Skip to main content

Advertisement

SpringerLink
Log in

A weak association between occult HBV infection and non-B non-C hepatocellular carcinoma in Japan

  • Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

In Japan, approximately 10% of hepatocellular carcinoma (HCC) patients are negative for both hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV), i.e., they constitute the so-called category of non-B non-C (NBNC) HCC. Little is known about the characteristics of NBNC-HCC.

Methods

Potential risk factors for carcinogenesis (including occult HBV infection [HBsAg is negative but HBV DNA is positive by polymerase chain reaction (PCR)], obesity, and diabetes) were assessed in 233 HCC patients grouped according to hepatitis virus serological status (152 with HCV-HCC, 36 with HBV-HCC, and 45 with NBNC-HCC).

Results

The prevalence of patients with obesity or diabetes was significantly higher in the NBNC-HCC group than in the HBV-HCC group. The same trend was observed even when patients with massive alcohol intake were excluded from the analysis. Only 8 patients (18%) in the NBNC-HCC group had detectable serum HBV DNA, and this was at very low levels (HBV/Ce/C2 and HBV/D were determined in 7 and 1 patients, respectively). In the NBNC-HCC group, the determined nucleotide sequences of the enhancer II/core promoter/precore/core region did not contain any HCC-associated mutations, whereas 25 of 30 patients in the HBV-HCC group carried strains with C1653T, T1753V, and/or A1762T/G1764A mutations.

Conclusions

A weak association between occult HBV infection and HCC development was observed in the NBNC patients. This study indicates that nonalcoholic steato-hepatitis should be further investigated to assess its contribution to HCC development in this category of patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. ME Alpert MS Hutt GN Wogan CS Davidson (1971) ArticleTitleAssociation between aflatoxin content of food and hepatoma frequency in Uganda Cancer 28 253–60 Occurrence Handle4329335 Occurrence Handle10.1002/1097-0142(197107)28:1<253::AID-CNCR2820280151>3.0.CO;2-G Occurrence Handle1:STN:280:DyaE38%2FhsF2lsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  2. H Yotsuyanagi Y Shintani K Moriya H Fujie T Tsutsumi T Kato et al. (2000) ArticleTitleVirologic analysis of non-B, non-C hepatocellular carcinoma in Japan: frequent involvement of hepatitis B virus J Infect Dis 18 1920–8 Occurrence Handle10.1086/315512

    Article  Google Scholar 

  3. EE Powell WG Cooksley R Hanson J Searle JW Halliday LW Powell (1990) ArticleTitleThe natural history of nonalcoholic steatohepatitis: a follow-up study of 42 patients for up to 21 years Hepatology 11 74–80 Occurrence Handle2295475 Occurrence Handle10.1002/hep.1840110114

    Article  PubMed  Google Scholar 

  4. HP Cotrim R Parana E Braga L Lyra (2000) ArticleTitleNonalcoholic steatohepatitis and hepatocellular carcinoma: natural history? Am J Gastroenterol 95 3018–9 Occurrence Handle11051414 Occurrence Handle10.1111/j.1572-0241.2000.03241.x Occurrence Handle1:STN:280:DC%2BD3crgt12ksw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  5. Y Zen K Katayanagi K Tsuneyama K Harada I Araki Y Nakanuma (2001) ArticleTitleHepatocellular carcinoma arising in non-alcoholic steatohepatitis Pathol Int 51 127–31 Occurrence Handle11169153 Occurrence Handle10.1046/j.1440-1827.2001.01174.x Occurrence Handle1:STN:280:DC%2BD3M3hsVKitw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  6. H Kuper W Ye U Broome A Romelsjo LA Mucci A Ekbom et al. (2001) ArticleTitleThe risk of liver and bile duct cancer in patients with chronic viral hepatitis, alcoholism, or cirrhosis Hepatology 34 IssueID4 Pt 1 714–8 Occurrence Handle11584367 Occurrence Handle10.1053/jhep.2001.28233 Occurrence Handle1:STN:280:DC%2BD3Mrjs1Wjsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  7. TR Morgan S Mandayam MM Jamal (2004) ArticleTitleAlcohol and hepatocellular carcinoma Gastroenterology 127 IssueID5 Suppl 1 S87–96 Occurrence Handle15508108 Occurrence Handle10.1053/j.gastro.2004.09.020 Occurrence Handle1:CAS:528:DC%2BD2cXhtVGmtb%2FP

    Article  PubMed  CAS  Google Scholar 

  8. C Brechot V Thiers D Kremsdorf B Nalpas S Pol P Paterlini-Brechot (2001) ArticleTitlePersistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely “occult Hepatology 34 194–203 Occurrence Handle11431751 Occurrence Handle10.1053/jhep.2001.25172 Occurrence Handle1:STN:280:DC%2BD3MznsVKnuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  9. T Pollicino G Squadrito G Cerenzia I Cacciola G Raffa A Crax et al. (2004) ArticleTitleHepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection Gastroenterology 126 102–10 Occurrence Handle14699492 Occurrence Handle10.1053/j.gastro.2003.10.048 Occurrence Handle1:CAS:528:DC%2BD2cXhtFGntLs%3D

