Digestive Diseases and Sciences

, Volume 64, Issue 4, pp 910–917 | Cite as

Disease Burden of Hepatocellular Carcinoma: A Global Perspective

  • Mehmet Sayiner
  • Pegah Golabi
  • Zobair M. YounossiEmail author


Liver cancer is one of the leading causes of cancer-related mortality around the world. Hepatocellular carcinoma (HCC) is the primary cancer of the liver, accounting for the majority of liver cancers. The risk factors associated with HCC include chronic infections with HBV and HCV, alcoholic liver disease, and nonalcoholic fatty liver disease. Additionally, male patients have higher risk for than females, and the risk increases with older age. Mortality rates for HCC parallel its increasing incidence rates. In this context, incidence rate for HCC shows geographic variations in different parts of the world and is heavily affected by regional differences in risk factor for liver disease. The highest incidence rates for HCC are observed in Asia and Africa, while Europe and North America have lower rates. In fact, HBV is still regarded as the leading cause of HCC globally, while HCV is the most common cause of HCC in the USA. Recently, it has been suggested that HCC cases related to nonalcoholic fatty liver disease is on the rise, while the proportion of HCC attributed to alcoholic liver disease remains stable.


Hepatocellular carcinoma Epidemiology Hepatitis B Hepatitis C 


Compliance with ethical standards

Conflict of interest

Dr. Younossi is a consultant to BMS, Gilead, AbbVie, Intercept, NovoNordisk, Viking, Terns and Quest. All other authors have no conflict of interest to disclose.


