Skip to main content

Advertisement

SpringerLink
Log in

Etiology of non-B non-C hepatocellular carcinoma in the eastern district of Tokyo

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

Abstract

Background

This study was carried out to clarify the carcinogenic factors associated with nonviral hepatocellular carcinoma (HCC).

Methods

A total of 320 HCC patients diagnosed and treated from January 2000 to December 2006 were enrolled. The clinical characteristics of non-B non-C HCC patients were examined to determine possible carcinogenic factors.

Results

Of 320 HCC patients, 64 were classified as having non-B non-C HCC. The proportion of non-B non-C HCC increased from 17.8% in 2000 to 28.6% in 2006. Non-B non-C HCC patients had a significantly higher rate of early stage cirrhosis (Child-Pugh classification) than viral HCC patients. Significantly fewer non-B non-C HCC patients had periodic intensive medical assessments than viral HCC patients. Forty-five non-B non-C HCC patients were habitual alcohol drinkers, ten had nonalcoholic fatty liver disease (NAFLD), and seven had no apparent etiology. In habitual drinkers, the stage of underlying liver disease varied widely, while most NAFLD patients had early stage cirrhosis. On the other hand, more than half of the patients with HCC of undetermined etiology had noncirrhotic liver disease. Among habitual drinkers, the underlying liver disease was more progressive, and the T stage was more advanced in those with high daily alcohol intake than in those with low daily alcohol intake. Periodic intensive medical assessments were crucial for detecting early stage HCC.

Conclusions

Alcohol consumption and NAFLD may be important etiological factors in non-B non-C HCC. Periodic medical assessments for all patients with non-B non-C cirrhosis are crucial for early diagnosis and curative therapy.

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. Ikeda K, Saitoh S, Koida I, Arase Y, Tsubota A, Chayama K, et al. A multivariate analysis of risk factors for hepatocellular carcinoma: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology 1993;18:47–53.

    Article  PubMed  CAS  Google Scholar 

  2. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma: conclusions of the Barcelona-2000 EASL conference. J Hepatol 2001;35:421–430.

    Article  PubMed  CAS  Google Scholar 

  3. Ikai I, Okita K, Omata M, Kojiro M, Kobayashi K, Nakamura Y, et al. Report of the 15th follow-up survey of primary liver cancer. Hepatol Res 2004;28:21–29.

    Article  PubMed  Google Scholar 

  4. Noguchi K, Nakashima O, Nakashima Y, Shirota K, Nawata H, Kojiro M. Clinicopathological study on hepatocellular carcinoma negative for hepatitis B surface antigen and antibody to hepatitis C virus. Int J Mol Med 2000;6:661–665.

    PubMed  CAS  Google Scholar 

  5. Koike Y, Shiratori Y, Sato S, Obi S, Teratani T, Imamura M, et al. Risk factors for recurring hepatocellular carcinoma differ according to infected hepatitis virus—an analysis of 236 consecutive patients with a single lesion. Hepatology 2000;32:1216–1223.

    Article  PubMed  CAS  Google Scholar 

  6. Yotsuyanagi H, Shintani Y, Moriya K, Fujie H, Tsutsumi T, Kato T, et al. Virologic analysis of non-B non-C hepatocellular carcinoma in Japan: frequent involvement of hepatitis B virus. J Infect Dis 2000;181:1920–1928.

    Article  PubMed  CAS  Google Scholar 

  7. Takaguchi K, Satou A, Ando M, Nishihara T, Kita K, Ogawa H, et al. Detection of hepatitis B virus DNA in the liver and serum of patients with hepatitis B surface antigen and hepatitis C virus antibody negative chronic liver disease. Hepatol Res 2002;22:139–144.

    Article  PubMed  CAS  Google Scholar 

  8. Kazemi-Shirazi L, Petermann D, Muller C. Hepatitis B virus DNA in sera and liver tissue of HBsAg negative patients with chronic hepatitis C. J Hepatol 2000;33:785–790.

    Article  PubMed  CAS  Google Scholar 

  9. Britto MR, Thomas LA, Balaratnam N, Griffiths AP, Duane PD. Hepatocellular carcinoma arising in non-cirrhotic liver in genetic haemochromatosis. Scand J Gastroenterol 2000;35:889–893.

    Article  PubMed  CAS  Google Scholar 

  10. Matsui S, Ichida T, Watanabe M, Sugitani S, Suda T, Takahashi T, et al. Clinical features and etiology of hepatocellular carcinoma arising in patients with membranous obstruction of the inferior vena cava: in reference to hepatitis viral infection. J Gastroenterol Hepatol 2000;15:1205–1211.

    Article  PubMed  CAS  Google Scholar 

  11. Horie Y, Yamagishi Y, Kajihara M, Kato S, Ishii H. National survey of hepatocellular carcinoma in heavy drinkers in Japan. Alcohol Clin Exp Res 2003;27:32S–36S.

    Article  PubMed  Google Scholar 

  12. Angulo P, Keach J, Batts K, Lindor K. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999;30:1356–1362.

    Article  PubMed  CAS  Google Scholar 

  13. Aizawa Y, Shibamoto Y, Takagi I, Zeniya M, Toda G. Analysis of factors affecting the appearance of hepatocellular carcinoma in patients with chronic hepatitis C. A long term follow-up study after histologic diagnosis. Cancer 2000;1;89:53–59.

    Article  Google Scholar 

  14. Cotrim H, Parana R, Braga E, Lyra L. Nonalcoholic steatohepatitis and hepatocellular carcinoma: natural history? Am J Gastroenterol 2000;95:3018–3019.