    Article  PubMed  CAS  Google Scholar 

  10. Hu KQ (2002) ArticleTitleOccult hepatitis B virus infection and its clinical implications J Viral Hepat 9 243–57 Occurrence Handle10.1046/j.1365-2893.2002.00344.x

    Article  Google Scholar 

  11. M Torbenson DL Thomas (2002) ArticleTitleOccult hepatitis B Lancet Infect Dis 2 479–86 Occurrence Handle12150847 Occurrence Handle10.1016/S1473-3099(02)00345-6

    Article  PubMed  Google Scholar 

  12. A Tamori S Nishiguchi S Kubo T Narimatsu D Habu T Takeda et al. (2003) ArticleTitleHBV DNA integration and HBV-transcript expression in non-B, non-C hepatocellular carcinoma in Japan J Med Virol 71 492–8 Occurrence Handle14556260 Occurrence Handle10.1002/jmv.10514 Occurrence Handle1:CAS:528:DC%2BD3sXptlCnu78%3D

    Article  PubMed  CAS  Google Scholar 

  13. R Kannangai E Molmenti L Arrazola A Klein M Choti DL Thomas et al. (2004) ArticleTitleOccult hepatitis B viral DNA in liver carcinomas from a region with a low prevalence of chronic hepatitis B infection J Viral Hepat 11 297–301 Occurrence Handle15230851 Occurrence Handle10.1111/j.1365-2893.2004.00502.x Occurrence Handle1:STN:280:DC%2BD2czjtVajuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  14. 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 

  15. T Kimura A Rokuhara Y Sakamoto S Yagi E Tanaka K Kiyosawa et al. (2002) ArticleTitleSensitive enzyme immunoassay for hepatitis B virus core-related antigens and their correlation to virus load J Clin Microbiol 40 439–45 Occurrence Handle11825954 Occurrence Handle10.1128/JCM.40.2.439-445.2002 Occurrence Handle1:CAS:528:DC%2BD38XhvFGktbk%3D

    Article  PubMed  CAS  Google Scholar 

  16. 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 IssueIDPt 4 883–92 Occurrence Handle11257194 Occurrence Handle1:CAS:528:DC%2BD3MXisFWms7Y%3D

    PubMed  CAS  Google Scholar 

  17. A Abe K Inoue T Tanaka J Kato N Kajiyama R Kawaguchi et al. (1999) ArticleTitleQuantitation of hepatitis B virus genomic DNA by real-time detection PCR J Clin Microbiol 37 2899–903 Occurrence Handle10449472 Occurrence Handle1:STN:280:DyaK1MzotVejsQ%3D%3D

    PubMed  CAS  Google Scholar 

  18. Y Tanaka I Hasegawa T Kato E Orito N Hirashima SK Acharya et al. (2004) ArticleTitleA case-control study for differences among hepatitis B virus infections of genotype A (subtypes Aa and Ae) and D Hepatology 40 747–55 Occurrence Handle15349915 Occurrence Handle10.1002/hep.20365

    Article  PubMed  Google Scholar 

  19. H Iizuka K Ohmura A Ishijima K Satoh T Tanaka F Tsuda et al. (1992) ArticleTitleCorrelation between anti-HBc titers and HBV DNA in blood units without detectable HBsAg Vox Sang 63 107–11 Occurrence Handle1441302 Occurrence Handle1:STN:280:DyaK3s%2FntVSkug%3D%3D Occurrence Handle10.1111/j.1423-0410.1992.tb02495.x

    Article  PubMed  CAS  Google Scholar 

  20. I Chemin C Trepo (2005) ArticleTitleClinical impact of occult HBV infections J Clin Virol 34 IssueIDSuppl 1 S15–21 Occurrence Handle16461218 Occurrence Handle10.1016/S1386-6532(05)80005-8

    Article  PubMed  Google Scholar 

  21. M Komori N Yuki T Nagaoka M Yamashiro K Mochizuki A Kaneko et al. (2001) ArticleTitleLong-term clinical impact of occult hepatitis B virus infection in chronic hepatitis B patients J Hepatol 35 798–804 Occurrence Handle11738108 Occurrence Handle10.1016/S0168-8278(01)00214-8 Occurrence Handle1:STN:280:DC%2BD3Mnpt1Sluw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  22. J Blackberg K Kidd-Ljunggren (2000) ArticleTitleOccult hepatitis B virus after acute self-limited infection persisting for 30 years without sequence variation J Hepatol 33 992–7 Occurrence Handle11131464 Occurrence Handle10.1016/S0168-8278(00)80134-8 Occurrence Handle1:STN:280:DC%2BD3M7it1Omsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  23. N Yuki T Nagaoka M Yamashiro K Mochizuki A Kaneko K Yamamoto et al. (2003) ArticleTitleLong-term histologic and virologic outcomes of acute self-limited hepatitis B Hepatology 37 1172–9 Occurrence Handle12717399 Occurrence Handle10.1053/jhep.2003.50171 Occurrence Handle1:CAS:528:DC%2BD3sXktVWnsb8%3D