  1. 1.
    World Health Organisation, News room, fact sheets, cancer. In: WHO [Internet]. 1 Feb 2018 [cited 6 May 2018].
  2. 2.
    Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47:S2–S6.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012;379:1245–1255.CrossRefPubMedGoogle Scholar
  4. 4.
    Alazawi W, Cunningham M, Dearden J, Foster GR. Systematic review: outcome of compensated cirrhosis due to chronic hepatitis C infection. Aliment Pharmacol Ther. 2010;32:344–355.CrossRefPubMedGoogle Scholar
  5. 5.
    Llovet JM, Bustamante J, Castells A, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology. 1999;29:62–67.CrossRefPubMedGoogle Scholar
  6. 6.
    Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–E386.CrossRefPubMedGoogle Scholar
  7. 7.
    El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365:1118–1127.CrossRefPubMedGoogle Scholar
  8. 8.
    Ryerson AB, Eheman CR, Altekruse SF, et al. Annual Report to the Nation on the Status of Cancer, 1975–2012, featuring the increasing incidence of liver cancer. Cancer. 2016;122:1312–1337.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Younossi ZM, Otgonsuren M, Henry L, et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology. 2015;62:1723–1730.CrossRefGoogle Scholar
  10. 10.
    Younossi Z, Stepanova M, Ong JP, et al. Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates. Clin Gastroenterol Hepatol. 2018;. Scholar
  11. 11.
    McGlynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis. 2015;19:223–238.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    McGlynn KA, London WT. Epidemiology and natural history of hepatocellular carcinoma. Best Pract Res Clin Gastroenterol. 2005;19:3–23.CrossRefPubMedGoogle Scholar
  13. 13.
    Bray F, Ferlay J, Laversanne M, et al. Cancer incidence in five continents: inclusion criteria, highlights from volume X and the global status of cancer registration. Int J Cancer. 2015;137:2060–2071.CrossRefPubMedGoogle Scholar
  14. 14.
    Mitchell T, Armstrong GL, Hu DJ, Wasley A, Painter JA. The increasing burden of imported chronic hepatitis B—United States, 1974–2008. PLoS ONE. 2011;6:e27717.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Kim D, Li AA, Perumpail BJ, et al. Changing trends in etiology- and ethnicity-based annual mortality rates of cirrhosis and hepatocellular carcinoma in the United States. Hepatology. 2018;. Scholar
  16. 16.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  17. 17.
    Naugler WE, Sakurai T, Kim S, et al. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 2007;317:121–124.CrossRefPubMedGoogle Scholar
  18. 18.
    Global Burden of Disease Liver Cancer Collaboration, Akinyemiju T, Abera S, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol. 2017;3:1683–1691.CrossRefPubMedCentralGoogle Scholar
  19. 19.
    Chen C-J, Wang L-Y, Yu M-W. Epidemiology of hepatitis B virus infection in the Asia-Pacific region. J Gastroenterol Hepatol. 2000;15:E36. Scholar
  20. 20.
    Bhaumik P. Epidemiology of viral hepatitis and liver diseases in India. Euroasian J Hepatogastroenterol. 2015;5:34–36.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014;61:S45–S57.CrossRefPubMedGoogle Scholar
  22. 22.
    Wild CP, Gong YY. Mycotoxins and human disease: a largely ignored global health issue. Carcinogenesis. 2010;31:71–82.CrossRefPubMedGoogle Scholar
  23. 23.
    Groopman JD, Kensler TW, Wild CP. Protective interventions to prevent aflatoxin-induced carcinogenesis in developing countries. Annu Rev Public Health. 2008;29:187–203.CrossRefPubMedGoogle Scholar
  24. 24.
    Fan J-H, Wang J-B, Jiang Y, et al. Attributable causes of liver cancer mortality and incidence in china. Asian Pac J Cancer Prev. 2013;14:7251–7256.CrossRefPubMedGoogle Scholar
  25. 25.
    Umemura T, Ichijo T, Yoshizawa K, Tanaka E, Kiyosawa K. Epidemiology of hepatocellular carcinoma in Japan. J Gastroenterol. 2009;44:102–107.CrossRefPubMedGoogle Scholar
  26. 26.
    Vongsuvanh R, van der Poorten D, George J. Nonalcoholic fatty liver disease-related hepatocellular carcinoma: a sleeping tiger in the Asia Pacific. Hepatol Int. 2013;7:823–832.CrossRefPubMedGoogle Scholar
  27. 27.
