Abdominal Radiology

, Volume 43, Issue 1, pp 13–25 | Cite as

Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis

  • An Tang
  • Oussama Hallouch
  • Victoria Chernyak
  • Aya Kamaya
  • Claude B. Sirlin


Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer mortality worldwide. Incidence rates of liver cancer vary widely between geographic regions and are highest in Eastern Asia and sub-Saharan Africa. In the United States, the incidence of HCC has increased since the 1980s. HCC detection at an early stage through surveillance and curative therapy has considerably improved the 5-year survival. Therefore, medical societies advocate systematic screening and surveillance of target populations at particularly high risk for developing HCC to facilitate early-stage detection. Risk factors for HCC include cirrhosis, chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), excess alcohol consumption, non-alcoholic fatty liver disease, family history of HCC, obesity, type 2 diabetes mellitus, and smoking. Medical societies utilize risk estimates to define target patient populations in which imaging surveillance is recommended (risk above threshold) or in which the benefits of surveillance are uncertain (risk unknown or below threshold). All medical societies currently recommend screening and surveillance in patients with cirrhosis and subsets of patients with chronic HBV; some societies also include patients with stage 3 fibrosis due to HCV as well as additional groups. Thus, target population definitions vary between regions, reflecting cultural, demographic, economic, healthcare priority, and biological differences. The Liver Imaging Reporting and Data System (LI-RADS) defines different patient populations for surveillance and for diagnosis and staging. We also discuss general trends pertaining to geographic region, age, gender, ethnicity, impact of surveillance on survival, mortality, and future trends.

Key words

Review article Hepatocellular carcinoma Epidemiology Risk factors Prevalence Incidence 



American Association for the Study of Liver Diseases


Asian Pacific Association for the Study of the Liver


European Association for the Study of the Liver-European Organization for Research and Treatment of Cancer


Hepatitis B virus


Hepatocellular carcinoma


Hepatitis C virus


Japan Society of Hepatology


Korean Liver Cancer Study Group and the National Cancer Center


Liver Imaging Reporting and Data System


Non-alcoholic fatty liver disease


Non-alcoholic steatohepatitis


World Health Organization


Compliance with Ethical Standards


This work was supported by a clinical research scholarship by the Fonds de recherche du Québec—Santé and Fondation de l’association des radiologistes du Québec (Career Award #26993) to An Tang.

Conflict of Interest

An Tang, Victoria Chernyak, Aya Kamaya and Claude B. Sirlin are members of the LI-RADS Steering Committee. Oussama Hallouch declares that he has no conflict of interest. Aya Kamaya receives royalties from Elsevier/Amirsys. Claude B. Sirlin has industry research grants from Bayer, Guerbet, Siemens, GE, Philips, Supersonic, and Arterys and consulting and service agreements with Alexion, AstraZeneca, Bioclinica, BMS, Bracco, Celgene, Fibrogen, Galmed, Genentech, Genzyme, Gilead, Icon, Intercept, Isis, Janssen, NuSirt, Perspectum, Pfizer, Profil, Sanofi, Shire, Synageva, Tobira, Takeda, and Virtual Scopics.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

IRB approval

No IRB approval was required for this review article.


