Skip to main content

Advertisement

SpringerLink
Log in

Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease, alcoholic liver disease, and chronic liver disease of unknown etiology: report of the nationwide survey

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

Abstract

Purpose

To clarify the etiology of hepatocellular carcinoma (HCC) in Japanese patients with non-viral liver disease, we performed a nationwide survey. The influence of obesity, lifestyle-related diseases, and alcohol consumption was focused on.

Methods

A nationwide survey of 14,530 HCC patients was conducted in 2009. Clinical features were studied for HCC patients with nonalcoholic fatty liver disease (NAFLD-HCC; n = 292), alcoholic liver disease (ALC-HCC; n = 991), and chronic liver disease of unknown etiology (unknown HCC; n = 614). The unknown HCC was divided into two subgroups, a no alcohol intake group and a modest alcohol intake group.

Results

ALC-HCC accounted for 7.2% of all HCC, followed by unknown HCC (5.1%) and NAFLD-HCC (2.0%). The characteristics of these three groups were clearly different (median age was 72 years for NAFLD-HCC, 68 years for ALC-HCC, and 73 years for unknown HCC, p < 0.01; female gender was 38, 4, and 37%, respectively, p < 0.01). Obesity and lifestyle-related diseases were significantly more frequent in NAFLD-HCC than in ALC-HCC and unknown HCC. The no alcohol intake subgroup of unknown HCC showed female predominance (58%) and was older, without a high prevalence of obesity and lifestyle-related diseases. In contrast, the modest alcohol intake subgroup showed the same trends regarding gender, body mass index, prevalence of lifestyle-related diseases, and liver function as the ALC-HCC group.

Conclusions

The clinical features of ALC-HCC, NAFLD-HCC, and unknown HCC were clearly different. Modest intake of alcohol might have a more significant role in hepatic carcinogenesis than is presently thought.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. World Health Organization. Mortality database. http://www.who.int/whosis/en (Accessed February 2010).

  2. Bosch FX, Ribes J, Díaz M, Cléries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004;127(5 Suppl 1):S5–16.

    Article  PubMed  Google Scholar 

  3. Sherman M. Hepatocellular carcinoma: epidemiology, risk factors and screening. Semin Liver Dis. 2005;25:143–5.

    Article  PubMed  Google Scholar 

  4. Health and Welfare Statistics Association. J Health Welf Stat. 2009;56(9):39–89.

  5. Ikai I, Kudo M, Arii S, Omata M, Kojiro M, Sakamoto M, et al. Report of the 18th follow-up survey of primary liver cancer. Hepatol Res. 2010;40:1043–59.

    Google Scholar 

  6. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology. 2010;51:1820–32.

    Article  PubMed  Google Scholar 

  7. Siegel AB, Zhu AX. Metabolic syndrome and hepatocellular carcinoma: two growing epidemics with a potential link. Cancer. 2009;115:5651–61.

    Article  PubMed  Google Scholar 

  8. Moller H, Mellemgaard A, Lindvig K, Olsen JH. Obesity and cancer risk: a Danish record-linkage study. Eur J Cancer. 1994;30A:344–50.

    Article  PubMed  CAS  Google Scholar 

  9. Ratziu V, Bellentani S, Cortez-Pinto H, Day C, Marchesini G. A position statement on NAFLD/NASH based on the EASL 2009 special conference. J Hepatol. 2010;53:372–84.

    Article  PubMed  Google Scholar 

  10. Takada A, Tsutsumi M. National survey of alcoholic liver disease in Japan (1968–91). J Gastroenterol Hepatol. 1995;10:509–16.

    Article  PubMed  CAS  Google Scholar 

  11. Purohit V, Khalsa J, Serrno J. Mechanisms of alcohol-associated cancers: introduction and summary of the symposium. Alcohol. 2005;35:155–60.

    Article  PubMed  Google Scholar 

  12. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD single topic conference. Hepatology. 2003;37:1202–19.