    Article  PubMed  CAS  Google Scholar 

  24. JC Sheu GT Huang LN Shih WC Lee HC Chou JT Wang et al. (1992) ArticleTitleHepatitis C and B viruses in hepatitis B surface antigen-negative hepatocellular carcinoma Gastroenterology 103 1322–7 Occurrence Handle1327934 Occurrence Handle1:STN:280:DyaK3s%2Fht1Oisw%3D%3D

    PubMed  CAS  Google Scholar 

  25. C Brechot D Gozuacik Y Murakami P Paterlini-Brechot (2000) ArticleTitleMolecular bases for the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) Semin Cancer Biol 10 211–31 Occurrence Handle10936070 Occurrence Handle10.1006/scbi.2000.0321 Occurrence Handle1:CAS:528:DC%2BD3cXlsVKks74%3D

    Article  PubMed  CAS  Google Scholar 

  26. MF Yuen Y Tanaka M Mizokami JC Yuen DK Wong HJ Yuan et al. (2004) ArticleTitleRole of hepatitis B virus genotypes Ba and C, core promoter and precore mutations in hepatocellular carcinoma: a case control study Carcinogenesis 25 1593–8 Occurrence Handle15090469 Occurrence Handle10.1093/carcin/bgh172 Occurrence Handle1:CAS:528:DC%2BD2cXntFahsr0%3D

    Article  PubMed  CAS  Google Scholar 

  27. 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 

  28. JH Kao PJ Chen MY Lai DS Chen (2002) ArticleTitleSequence analysis of pre-S/surface and pre-core/core promoter genes of hepatitis B virus in chronic hepatitis C patients with occult HBV infection J Med Virol 68 216–20 Occurrence Handle12210410 Occurrence Handle10.1002/jmv.10188 Occurrence Handle1:CAS:528:DC%2BD38Xntlaqtb4%3D

    Article  PubMed  CAS  Google Scholar 

  29. J Ludwig TR Viggiano DB McGill BJ Oh (1980) ArticleTitleNonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease Mayo Clin Proc 55 434–8 Occurrence Handle7382552 Occurrence Handle1:STN:280:DyaL3c3gvVeqtQ%3D%3D

    PubMed  CAS  Google Scholar 

  30. Y Falck-Ytter ZM Younossi G Marchesini AJ McCullough (2001) ArticleTitleClinical features and natural history of nonalcoholic steatosis syndromes Semin Liver Dis 21 17–26 Occurrence Handle11296693 Occurrence Handle10.1055/s-2001-12926 Occurrence Handle1:STN:280:DC%2BD3MrgsVGrsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  31. G Marchesini M Brizi G Bianchi S Tomassetti E Bugianesi M Lenzi et al. (2001) ArticleTitleNonalocoholic fatty liver disease: a feature of the metabolic syndrome Diabetes 50 1844–50 Occurrence Handle11473047 Occurrence Handle10.2337/diabetes.50.8.1844 Occurrence Handle1:CAS:528:DC%2BD3MXlslKmsr4%3D

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Atsunori Kusakabe, Yasuhito Tanaka, Fuat Kurbanov, Tomoyuki Sakamoto, Noboru Shinkai & Masashi Mizokami

  2. Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Atsunori Kusakabe, Etsuro Orito, Fuminaka Sugauchi, Tomoyuki Sakamoto, Noboru Shinkai & Ryuzo Ueda

  3. Handa Higasi Clinic, Handa, Japan

    Noboru Hirashima

  4. Department of Gastroenterology, Chukyo Hospital, Nagoya, Japan

    Izumi Hasegawa & Tomoyoshi Ohno

Authors
  1. Atsunori Kusakabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuhito Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Etsuro Orito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fuminaka Sugauchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fuat Kurbanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomoyuki Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Noboru Shinkai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Noboru Hirashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Izumi Hasegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tomoyoshi Ohno
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ryuzo Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Masashi Mizokami
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kusakabe, A., Tanaka, Y., Orito, E. et al. A weak association between occult HBV infection and non-B non-C hepatocellular carcinoma in Japan. J Gastroenterol 42, 298–305 (2007). https://doi.org/10.1007/s00535-006-1999-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-006-1999-3

Key words

Search

Navigation