Skip to main content

Advertisement

SpringerLink
Log in

The epidemiology of hepatocellular cancer: from the perspectives of public health problem to tumor biology

  • International Forum 2
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

The epidemiology of hepatocellular cancer (HCC) can be viewed from several important perspectives. The conventional perspective includes the overall public health impact of HCC, which is increasing in incidence in many regions of the world. The epidemiology of HCC can also be viewed from the perspective of variation in underlying disease associations such as viral hepatitis or the recently recognized link to nonalcoholic fatty liver disease (NAFLD). Of perhaps increasing importance with recent advances in therapy of HCC, the epidemiology of HCC can also be viewed from the perspective of variation in HCC biology. This lesser known perspective may depend in part on the underlying liver disease and the cell origin of the cancer, whether of hepatocyte or stem cell origin. This aspect is likely to become central to diagnosis and management of HCC with the further development of targeted therapeutics. The relative efficacy of these agents will likely depend on the biochemical pathways active in a given hepatocellular malignancy. This, in turn, is likely to be related to the epidemiological associations of HCC.

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.

Similar content being viewed by others

References

  1. Pisani P, Bray F, Parkin DM. Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. Int J Cancer 2002;97(1):72–81.

    Article  PubMed  CAS  Google Scholar 

  2. Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer 2001;94(2):153–156.

    Article  PubMed  CAS  Google Scholar 

  3. Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology 2004;127:S5–S16.

    Article  PubMed  Google Scholar 

  4. Bosch FX, Ribes J, Cleries R, Diaz M. Epidemiology of hepatocellular carcinoma. Clinics in Liver Disease 2005;9:191–211.

    Article  PubMed  Google Scholar 

  5. Yu MW, Chang HC, Chang SC, Liaw YF, Lin SM, Liu CJ, et al. Role of reproductive factors in hepatocellular carcinoma: Impact on hepatitis B- and C-related risk. Hepatology 2003;38:1393–1400.

    PubMed  Google Scholar 

  6. De Maria N, Manno M, Villa E. Sex hormones and liver cancer. Mol Cell Endocrinol 2002;193:59–63.

    Article  PubMed  Google Scholar 

  7. Rogers AB, Theve EJ, Feng Y, Fry RC, Taghizadeh K, Clapp KM, et al. Hepatocellular carcinoma associated with liver-gender disruption in male mice. Cancer Res 2007;67:11536–11546.

    Article  PubMed  CAS  Google Scholar 

  8. Kiyosawa K, Umemura T, Ichijo T, Matsumoto A, Yoshizawa K, Gad A, et al. Hepatocellular carcinoma: recent trends in Japan. Gastroenterology 2004;127(5 suppl 1):S17–S26.

    Article  PubMed  Google Scholar 

  9. Jepsen P, Vilstrup H, Tarone RE, Friis S, Sorensen HT. Incidence rates of hepatocellular carcinoma in the U.S. and Denmark: recent trends. Int J Cancer 2007;121(7):1624–1626.

    Article  PubMed  CAS  Google Scholar 

  10. El-Serag HB, Mason HC. Rising incidence of hepatocellular carcinoma in the Unites States. N Engl J Med 1999;19:221–229.

    Google Scholar 

  11. Kim WR, Gores GJ, Benson JT, Therneau TM, Melton LJ. Mortality and hospital utilization for hepatocellular cancer in the United States. Gastroenterology 2005;129:486–493.

    PubMed  Google Scholar 

  12. El-Serag HB, Lau M, Eschbach K, Davila J, Goodwin J. Epidemiology of hepatocellular carcinoma in Hispanics in the United States. Archives of Internal Medicine 2007;167:1983–1989.

    Article  PubMed  Google Scholar 

  13. Di Bisceglie AM, Lyra AC, Schwartz M, Reddy RK, Martin P, Gores G, et al. Liver Cancer Network. Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status. Am J Gastroenterol 2003;98(9):2060–2063.

    Article  PubMed  Google Scholar 

  14. Yu MC, Yuan JM. Environmental factors and risk for hepatocellular carcinoma. Gastroenterology 2004;127(5 suppl 1):S72–S78.

    Article  PubMed  CAS  Google Scholar 

  15. Zhang Y-J, Chen Y, Ahsan H, Lunn RM, Chen S-Y, Lee PH, et al. Silencing glutathione S-transferase P1 by promoter hypermethylation and its relationship to environmental chemical carcinogens in hepatocellular cancer. Cancer Lett 2005;221:135–143.