    Sun Z, Chen T, Thorgeirsson SS, et al. Dramatic reduction of liver cancer incidence in young adults: 28 year follow-up of etiological interventions in an endemic area of China. Carcinogenesis. 2013;34:1800–1805.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Bridges JFP, Dong L, Gallego G, Blauvelt BM, Joy SM, Pawlik TM. Prioritizing strategies for comprehensive liver cancer control in Asia: a conjoint analysis. BMC Health Serv Res. 2012;12:376.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Toyoda H, Kumada T, Tada T, Sone Y, Kaneoka Y, Maeda A. Characteristics and prognosis of patients with hepatocellular carcinoma after the year 2000 in Japan. J Gastroenterol Hepatol. 2011;26:1765–1771.CrossRefPubMedGoogle Scholar
  30. 30.
    Chimed T, Sandagdorj T, Znaor A, et al. Cancer incidence and cancer control in Mongolia: results from the National Cancer Registry 2008–12. Int J Cancer. 2017;140:302–309.CrossRefGoogle Scholar
  31. 31.
    Liu Y, Wu F. Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment. Environ Health Perspect. 2010;118:818–824.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Ladep NG. Why is the tumour different in Africa. Clinical dilemmas in primary liver cancer. Hoboken: Wiley; 2011:11–17.CrossRefGoogle Scholar
  33. 33.
    Tognarelli J, Ladep NG, Crossey MME, et al. Reasons why West Africa continues to be a hotbed for hepatocellular carcinoma. Niger Med J. 2015;56:231–235.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Mokdad AA, Lopez AD, Shahraz S, et al. Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. BMC Med. 2014;12:145.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Kew MC. Epidemiology of hepatocellular carcinoma in sub-Saharan Africa. Ann Hepatol. 2013;12:173–182.CrossRefGoogle Scholar
  36. 36.
    Yang JD, Mohamed EA, Aziz AOA, et al. Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa Liver Cancer Consortium. Lancet Gastroenterol Hepatol. 2017;2:103–111.CrossRefPubMedGoogle Scholar
  37. 37.
    Spearman CW, Sonderup MW. Health disparities in liver disease in sub-Saharan Africa. Liver Int. 2015;35:2063–2071.CrossRefPubMedGoogle Scholar
  38. 38.
    Ascione A, Fontanella L, Imparato M, Rinaldi L, De Luca M. Mortality from cirrhosis and hepatocellular carcinoma in Western Europe over the last 40 years. Liver Int. 2017;37:1193–1201.CrossRefPubMedGoogle Scholar
  39. 39.
    Blachier M, Leleu H, Peck-Radosavljevic M, Valla D-C, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013;58:593–608.CrossRefGoogle Scholar
  40. 40.
    Taylor-Robinson SD, Toledano MB, Arora S, et al. Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales 1968–1998. Gut. 2001;48:816–820.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    West J, Wood H, Logan RFA, Quinn M, Aithal GP. Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001. Br J Cancer. 2006;94:1751.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Ladep NG, Khan SA, Crossey MM, Thillainayagam AV, Taylor-Robinson SD, Toledano MB. Incidence and mortality of primary liver cancer in England and Wales: changing patterns and ethnic variations. World J Gastroenterol. 2014;20:1544–1553.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Bertuccio P, Bosetti C, Levi F, Decarli A, Negri E, La Vecchia C. A comparison of trends in mortality from primary liver cancer and intrahepatic cholangiocarcinoma in Europe. Ann Oncol. 2013;24:1667–1674.CrossRefPubMedGoogle Scholar
  44. 44.
    Bosetti C, Levi F, Boffetta P, Lucchini F, Negri E, La Vecchia C. Trends in mortality from hepatocellular carcinoma in Europe, 1980–2004. Hepatology. 2008;48:137–145.CrossRefPubMedGoogle Scholar
  45. 45.
    Santi V, Buccione D, Di Micoli A, et al. The changing scenario of hepatocellular carcinoma over the last two decades in Italy. J Hepatol. 2012;56:397–405.CrossRefPubMedGoogle Scholar
  46. 46.
    Pinter M, Hucke F, Zielonke N, Trauner M, Sieghart W, Peck-Radosavljevic M. Epidemiological trends of hepatocellular carcinoma in Austria. Dig Dis. 2014;32:664–669.CrossRefPubMedGoogle Scholar
  47. 47.
    Schütte K, Kipper M, Kahl S, et al. Clinical characteristics and time trends in etiology of hepatocellular cancer in Germany. Digestion. 2013;87:147–159.CrossRefPubMedGoogle Scholar