    Article  PubMed  Google Scholar 

  13. Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis. 2004;2:3–20.

    Google Scholar 

  14. Matsuzawa Y, Inoue S, Ikeda Y, Sakata T, Saitou Y, Satou Y et al. New diagnosis and classification of obesity. J Jpn Soc Study Obes. 2000:6:18–28 (in Japanese).

    Google Scholar 

  15. Examination Committee of Criteria for Metabolic Syndrome in Japan. Definition and diagnosis for metabolic syndrome. J Jpn Soc Intern Med. 2005;94:784–809 (in Japanese).

    Google Scholar 

  16. Michitaka K, Nishiguchi S, Aoyagi Y, Hiasa Y, Tokumoto Y, Onji M, Japan Etiology of Liver Cirrhosis Study Group. Etiology of liver cirrhosis in Japan: a nationwide survey. J Gastroenterol. 2010;45:86–94.

    Article  PubMed  Google Scholar 

  17. Malik SM, Gupte PA, de Vera ME, Ahmad J. Liver transplantation in patients with nonalcoholic steatohepatitis-related hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2009;7:800–6.

    Article  PubMed  Google Scholar 

  18. Marrero JA, Fontana RJ, Su GL, Conjeevaram HS, Emick DM, Lok AS. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology. 2002;36:1349–54.

    PubMed  Google Scholar 

  19. Bralet MP, Régimbeau JM, Pineau P, Dubois S, Loas G, Degos F, et al. Hepatocellular carcinoma occurring in nonfibrotic liver: epidemiologic and histopathologic analysis of 80 French cases. Hepatology. 2000;32:200–4.

    Article  PubMed  CAS  Google Scholar 

  20. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(5 Suppl 1):S35–50.

    Google Scholar 

  21. Davis GL, Dempster J, Meler JD, Orr DW, Walberg MW, Brown B, et al. Hepatocellular carcinoma: management of an increasingly common problem. Proc (Bayl Univ Med Cent). 2008;21:266–80.

    Google Scholar 

  22. Arao M, Murase K, Kusakabe A, Yoshioka K, Fukuzawa Y, Ishikawa T, et al. Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus. J Gastroenterol. 2003;38:355–60.

    Article  PubMed  Google Scholar 

  23. El-serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology. 2004;126:460–8.

    Article  PubMed  Google Scholar 

  24. Browning JD, Kumar KS, Saboorian MH, Thiele DL. Ethnic differences in the prevalence of cryptogenic cirrhosis. Am J Gastroenterol. 2004;99:292–8.

    Article  PubMed  Google Scholar 

  25. Ong J, Younossi ZM, Reddy V, Price LL, Gramlich T, Mayes J, et al. Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease. Liver Transpl. 2001;7:797–801.

    Article  PubMed  CAS  Google Scholar 

  26. Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 2007;317(5834):121–4.

    Article  PubMed  CAS  Google Scholar 

  27. Nakagawa H, Maeda S, Yoshida H, Tateishi R, Masuzaki R, Ohki T et al. Serum IL-6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C patients: an analysis based on gender differences. Int J Cancer. 2009;125:2264–9.

    Google Scholar 

  28. Yoshioka Y, Hashimoto E, Yatsuji S, Kaneda H, Taniai M, Tokushige K, et al. Nonalcoholic steatohepatitis: cirrhosis, hepatocellular carcinoma, and burnt-out NASH. J Gastroenterol. 2004;39:1215–8.

    Article  PubMed  Google Scholar 

  29. Higashi Y, Tada S, Miyase S, Hirota K, Imamura H, Kamio T, et al. Correlation of clinical characteristics with detection of hepatitis B virus X gene in liver tissue in HBsAg-negative, and HCV-negative hepatocellular carcinoma patients. Liver. 2002;22:374–9.