    Article  PubMed  CAS  Google Scholar 

  16. Hoque A, Patt YZ, Yoffe B, Groopman JD, Greenblatt MS, Zhang YJ, et al. Does aflatoxin B1 play a role in the etiology of hepatocellular carcinoma in the United States? Nutr Cancer 1999;35:27–33.

    Article  PubMed  CAS  Google Scholar 

  17. La Vecchia C. Alcohol and liver cancer. Eur J Cancer Prev 2007;16:495–497.

    PubMed  Google Scholar 

  18. Hara M, Tanaka K, Higaki Y, Mizuta T, Eguchi Y, Yasutake T, et al. Case-control study on cigarette smoking and the risk of hepatocellular carcinoma among Japanese. Cancer Sci 2008;99:93–97.

    PubMed  CAS  Google Scholar 

  19. Chiu HF, Ho SC, Wang LY, Wu TN, Yang CY. Does arsenic exposure increase the risk for liver cancer? J Toxicol Environ Health Part A 2004;67:1491–1500.

    Article  PubMed  CAS  Google Scholar 

  20. Cotrim HP, Carvalho F, Siquiera AC, Lordelo M, Rocha R, De Freitas LA. Nonalcoholic fatty liver and insulin resistance among petrochemical workers. JAMA 2005;294:1618–1620.

    Article  PubMed  CAS  Google Scholar 

  21. Kumar M, Kumar R, Hissar SS, Saraswat MK, Sharma BC, Sakhuja P, et al. Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: a case-control study of 213 hepatocellular carcinoma patients from India. J Gastroenterol Hepatol 2007;22:1104–1111.

    Article  PubMed  Google Scholar 

  22. Yu M-W, Yeh S-H, Chen P-J, Liaw Y-F, Lin C-L, Liu CJ, et al. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: a prospective study in men. J Natl Cancer Inst 2005;97:265–272.

    Article  PubMed  CAS  Google Scholar 

  23. Changchien C-S, Chen C-L, Yen Y-H, Wang J-H, Hu T-H, Lee C-M, et al. Analysis of 6381 hepatocellular carcinoma patients in southern Taiwan: prognostic features, treatment outcomes and survival. J Gastroenterol 2008;43:159–170.

    Article  PubMed  CAS  Google Scholar 

  24. Brechot C, Jaffredo F, Lagorce D, Gerken G, Meyer zum Buschenfelde K, Papakonstontinou A, et al. Impact of HBV, HCV, and GBV-C/HGV on hepatocellular carcinoma in Europe: results of a European concerted action. J Hepatol 1998;29:173–183.

    Article  PubMed  CAS  Google Scholar 

  25. Park J-W. Hepatocellular carcinoma in Korea: introduction and overview. Korean J Gastroenterol 2005;45:217–226.

    PubMed  Google Scholar 

  26. Fattovich G, Giustina G, Degos F, Tremolada F, Diodati G, Almasio P, et al. Morbidity and mortality in compensated cirrhosis type C: a retrospective follow-up study of 384 patients. Gastroenterology 1997;112(2):463–472.

    Article  PubMed  CAS  Google Scholar 

  27. Seeff LB. The burden of hepatocellular carcinoma. Gastroenterology 2004;127:S1–S4.

    Article  PubMed  Google Scholar 

  28. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907–1917.

    Article  PubMed  Google Scholar 

  29. Bruix J, Sherman M. Management of hepatocellular carcinoma: AASLD Practice Guideline. Hepatology 2005;42:1208–1236.

    Article  PubMed  Google Scholar 

  30. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004;127:S35–S50.

    Article  PubMed  Google Scholar 

  31. Terasaki S, Kaneko S, Kobayashi K, Nonomura A, Nakanuma Y. Histological features predicting malignant transformation of nonmalignant hepatocellular nodules: a prospective study. Gastroenterology 1998;115:1216–1222.

    Article  PubMed  CAS  Google Scholar 

  32. Watanabe S, Horie Y, Kataoka E, Sato W, Dohmen T, Ohshima S, et al. Non-alcoholic steatohepatitis and hepatocellular carcinoma: lessons from hepatocyte-specific phosphatase and tensin homolog (Pten)-deficient mice. J Gastroenterol Hepatol 2007;22(suppl 1):S96–S100.