  48. 48.
    Sherman M. Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis. 2005;25:143–154.CrossRefPubMedGoogle Scholar
  49. 49.
    Golabi P, Jeffers T, Younoszai Z, et al. Independent predictors of mortality and resource utilization in viral hepatitis related hepatocellular carcinoma. Ann Hepatol. 2017;16:555–564.CrossRefGoogle Scholar
  50. 50.
    Zhu AX. Current status of hepatocellular carcinoma in the United States. Chin Clin Oncol. 2013;2:45.PubMedGoogle Scholar
  51. 51.
    Altekruse SF, Henley SJ, Cucinelli JE, McGlynn KA. Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol. 2014;109:542–553.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Espey DK, Wu X-C, Swan J, et al. Annual report to the nation on the status of cancer, 1975–2004, featuring cancer in American Indians and Alaska Natives. Cancer. 2007;110:2119–2152.CrossRefPubMedGoogle Scholar
  53. 53.
    El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–1273.e1.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Nordenstedt H, White DL, El-Serag HB. The changing pattern of epidemiology in hepatocellular carcinoma. Dig Liver Dis. 2010;42:S206–S214.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Golabi P, Fazel S, Otgonsuren M, Sayiner M, Locklear CT, Younossi ZM. Mortality assessment of patients with hepatocellular carcinoma according to underlying disease and treatment modalities. Medicine. 2017;96:e5904.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Sayiner M, Wymer M, Golabi P, Ford J, Srishord I, Younossi ZM. Presence of hepatitis C (HCV) infection in Baby Boomers with Medicare is independently associated with mortality and resource utilisation. Aliment Pharmacol Ther. 2016;43:1060–1068.CrossRefPubMedGoogle Scholar
  57. 57.
    Turner BJ, Taylor BS, Hanson JT, et al. Implementing hospital-based baby boomer hepatitis C virus screening and linkage to care: strategies, results, and costs. J Hosp Med. 2015;10:510–516.CrossRefPubMedGoogle Scholar
  58. 58.
    Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64:73–84.CrossRefPubMedGoogle Scholar
  59. 59.
    Sayiner M, Koenig A, Henry L, Younossi ZM. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in the United States and the rest of the world. Clin Liver Dis. 2016;20:205–214.CrossRefPubMedGoogle Scholar
  60. 60.
    Kachuri L, De P, Ellison LF, Semenciw R, Advisory Committee on Canadian Cancer Statistics. Cancer incidence, mortality and survival trends in Canada, 1970–2007. Chronic Dis Inj Can. 2013;33:69–80.PubMedGoogle Scholar
  61. 61.
    Jiang X, Pan SY, de Groh M, Liu S, Morrison H. Increasing incidence in liver cancer in Canada, 1972–2006: age-period-cohort analysis. J Gastrointest Oncol. 2011;2:223–231.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Chen Y, Yi Q, Mao Y. Cluster of liver cancer and immigration: a geographic analysis of incidence data for Ontario 1998–2002. Int J Health Geogr. 2008;7:28.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Ramírez-Soto MC, Ortega-Cáceres G, Cabezas C. Trends in mortality burden of hepatocellular carcinoma, cirrhosis, and fulminant hepatitis before and after roll-out of the first pilot vaccination program against hepatitis B in Peru: an analysis of death certificate data. Vaccine. 2017;35:3808–3812.CrossRefPubMedGoogle Scholar
  64. 64.
    Petrick JL, Braunlin M, Laversanne M, Valery PC, Bray F, McGlynn KA. International trends in liver cancer incidence, overall and by histologic subtype, 1978–2007. Int J Cancer. 2016;139:1534–1545.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Ha J, Chaudhri A, Avirineni A, Pan J-J. Burden of hepatocellular carcinoma among hispanics in South Texas: a systematic review. Biomark Res. 2017;5:15.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Luke C, Price T, Roder D. Epidemiology of cancer of the liver and intrahepatic bile ducts in an Australian population. Asian Pac J Cancer Prev. 2010;11:1479–1485.PubMedGoogle Scholar
  67. 67.
    Carville KS, MacLachlan JH, Thursfield V, Cowie BC. Hepatocellular carcinoma over three decades in Victoria, Australia: epidemiology, diagnosis and trends, 1984-2013. Intern Med J. 2018;48:835–844.CrossRefPubMedGoogle Scholar