  1. 1.
    Ferenci P, Fried M, Labrecque D, et al. (2010) Hepatocellular carcinoma (HCC): a global perspective. J Clin Gastroenterol 44(4):239–245. doi: 10.1097/MCG.0b013e3181d46ef2 CrossRefPubMedGoogle Scholar
  2. 2.
    El-Serag HB (2011) Hepatocellular carcinoma. N Engl J Med 365(12):1118–1127. doi: 10.1056/NEJMra1001683 CrossRefPubMedGoogle Scholar
  3. 3.
    International Agency for Research on Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. (2012). URL consulted on March 15, 2017:
  4. 4.
    El-Serag HB (2012) Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 142(6):1264–1273, e1261. doi: 10.1053/j.gastro.2011.12.061
  5. 5.
    Altekruse SF, McGlynn KA, Reichman ME (2009) Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol 27(9):1485–1491. doi: 10.1200/JCO.2008.20.7753 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat database: incidence—SEER 9 Regs research data, Nov 2009 Sub (1973–2007). Bethesda, MD: National Cancer Institute, April 2010.Google Scholar
  7. 7.
    Foundation CL (2013) Liver disease in Canada: A crisis in the making. Halifax: Foundation CLGoogle Scholar
  8. 8.
    The BMJ (2017) Chapter 2. Quantifying disease in populations. URL consulted on March 10, 2017:
  9. 9.
    Singal AG, El-Serag HB (2015) Hepatocellular carcinoma from epidemiology to prevention: Translating knowledge into practice. Clin Gastroenterol Hepatol 13(12):2140–2151. doi: 10.1016/j.cgh.2015.08.014 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Bruix J, Sherman M, American Association for the Study of Liver D (2011) Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022. doi: 10.1002/hep.24199 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    European Association For The Study Of The L, European Organisation For R, Treatment Of C (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56(4):908–943. doi: 10.1016/j.jhep.2011.12.001 CrossRefGoogle Scholar
  12. 12.
    Kudo M, Matsui O, Izumi N, et al. (2014) JSH consensus-based clinical practice guidelines for the management of hepatocellular carcinoma: 2014 Update by the Liver Cancer Study Group of Japan. Liver Cancer 3(3–4):458–468. doi: 10.1159/000343875 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Kudo M, Izumi N, Kokudo N, et al. (2011) Management of hepatocellular carcinoma in Japan: Consensus-based clinical practice guidelines proposed by the Japan Society of Hepatology (JSH) 2010 updated version. Dig Dis 29(3):339–364. doi: 10.1159/000327577 CrossRefPubMedGoogle Scholar
  14. 14.
    Omata M, Lesmana LA, Tateishi R, et al. (2010) Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 4(2):439–474. doi: 10.1007/s12072-010-9165-7 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Korean Liver Cancer Study G, National Cancer Center K (2015) 2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma. Korean J Radiol: Off J Korean Radiol Soc 16(3):465–522. doi: 10.3348/kjr.2015.16.3.465 CrossRefGoogle Scholar
  16. 16.
    American College of Radiology (2017) Liver Imaging Reporting and Data System. Latest version retrieved from
  17. 17.
    An Tang, Kathryn J. Fowler, Victoria Chernyak, William C. Chapman, Claude B. Sirlin (2017) LI-RADS and transplantation for hepatocellular carcinoma. Abdom Radiol. doi: 10.1007/s00261-017-1210-8
  18. 18.
    Vilgrain V, Lewin M, Vons C, et al. (1999) Hepatic nodules in Budd-Chiari syndrome: imaging features. Radiology 210(2):443–450. doi: 10.1148/radiology.210.2.r99fe13443 CrossRefPubMedGoogle Scholar
  19. 19.
    Flor N, Zuin M, Brovelli F, et al. (2010) Regenerative nodules in patients with chronic Budd-Chiari syndrome: a longitudinal study using multiphase contrast-enhanced multidetector CT. Eur J Radiol 73(3):588–593. doi: 10.1016/j.ejrad.2009.01.012 CrossRefPubMedGoogle Scholar
  20. 20.