    Article  PubMed  CAS  Google Scholar 

  33. Lew EA, Garfinkle L. Variation in mortality by weight among 750 000 men and women. J Chronic Dis 1979;32:563–76.

    Article  PubMed  CAS  Google Scholar 

  34. Wolk A, Gridley G, Svensson M, Nyren O, McLaughlin JK, Fraumeni JF, et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control 2001;12:13–21.

    Article  PubMed  CAS  Google Scholar 

  35. Moller H, Mellemgaard A, Lindvig K, Olsen J. Obesity and cancer risk: a Danish record-linkage study. Eur J Cancer 1994;30A:344–350.

    Article  PubMed  CAS  Google Scholar 

  36. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 2003;348:1625–1638.

    Article  PubMed  Google Scholar 

  37. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003;37:1202–1219.

    Article  PubMed  Google Scholar 

  38. 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 

  39. Lagiou P, Kuper H, Stuver SO, Tzonou A, Trichopoulos D, Adami H-O. Role of diabetes mellitus in the etiology of hepatocellular carcinoma. J Nat Cancer Inst 2000;92:1096–1099.

    Article  PubMed  CAS  Google Scholar 

  40. Yu L, Sloan DA, Guo C, Howell CD. Risk factors for primary hepatocellular carcinoma in black and white Americans in 2000. Clin Gastroenterol Hepatol 2006;4:355–360.

    Article  PubMed  Google Scholar 

  41. Caldwell SH, Crespo DM, Kang HS, Al-Osaimi AM. Obesity and hepatocellular carcinoma. Gastroenterology 2004;127(suppl 1):S97–S103.

    Article  PubMed  CAS  Google Scholar 

  42. Caldwell SH, Crespo DM. Milestones in liver diseases. The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. J Hepatol 2005;40:578–584.

    Article  Google Scholar 

  43. Bugianesi E. Non-alcoholic steatohepatitis and cancer. Clin Liver Dis 2007;11:191–207.

    Article  PubMed  CAS  Google Scholar 

  44. Ishii H. Hepatocellular carcinoma and non-alcoholic fatty liver disease: major liver diseases emerging from the Asia-Pacific Region. J Gastroenterol Hepatol 2006;21:6–7.

    Article  PubMed  Google Scholar 

  45. Park SH. Nonalcoholic steatohepatitis: pathogenesis and treatment. Korean J Hepatol 2008;14:12–27.

    Article  PubMed  Google Scholar 

  46. Bugianesi E. Non-alcoholic steatohepatitis and cancer. Clin Liver Dis 2007;11:191–207.

    Article  PubMed  CAS  Google Scholar 

  47. Lee V, Kleiner DE, Al-Osaimi AMS, Argo CK, Northup PG, Berg CL, et al. Histological characteristics of patients with “cryptogenic” cirrhosis and prior biopsy showing NASH. Hepatology 2007;46(suppl):743A.

    Google Scholar 

  48. 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;36:1349–1354.

    PubMed  Google Scholar 

  49. Oh KC, Park SH, Park JC, Jin DK, Park CS, Kim KO, et al. Is the incidence of cryptogenic hepatocellular carcinoma increasing in Korea? Korean J Gastroenterol 2005;45:45–51.

    PubMed  Google Scholar 

  50. Powell EE, Jonsson JR, Clouston AD. Steatosis: co-factor in other diseases. Hepatology 2005;42(1):5–12.

    Article  PubMed  CAS  Google Scholar 

  51. Ohata K, Hamasaki K, Toriyama K, Matsumoto K, Saeki A, Yanagi K, et al. Hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C virus infection. Cancer (Phila) 2003;97:3036–3043.

    Article  Google Scholar 

  52. Pekow JR, Bhan AK, Zheng H, Chung RT. Hepatic steatosis is associated with increased frequency of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis. Cancer (Phila) 2007;109:2490–2496.

    Article  Google Scholar 

  53. Ohki T, Tateishi R, Sato T, Masuzaki R, Imamura J, Goto T, et al. Obesity is an independent risk factor for hepatocellular carcinoma development in chronic hepatitis C patients. Clin Gastroenterol Hepatol 2008;6:459.

    Article  PubMed  Google Scholar 

  54. Takuma Y, Nouso K, Makino Y, Saito S, Takayama H, Takahara M, et al. Hepatic steatosis correlates with the postoperative recurrence of hepatitis C virus-associated hepatocellular carcinoma. Liver Int 2007;27(5):620–626.