    Article  PubMed  Google Scholar 

  30. Ayata G, Gordon FD, Lewis WD, Pomfret E, Pomposelli JJ, Jenkins RL, et al. Cryptogenic cirrhosis: clinicopathologic findings at and after liver transplantation. Hum Pathol. 2002;33(11):1098–104.

    Article  PubMed  Google Scholar 

  31. Tokushige K, Hashimoto E, Yatsuji S, Tobari M, Taniai M, Torii N, et al. Prospective study of hepatocellular carcinoma in nonalcoholic steatohepatitis in comparison with hepatocellular carcinoma caused by chronic hepatitis C. J Gastroenterol. 2010;45:960–7.

    Article  PubMed  CAS  Google Scholar 

  32. Tokushige K, Hashimoto E, Tobari M, Yatsuji S, Takakura M, Taniai M et al. The effect of previous HBV infection on hepatocellular carcinoma with alcoholic liver disease. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2006;41:120–7 (in Japanese).

    Google Scholar 

  33. Ascha MS, Hanouneh IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology. 2010;51:1972–8.

    Article  PubMed  Google Scholar 

  34. Suzuki A, Angulo P, St Sauver J, Muto A, Okada T, Lindor K. Light to moderate alcohol consumption is associated with lower frequency of hypertransaminasemia. Am J Gastroenterol. 2007;102:1912–9.

    Article  PubMed  Google Scholar 

  35. Mandayam S, Jamal MM, Morgan TR. Epidemiology of alcoholic liver disease. Semin Liver Dis. 2004;24:217–32.

    Article  PubMed  Google Scholar 

  36. Bellentani S, Saccoccio G, Costa G, Tiribelli C, Manenti F, Sodde M, et al. Drinking habits as cofactors of risk for alcohol induced liver damage. The Dionysos Study Group. Gut. 1997;41:845–50.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by a grant-in aid from the Ministry of Health, Labour and Welfare of Japan.

Author information

Authors and Affiliations

  1. Department of Internal Medicine and Gastroenterology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Katsutoshi Tokushige, Etsuko Hashimoto & Makiko Taniai

  2. Department of Internal Medicine, International University of Health and Welfare, Sanno Hospital, Tokyo, Japan

    Yoshinori Horie

  3. National Hospital Organization Kurihama Alcoholism Center, Yokosuka, Kanagawa, Japan

    Susumu Higuchi

Authors
  1. Katsutoshi Tokushige
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Etsuko Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshinori Horie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Makiko Taniai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Susumu Higuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Etsuko Hashimoto.

Additional information

We wish to dedicate this paper to the memory of Dr. Hiromasa Ishii, who passed away on May 31, 2010, while we were writing this manuscript after finishing research that was supported by grants from the Japanese Ministry of Health, Labour and Welfare between 2007 and 2009. He was the chief researcher for grants and we know how much he meant to our group as a fine leader.