    Reshamwala PA, Kleiner DE, Heller T (2006) Nodular regenerative hyperplasia: not all nodules are created equal. Hepatology 44(1):7–14. doi: 10.1002/hep.21258 CrossRefPubMedGoogle Scholar
  21. 21.
    Fattovich G, Stroffolini T, Zagni I, Donato F (2004) Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 127(5 Suppl 1):S35–S50CrossRefPubMedGoogle Scholar
  22. 22.
    Theise ND (1996) Cirrhosis and hepatocellular neoplasia: more like cousins than like parent and child. Gastroenterology 111(2):526–528CrossRefPubMedGoogle Scholar
  23. 23.
    Yang JD, Kim WR, Coelho R, et al. (2011) Cirrhosis is present in most patients with hepatitis B and hepatocellular carcinoma. Clin Gastroenterol Hepatol 9(1):64–70. doi: 10.1016/j.cgh.2010.08.019 CrossRefPubMedGoogle Scholar
  24. 24.
    Colombo M, de Franchis R, Del Ninno E, et al. (1991) Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med 325(10):675–680. doi: 10.1056/NEJM199109053251002 CrossRefPubMedGoogle Scholar
  25. 25.
    Budhu A, Wang XW (2006) The role of cytokines in hepatocellular carcinoma. J Leukoc Biol 80(6):1197–1213. doi: 10.1189/jlb.0506297 CrossRefPubMedGoogle Scholar
  26. 26.
    Zucman-Rossi J, Villanueva A, Nault JC, Llovet JM (2015) Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology 149(5):1226–1239. doi: 10.1053/j.gastro.2015.05.061 CrossRefPubMedGoogle Scholar
  27. 27.
    World Health Organization (2016) Hepatitis B fact sheet. URL consulted on March 10, 2017:
  28. 28.
    Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ (2015) Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet 386(10003):1546–1555. doi: 10.1016/S0140-6736(15)61412-X CrossRefPubMedGoogle Scholar
  29. 29.
    Mittal S, El-Serag HB (2013) Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol 47(Suppl):S2–S6. doi: 10.1097/MCG.0b013e3182872f29 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Parkin DM (2006) The global health burden of infection-associated cancers in the year 2002. Int J Cancer 118(12):3030–3044. doi: 10.1002/ijc.21731 CrossRefPubMedGoogle Scholar
  31. 31.
    Shi J, Zhu L, Liu S, Xie WF (2005) A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China. Br J Cancer 92(3):607–612. doi: 10.1038/sj.bjc.6602333 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Fattovich G, Bortolotti F, Donato F (2008) Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 48(2):335–352. doi: 10.1016/j.jhep.2007.11.011 CrossRefPubMedGoogle Scholar
  33. 33.
    Lemon SM, McGivern DR (2012) Is hepatitis C virus carcinogenic? Gastroenterology 142(6):1274–1278. doi: 10.1053/j.gastro.2012.01.045 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    World Health Organization (2016) Hepatitis C fact sheet. URL consulted on March 10, 2017:
  35. 35.
    Tanaka Y, Kurbanov F, Mano S, et al. (2006) Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality. Gastroenterology 130(3):703–714. doi: 10.1053/j.gastro.2006.01.032 CrossRefPubMedGoogle Scholar
  36. 36.
    Freeman AJ, Dore GJ, Law MG, et al. (2001) Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology 34(4 Pt 1):809–816. doi: 10.1053/jhep.2001.27831 CrossRefPubMedGoogle Scholar
  37. 37.
    Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW (2010) Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology 138 (2):513–521, 521 e511–516. doi: 10.1053/j.gastro.2009.09.067
  38. 38.
    El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132(7):2557–2576. doi: 10.1053/j.gastro.2007.04.061 CrossRefPubMedGoogle Scholar
  39. 39.
    Donato F, Tagger A, Gelatti U, et al. (2002) Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women. Am J Epidemiol 155(4):323–331CrossRefPubMedGoogle Scholar
  40. 40.
    Turati F, Galeone C, Rota M, et al. (2014) Alcohol and liver cancer: a systematic review and meta-analysis of prospective studies. Ann Oncol 25(8):1526–1535. doi: 10.1093/annonc/mdu020 CrossRefPubMedGoogle Scholar