  68. 68.
    Zhu RX, Seto W-K, Lai C-L, Yuen M-F. Epidemiology of hepatocellular carcinoma in the Asia-Pacific region. Gut Liver. 2016;10:332–339.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Wallace MC, Preen DB, Short MW, Adams LA, Jeffrey GP. Hepatocellular carcinoma in Australia 1982–2014: increasing incidence and improving survival. Liver Int. 2018;. Scholar
  70. 70.
    Waziry R, Grebely J, Amin J, et al. Trends in hepatocellular carcinoma among people with HBV or HCV notification in Australia (2000–2014). J Hepatol. 2016;65:1086–1093.CrossRefPubMedGoogle Scholar
  71. 71.
    Meredith I, Sarfati D, Ikeda T, Blakely T. Cancer in Pacific people in New Zealand. Cancer Causes Control. 2012;23:1173–1184.CrossRefPubMedGoogle Scholar
  72. 72.
    Bianchi G, Loguercio C, Sgarbi D, et al. Reduced quality of life of patients with hepatocellular carcinoma. Dig Liver Dis. 2003;35:46–54.CrossRefPubMedGoogle Scholar
  73. 73.
    Gandhi S, Khubchandani S, Iyer R. Quality of life and hepatocellular carcinoma. J Gastrointest Oncol. 2014;5:296–317.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Ahmed S, de Souza NN, Qiao W, Kasai M, Keem LJ, Shelat VG. Quality of life in hepatocellular carcinoma patients treated with transarterial chemoembolization. HPB Surg. 2016;2016:6120143.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Chie W-C, Blazeby JM, Hsiao C-F, et al. Differences in health-related quality of life between European and Asian patients with hepatocellular carcinoma. Asia Pac J Clin Oncol. 2017;13:e304–e311.CrossRefPubMedGoogle Scholar
  76. 76.
    Jin S, Yan L, Li B, et al. Quality of life and psychologic distress of recipients after adult living-donor liver transplantation (LDLT)—a study from mainland China. Transplant Proc. 2010;42:2611–2616.CrossRefPubMedGoogle Scholar
  77. 77.
    Lei JY, Yan LN, Wang WT, Zhu JQ, Li DJ. Health-related quality of life and psychological distress in patients with early-stage hepatocellular carcinoma after hepatic resection or transplantation. Transplant Proc. 2016;48:2107–2111.CrossRefPubMedGoogle Scholar
  78. 78.
    Sternby Eilard M, Hagström H, Mortensen KE, et al. Quality of life as a prognostic factor for survival in hepatocellular carcinoma. Liver Int. 2018;38:885–894.CrossRefPubMedGoogle Scholar
  79. 79.
    Li L, Mo FK, Chan SL, et al. Prognostic values of EORTC QLQ-C30 and QLQ-HCC18 index-scores in patients with hepatocellular carcinoma—clinical application of health-related quality-of-life data. BMC Cancer. 2017;17:8.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Mishra A, Otgonsuren M, Venkatesan C, Afendy M, Erario M, Younossi ZM. The inpatient economic and mortality impact of hepatocellular carcinoma from 2005 to 2009: analysis of the US nationwide inpatient sample. Liver Int. 2013;33:1281–1286.CrossRefPubMedGoogle Scholar
  81. 81.
    Jinjuvadia R, Salami A, Lenhart A, Jinjuvadia K, Liangpunsakul S, Salgia R. Hepatocellular carcinoma: a decade of hospitalizations and financial burden in the United States. Am J Med Sci. 2017;354:362–369.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Lang K, Danchenko N, Gondek K, Shah S, Thompson D. The burden of illness associated with hepatocellular carcinoma in the United States. J Hepatol. 2009;50:89–99.CrossRefPubMedGoogle Scholar
  83. 83.
    El Khoury AC, Klimack WK, Wallace C, Razavi H. Economic burden of hepatitis C-associated diseases in the United States. J Viral Hepat. 2012;19:153–160.CrossRefPubMedGoogle Scholar
  84. 84.
    Younossi ZM, Tanaka A, Eguchi Y, Henry L, Beckerman R, Mizokami M. Treatment of hepatitis C virus leads to economic gains related to reduction in cases of hepatocellular carcinoma and decompensated cirrhosis in Japan. J Viral Hepat. 2018;25:945–951.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Mehmet Sayiner
    • 1
    • 2
  • Pegah Golabi
    • 2
  • Zobair M. Younossi
    • 1
    • 2
    Email author
  1. 1.Department of Medicine, Center for Liver DiseasesInova Fairfax HospitalFalls ChurchUSA
  2. 2.Betty and Guy Beatty Center for Integrated ResearchInova Health SystemFalls ChurchUSA

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