    Article  PubMed  Google Scholar 

  55. Pitot HC. Pathways of progression in hepatocarcinogenesis. Lancet 2001;358:859–860.

    Article  PubMed  CAS  Google Scholar 

  56. Roskams T, Yang SQ, Koteish A, Durnez A, DeVos R, Huang X, et al. Oxidative stress and oval cell accumulation in mice and humans with alcoholic and nonalcoholic fatty liver disease. Am J Pathol 2003;163:1301–1311.

    PubMed  CAS  Google Scholar 

  57. Hu W, Feng Z, Eveleigh J, Iyer G, Pan J, Amin S, et al. The major lipid peroxidation product, trans-4-hydroxy-2-nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma. Carcinogenesis (Oxf) 2002;23:1781–1789.

    Article  CAS  Google Scholar 

  58. Rossmanith W, Schulte-Hermann R. Biology of transforming growth factor beta in hepatocarcinogenesis. Microsc Res Tech 2001;52:430–436.

    Article  PubMed  CAS  Google Scholar 

  59. Sanchez A, Factor VM, Schroeder IS, Nagy P, Thorgeirsson SS. Activation of NF-κB and STAT3 in rat oval cells during 2-acetylaminoflourene/partial hepatectomy-induced liver regeneration. Hepatology 2004;39:376–385.

    Article  PubMed  CAS  Google Scholar 

  60. Sasaki Y. Does oxidative stress participate in the development of hepatocellular cancer? J Gastroenterol 2006;41:1135–1148.

    Article  PubMed  CAS  Google Scholar 

  61. Durnez A, Verslype C, Nevens F, Fevery J, Aerts R, Pirenne J, et al. The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin. Histopathology (Oxf) 2006;49:138–151.

    Article  CAS  Google Scholar 

  62. Richardson MM, Jonsson JR, Powell EE, Brunt EM, Neuschwander-Tetri BA, Bhathal PS, et al. Progressive fibrosis in non-alcoholic steatohepatitis: association with altered regeneration and a ductular reaction. Gastroenterology 2007;133:80–90.

    Article  PubMed  Google Scholar 

  63. Clouston AD, Powell EE, Walsh MJ, Richardson MM, Demetris AJ, Jonsson JR. Fibrosis correlates with a ductular reaction in hepatitis C: roles of impaired replication, progenitor cells and steatosis. Hepatology 2005:41:809–818.

    Article  PubMed  CAS  Google Scholar 

  64. Schlaeger C, Longerich T, Schiller C, Bewerunge P, Mehrabi A, Toedt G, et al. Etiology-dependent molecular mechanisms in human hepatocarcinogenesis. Hepatology 2008;47:511–520.

    Article  PubMed  CAS  Google Scholar 

  65. Hytiroglou P, Park YN, Krinsky G, Theise ND. Hepatic precancerous lesions and small hepatocellular carcinoma. Gastroenterol Clin N Am 2007;36:867–887.

    Article  Google Scholar 

  66. Roskams T. Liver stem cells and their implications in hepatocellular and cholangiocarcinoma. Oncogene 2006;25:3818–3822.

    Article  PubMed  CAS  Google Scholar 

  67. Uenishi T, Kubo S, Yamamoto T, Shuto T, Ogawa M, Tanaka H, et al. Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence. Cancer Sci 2003;94:851–857.

    Article  PubMed  CAS  Google Scholar 

  68. Chiang DY, Villanueva A, Hoshida Y, Peix J, Newell P, Minguez B, et al. A novel molecular classification of HCV-related hepatocellular carcinoma (HCC) based on integrative genomic analysis. J Hepatol 2008;48(S2):S12, EASL 2008.

    Article  Google Scholar 

  69. Tanabe KK, Lemoine A, Finkelstein DM, Kawasaki H, Fujii T, Chung RT, et al. Epidermal growth factor gene functional polymorphism and the risk of hepatocellular carcinoma in patients with cirrhosis. JAMA 2008;299:53–60.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Digestive Health Center of Excellence, University of Virginia Health System, P.O. Box 800708, Charlottesville, VA, 22908-0708, USA

    Stephen Caldwell

  2. Hallym University Medical Center, Seoul, Korea

    Sang H. Park

Authors
  1. Stephen Caldwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sang H. Park
    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

Caldwell, S., Park, S.H. The epidemiology of hepatocellular cancer: from the perspectives of public health problem to tumor biology. J Gastroenterol 44 (Suppl 19), 96–101 (2009). https://doi.org/10.1007/s00535-008-2258-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-008-2258-6

Key words

Search

Navigation