  41. 41.
    La Vecchia C, Negri E, Cavalieri d’Oro L, Franceschi S (1998) Liver cirrhosis and the risk of primary liver cancer. Eur J Cancer Prev 7(4):315–320CrossRefPubMedGoogle Scholar
  42. 42.
    Yuan JM, Govindarajan S, Arakawa K, Yu MC (2004) Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S. Cancer 101(5):1009–1017. doi: 10.1002/cncr.20427 CrossRefPubMedGoogle Scholar
  43. 43.
    Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M (2015) Global epidemiology of non-alcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence and outcomes. Hepatology. doi: 10.1002/hep.28431
  44. 44.
    Welzel TM, Graubard BI, Zeuzem S, et al. (2011) Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-Medicare database. Hepatology 54(2):463–471. doi: 10.1002/hep.24397 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Sanyal A, Poklepovic A, Moyneur E, Barghout V (2010) Population-based risk factors and resource utilization for HCC: US perspective. Curr Med Res Opin 26(9):2183–2191. doi: 10.1185/03007995.2010.506375 CrossRefPubMedGoogle Scholar
  46. 46.
    Mittal S, El-Serag HB, Sada YH, Kanwal F, Duan Z, Temple S, May SB, Kramer JR, Richardson PA, Davila JA (2016) Hepatocellular carcinoma in the absence of cirrhosis in United States veterans is Associated with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 14(1):124–131 e121. doi: 10.1016/j.cgh.2015.07.019
  47. 47.
    Magnussen A, Parsi MA (2013) Aflatoxins, hepatocellular carcinoma and public health. World J Gastroenterol 19(10):1508–1512. doi: 10.3748/wjg.v19.i10.1508 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    McGlynn KA, Petrick JL, London WT (2015) Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis 19(2):223–238. doi: 10.1016/j.cld.2015.01.001 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Qian GS, Ross RK, Yu MC, et al. (1994) A follow-up study of urinary markers of aflatoxin exposure and liver cancer risk in Shanghai, People’s Republic of China. Cancer Epidemiol Biomarkers Prev 3(1):3–10PubMedGoogle Scholar
  50. 50.
    Ross RK, Yuan JM, Yu MC, et al. (1992) Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet 339(8799):943–946CrossRefPubMedGoogle Scholar
  51. 51.
    Fan JH, Wang JB, Jiang Y, et al. (2013) Attributable causes of liver cancer mortality and incidence in china. Asian Pac J Cancer Prev 14(12):7251–7256CrossRefPubMedGoogle Scholar
  52. 52.
    Yang Y, Wu QJ, Xie L, et al. (2014) Prospective cohort studies of association between family history of liver cancer and risk of liver cancer. Int J Cancer 135(7):1605–1614. doi: 10.1002/ijc.28792 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Elmberg M, Hultcrantz R, Ekbom A, et al. (2003) Cancer risk in patients with hereditary hemochromatosis and in their first-degree relatives. Gastroenterology 125(6):1733–1741CrossRefPubMedGoogle Scholar
  54. 54.
    Larsson SC, Wolk A (2007) Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer 97(7):1005–1008. doi: 10.1038/sj.bjc.6603932 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348(17):1625–1638. doi: 10.1056/NEJMoa021423 CrossRefPubMedGoogle Scholar
  56. 56.
    Weng CJ, Hsieh YH, Tsai CM, et al. (2010) Relationship of insulin-like growth factors system gene polymorphisms with the susceptibility and pathological development of hepatocellular carcinoma. Ann Surg Oncol 17(7):1808–1815. doi: 10.1245/s10434-009-0904-8 CrossRefPubMedGoogle Scholar
  57. 57.
    Park EJ, Lee JH, Yu GY, et al. (2010) Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140(2):197–208. doi: 10.1016/j.cell.2009.12.052 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Chen J, Han Y, Xu C, Xiao T, Wang B (2015) Effect of type 2 diabetes mellitus on the risk for hepatocellular carcinoma in chronic liver diseases: a meta-analysis of cohort studies. Eur J Cancer Prev 24(2):89–99. doi: 10.1097/CEJ.0000000000000038 CrossRefPubMedGoogle Scholar