Appendix

Appendix

Aichi Medical University Hospital, Aichi Saiseikai Hospital, Aikawa naika Hospital, Aiseikai Yamashina Hospital, Akita University Hospital, Arita GI Hospital, Chiba University Hospital, Department of Digestive and Life-style Related Disease Health Research Course Human and Environmental Sciences Kagoshima University Graduate school of Medical and Dental Sciences, Department of Medicine Hematology Gastroenterology Endocrinology Metabology Nippon Medical School Hospital, Division of Gastroenterology and Hematology Department of Internal Medicine Faculty of Medicine University of Miyazaki, Dohkohkai Hospital, Ehime University Graduate school of Medicine,Department of Gastroenterology and Metabology, EIJU General Hospital, First Department of internal Medicine Faculty of Medicine University of Yamanashi, Fujisawa Shounandai Hospital, Fukuoka University Hospital, Fukushima Medical University Hospital, Graduate school of Medicine Faculty of Medicine Osaka University, Gunma University Hospital, Hachioji Syokaki Hospital, Hakodate City Hospital, Hamamatsu University School of Medicine University Hospital, Harada Hospital, Heart Life Hospital, Hirosaki University School of Medicine & Hospital, Hiroshima University Hospital, Hokkaido P.W.F.A.C Engaru-Kosei General Hospital, Iseikai Hospital, IUHW Atami Hospital, Japan Labour Health and Welfare Kanto Rosai Hospital, Japan Labour Health and Welfare Osaka Rosai Hospital, Japan Post Kyoto Teishin Hospital, Japan Self Defense Forces Hanshin Hospital, Japanese Red Cross Fukuoka Hospital, Japanese Red Cross Koga Hospital, JR Tokyo General Hospital, Juntendo University Hospital, Kagoshima City Hospital, Kameda Medical Center, Kamigoto Hospital, Kansai Medical University Takii Hospital, Kashiwa City Hospital, Kawasaki City Tama Hospital, Kawasaki Medical School Hospital, Kikugawa General Hospital, Kimotsuki-gun Medical Associated Hospital, Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Kinki University Hospital, Kirishima Medical Center, Kobe Asahi Hospital, Kochi Health Sciences Center, Kohnodai Hospital National Center for Global Health and Medicine, Kubo Hospital, Kumamoto University Hospital, Kurashiki Central Hospital, Kurume University Hospital, Kyorin University Hospital, Kyoto Prefectural Yosanoumi Hospital, Matsue Coop General Hospital, Matsushita Memorial Hospital, Meiwa Hospital, Mie University Hospital, Mitsubishi Kyoto Hospital, Mitsubishi Nagasaki Hospital, Nagasaki Municipal Medical Center, Nagasaki University Hospital, National Cancer Center Hospital, National Hospital Organization Kyoto Medical Center, National Hospital Organization Osaka Minami Medical Center, National Hospital Organization Sagamihara National Hospital, National Hospital Organization Tokyo National Hospital, Nihon University Itabashi Hospital, Niigata Prefecture Yoshida Hospital, Niigata University Medical & Dental Hospital, Niitsu Medical Center Hospital, Nippon Medical University Musasi Kosugi Hospital, Oita University Hospital, Oji General Hospital, Okayama Saiseikai General Hospital, Ono Municipal Hospital, Osaka City University Hospital, Osaka Police Hospital, Prefecture Nagano Kiso Hospital, Saga University Hospital, Saiseikai Kawaguchi General Hospital, Saiseikai Yokohamashi Nanbu Hospital, Saitama City Hospital, Saitama Cooperative Hospital, Saitama Medical University Hospital, Saitama Shakai Hoken Hospital, Shimane University Hospital Faculty of Medicine, Shinkoga Hospital, Showa General Hospital, Showa University Fujigaoka Hospital, Showa University Hospital, St. Marianna University School of Medicine Western part of Yokohama City Hospital, Tama-nanbu chiiki Hospital, Teikyo University Mizonokuchi Hospital, The Hospital of Hyogo College of Medicine, The Sakakibara Heart Institute of Okayama, Toho University Omori Medical Center, Tokoname Municipal Hospital, Tokushima University Hospital, Tokyo Kosei Nenkin Hospital, Tokyo Medical and Dental University Hospital Faculty of Medicine, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo Women’s Medical University Hospital, Tokyo Women’s Medical University Medical Center East, Toshiba Hospital, Tottori University Hospital, Yamagata University Hospital Department of Gastroenterology, Yodakubo Hospital, Yokohama City University Hospital, Yokohama General Hospital, Yokosuka Kyosai Hospital, Yokosuka Kyosai Hospital, Yokote Municipal Hospital.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tokushige, K., Hashimoto, E., Horie, Y. et al. Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease, alcoholic liver disease, and chronic liver disease of unknown etiology: report of the nationwide survey. J Gastroenterol 46, 1230–1237 (2011). https://doi.org/10.1007/s00535-011-0431-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-011-0431-9

Keywords

Search

Navigation