    Article  PubMed  CAS  Google Scholar 

  15. Zen Y, Katayanagi K, Tsuneyama K, Harada K, Araki I, Nakamura Y. Hepatocellular carcinoma arising in non-alcoholic steatohepatitis. Pathol Int 2001;51:127–131.

    Article  PubMed  CAS  Google Scholar 

  16. Shimada M, Hashimoto E, Taniai M, Hasegawa K, Okuda H, Hayashi N, et al. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. J Hepatol 2002;37:154–160.

    Article  PubMed  Google Scholar 

  17. Adami HO, McLaughlin J, Ekbom A, Berne C, Silverman D, Hacker D, et al. Cancer risk in patients with diabetes mellitus. Cancer Causes Control 1991;2:307–314.

    Article  PubMed  CAS  Google Scholar 

  18. La Vecchia C, Negri E, Franschi SD, D’Avanzo B, Boyle P. A case-control study of diabetes mellitus and cancer risk. Br J Cancer 1994;70:950–953.

    PubMed  Google Scholar 

  19. Lagiou P, Kuper H, Stuver S, Tzonou A, Trichopoulos D, Adami HO. Role of diabetes mellitus in the etiology of hepatocellular carcinoma. J Natl Cancer Inst 2000;92:1096–1099.

    Article  PubMed  CAS  Google Scholar 

  20. Fujino Y, Mizoue T, Tokui N, Yoshimura T. Prospective study of diabetes mellitus and liver cancer in Japan. Diabetes Metab Res Rev 2001;17:374–379.

    Article  PubMed  CAS  Google Scholar 

  21. El-Serag HB, Richardson PA, Everhart JE. The role of diabetes in hepatocellular carcinoma: a case-control study among United States veterans. Am J Gastroenterol 2001;96:2462–2467.

    Article  PubMed  CAS  Google Scholar 

  22. Tazawa J, Maeda M, Nakagawa M, Ohbayashi H, Kusano F, Yamane M, et al. Diabetes mellitus may be associated with hepatocarcinogenesis in patients with chronic hepatitis C. Dig Dis Sci 2002;47:710–715.

    Article  PubMed  Google Scholar 

  23. Hassan M, Hwang L, Hatten C, Swain M, Li D, Abbruzzese J, et al. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology 2002;36:1206–1213.

    Article  PubMed  CAS  Google Scholar 

  24. Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, et al., eds. AJCC cancer staging manual. 5th ed. Philadelphia: Lippincott-Raven; 1997.

    Google Scholar 

  25. Ikeda K, Saitoh S, Kobayashi M, Suzuki Y, Tsubota A, Suzuki F, et al. Distinction between chronic hepatitis and liver cirrhosis in patients with hepatitis C virus infection. Practical discriminant function using common laboratory data. Hepatol Res 2000;18:252–256.

    Article  PubMed  Google Scholar 

  26. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60:646–649.

    Article  PubMed  CAS  Google Scholar 

  27. Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology 1999;29:664–669.

    Article  PubMed  CAS  Google Scholar 

  28. Nishiguchi S, Kuroki T, Nakatani S, Morimoto H, Takeda T, Nakajima S, et al. Randomized trial of effects of interferon-α on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. Lancet 1995;346:1051–1055.

    Article  PubMed  CAS  Google Scholar 

  29. Yoshizawa H, Tanaka J, Miyakawa Y. National prevention of hepatocellular carcinoma in Japan based on epidemiology of hepatitis C virus infection in the general population. Intervirology 2006;49:7–17.

    Article  PubMed  Google Scholar 

  30. Ohhira M, Fujimoto Y, Matsumoto A, Ohtake T, Ono M, Kohgo Y. Hepatocellular carcinoma associated with alcoholic liver disease: a clinicopathological study and genetic polymorphism of aldehyde dehydrogenase 2. Alcohol Clin Exp Res 1996;20:378A–382A.

    PubMed  CAS  Google Scholar 

  31. Purohit V, Khalsa J, Serrano J. Mechanisms of alcohol-associated cancers: introduction and summary of the symposium. Alcohol 2005;35:155–160.

    Article  PubMed  Google Scholar 

  32. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006;295:65–73.

    Article  PubMed  CAS  Google Scholar 

  33. Shimada S, Aizawa R, Abe H, Suto S, Miyakawa Y, Aizawa Y. Analysis of risk factors for hepatocellular carcinoma that is negative for hepatitis B surface antigen (HBsAg). Intern Med 2003;42:389–393.

    Article  PubMed  Google Scholar 

  34. Poonawala A, Nair SP, Thuluvath PJ. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a case-control study. Hepatology 2000;32:689–692.

    Article  PubMed  CAS  Google Scholar 

  35. Diehl AM. Nonalcoholic steatohepatitis. Semin Liver Dis 1999;16:221–229.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Aoto Hospital, 6-41-2 Aoto, Katsushika-ku, Tokyo, 125-8506, Japan

    Hiroshi Abe, Kai Yoshizawa, Takuya Kitahara, Ryoichi Aizawa, Mika Matsuoka & Yoshio Aizawa

Authors
  1. Hiroshi Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kai Yoshizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takuya Kitahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ryoichi Aizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mika Matsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshio Aizawa
    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

Abe, H., Yoshizawa, K., Kitahara, T. et al. Etiology of non-B non-C hepatocellular carcinoma in the eastern district of Tokyo. J Gastroenterol 43, 967–974 (2008). https://doi.org/10.1007/s00535-008-2264-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-008-2264-8

Key words

Search

Navigation