  59. 59.
    Lee YC, Cohet C, Yang YC, et al. (2009) Meta-analysis of epidemiologic studies on cigarette smoking and liver cancer. Int J Epidemiol 38(6):1497–1511. doi: 10.1093/ije/dyp280 CrossRefPubMedGoogle Scholar
  60. 60.
    Humans IWGotEoCRt (2004) Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum 83:1–1438Google Scholar
  61. 61.
    Bosch FX, Ribes J, Diaz M, Cleries R (2004) Primary liver cancer: worldwide incidence and trends. Gastroenterology 127(5 Suppl 1):S5–S16CrossRefPubMedGoogle Scholar
  62. 62.
    McGavock JM, Victor RG, Unger RH, Szczepaniak LS (2006) Adiposity of the heart, revisited. Ann Internal Med 144(7):517–524CrossRefGoogle Scholar
  63. 63.
    Altekruse SF, Henley SJ, Cucinelli JE, McGlynn KA (2014) Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol 109(4):542–553. doi: 10.1038/ajg.2014.11 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Lopez PM, Villanueva A, Llovet JM (2006) Systematic review: evidence-based management of hepatocellular carcinoma–an updated analysis of randomized controlled trials. Aliment Pharmacol Ther 23(11):1535–1547. doi: 10.1111/j.1365-2036.2006.02932.x CrossRefPubMedGoogle Scholar
  65. 65.
    Sutherland LM, Williams JA, Padbury RT, et al. (2006) Radiofrequency ablation of liver tumors: a systematic review. Arch Surg 141(2):181–190. doi: 10.1001/archsurg.141.2.181 CrossRefPubMedGoogle Scholar
  66. 66.
    Singal AG, Pillai A, Tiro J (2014) Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis. PLoS Med 11(4):e1001624. doi: 10.1371/journal.pmed.1001624 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Zhang BH, Yang BH, Tang ZY (2004) Randomized controlled trial of screening for hepatocellular carcinoma. J Cancer Res Clin Oncol 130(7):417–422. doi: 10.1007/s00432-004-0552-0 CrossRefPubMedGoogle Scholar
  68. 68.
    Myers RP, Krajden M, Bilodeau M, et al. (2014) Burden of disease and cost of chronic hepatitis C infection in Canada. Can J Gastroenterol Hepatol 28(5):243–250CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Clark T, Maximin S, Meier J, Pokharel S, Bhargava P (2015) Hepatocellular carcinoma: review of epidemiology, screening, imaging diagnosis, response assessment, and treatment. Curr Probl Diagn Radiol 44(6):479–486. doi: 10.1067/j.cpradiol.2015.04.004 CrossRefPubMedGoogle Scholar
  70. 70.
    Lange CM, Jacobson IM, Rice CM, Zeuzem S (2014) Emerging therapies for the treatment of hepatitis C. EMBO Mol Med 6(1):4–15. doi: 10.1002/emmm.201303131 CrossRefPubMedGoogle Scholar
  71. 71.
    Beasley RP, Hwang LY, Lin CC, Chien CS (1981) Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet 2(8256):1129–1133CrossRefPubMedGoogle Scholar
  72. 72.
    Sherman M, Peltekian KM, Lee C (1995) Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology 22(2):432–438PubMedGoogle Scholar
  73. 73.
    Lok AS, Seeff LB, Morgan TR, et al. (2009) Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 136(1):138–148. doi: 10.1053/j.gastro.2008.09.014 CrossRefPubMedGoogle Scholar
  74. 74.
    Mancebo A, Gonzalez-Dieguez ML, Cadahia V, et al. (2013) Annual incidence of hepatocellular carcinoma among patients with alcoholic cirrhosis and identification of risk groups. Clin Gastroenterol Hepatol 11(1):95–101. doi: 10.1016/j.cgh.2012.09.007 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Radiology, Radio-Oncology and Nuclear MedicineUniversity of Montreal and CRCHUMMontréalCanada
  2. 2.Centre de recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM)MontrealCanada
  3. 3.Department of RadiologyMontefiore Medical CenterBronxUSA
  4. 4.Stanford University Medical CenterStanfordUSA
  5. 5.Liver Imaging Group, Department of RadiologyUniversity of California San DiegoLa JollaUSA

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