occurring variants of human hepatitis B virus containing the core internal deletion mutation J Virol 72 2168–76 Occurrence Handle9499073 Occurrence Handle1:CAS:528:DyaK1cXhtFemtrs%3D

    PubMed  CAS  Google Scholar 

  29. PC Tai FM Suk WH Gerlich AR Neurath C Shih (2002) ArticleTitleHypermodification and immune escape of an internally deleted middle-envelope (M) protein of frequent and predominant hepatitis B virus variants Virology 292 44–58 Occurrence Handle11878907 Occurrence Handle10.1006/viro.2001.1239 Occurrence Handle1:CAS:528:DC%2BD38Xktl2gsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  30. K Yamamoto M Horikita F Tsuda K Itoh Y Akahane S Yotsumoto et al. (1994) ArticleTitleNaturally occurring escape mutants of hepatitis B virus with various mutations in the S gene in carriers seropositive for antibody to hepatitis B surface antigen J Virol 68 2671–6 Occurrence Handle8139044 Occurrence Handle1:CAS:528:DyaK2cXitFGhsrg%3D

    PubMed  CAS  Google Scholar 

  31. YH Hsieh IJ Su HC Wang WW Chang HY Lei MD Lai et al. (2004) ArticleTitlePre-S mutant surface antigens in chronic hepatitis B virus infection induce oxidative stress and DNA damage Carcinogenesis 25 2023–32 Occurrence Handle15180947 Occurrence Handle10.1093/carcin/bgh207 Occurrence Handle1:CAS:528:DC%2BD2cXnvVOqtL8%3D

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho, Mizuho-ku, Nagoya, 467-8601, Japan

    Kiyoaki Ito, Yasuhito Tanaka, Kei Fujiwara, Tomoyuki Sakamoto, Noboru Shinkai & Masashi Mizokami

  2. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Kiyoaki Ito, Kei Fujiwara, Fuminaka Sugauchi, Tomoyuki Sakamoto, Noboru Shinkai & Etsuro Orito

  3. National Hospital Organization Osaka National Hospital, Osaka, Japan

    Michio Kato

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  1. Kiyoaki Ito
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Ito, K., Tanaka, Y., Kato, M. et al. Comparison of complete sequences of hepatitis B virus genotype C between inactive carriers and hepatocellular carcinoma patients before and after seroconversion. J Gastroenterol 42, 837–844 (2007). https://doi.org/10.1007/s00535-007-2100-6

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  • DOI: https://doi.org/10.1007/s00535-007-2100-6

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