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Digestive Diseases and Sciences

, Volume 64, Issue 4, pp 903–909 | Cite as

Changing Epidemiology of HCC: How to Screen and Identify Patients at Risk?

  • Naomi Lange
  • Jean-François DufourEmail author
Review

Abstract

The prognosis of patients with hepatocellular carcinoma is dependent on the stage of tumor at diagnosis. The earlier the tumor is found, the higher the chances to offer a curative treatment. In order to diagnose hepatocellular carcinoma early, patients at risk should be enrolled in a surveillance program. The population at risk is usually defined as patients with cirrhosis. These patients should have twice a year a ultrasonographic examination of the liver. However, more and more patients will develop hepatocellular carcinoma in the context of nonalcoholic fatty liver disease which is tightly linked to obesity and diabetes. In these patients, this approach is jeopardized by the difficulty to perform a sonography of good quality due to the obesity and more importantly by the fact that hepatocellular carcinoma occurs frequently in the context of nonalcoholic fatty liver disease before the cirrhosis. This article reviews the impact of the changing epidemiology of hepatocellular carcinoma on its screening.

Keywords

Hepatocellular carcinoma Liver cancer Surveillance Population at risk Epidemiology 

Notes

Compliance with ethical standards

Conflict of interest

Naomi Lange do not have any conflicts of interest to disclose. Jean-François Dufour served as advisory committees in Abbvie, Bayer, BMS, Falk, Genfit, Genkyotex, Gilead Science, Intercept, Lilly, Novartis.

References

  1. 1.
    Fitzmaurice C, Akinyemiju TF, Al Lami FH. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016: a systematic analysis for the global Burden of disease study. JAMA Oncol. 2018;4:1553–1568.CrossRefGoogle Scholar
  2. 2.
    Altekruse SF, Devesa SS, Dickie LA, McGlynn KA, Kleiner DE. Histological classification of liver and intrahepatic bile duct cancers in SEER registries. J Registry Manag. 2011;38:201–205.Google Scholar
  3. 3.
    Akinyemiju T, 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.CrossRefGoogle Scholar
  4. 4.
    World Health Organisation Global Hepatitis Report 2017. 2017.Google Scholar
  5. 5.
    Jemal A, Ward EM, Johnson CJ, et al. Annual report to the nation on the status of cancer, 1975–2014, featuring survival. J Natl Cancer Inst. 2017;109(9):djx030.CrossRefGoogle Scholar
  6. 6.
    Parikh ND, Singal AG, Hutton DW. Cost effectiveness of regorafenib as second-line therapy for patients with advanced hepatocellular carcinoma. Cancer. 2017;123:3725–3731.CrossRefGoogle Scholar
  7. 7.
    Singal AG, Mittal S, Yerokun OA, et al. Hepatocellular carcinoma screening associated with early tumor detection and improved survival among patients with cirrhosis in the US. Am J Med. 2017;130:1099.e1–1106.e1.CrossRefGoogle Scholar
  8. 8.
    Al Hasani F, Knoepfli M, Gemperli A, et al. Factors affecting screening for hepatocellular carcinoma. Ann Hepatol. 2014;13:204–210.Google Scholar
  9. 9.
    Sapisochin G, Bruix J. Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches. Nat Rev Gastroenterol Hepatol. 2017;14:203–217.CrossRefGoogle Scholar
  10. 10.
    GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:1545–1602.CrossRefGoogle Scholar
  11. 11.
    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;  https://doi.org/10.1002/hep.30161.Google Scholar
  12. 12.
    Wong MC, Jiang JY, Goggins WB, et al. International incidence and mortality trends of liver cancer: a global profile. Sci Rep. 2017;7:45846.CrossRefGoogle Scholar
  13. 13.
    Petrick JL, Kelly SP, Altekruse SF, McGlynn KA, Rosenberg PS. Future of hepatocellular carcinoma incidence in the United States forecast through 2030. J Clin Oncol. 2016;34:1787–1794.CrossRefGoogle Scholar
  14. 14.
    Valery PC, Laversanne M, Clark PJ, Petrick JL, McGlynn KA, Bray F. Projections of primary liver cancer to 2030 in 30 countries worldwide. Hepatology. 2017;  https://doi.org/10.1002/hep.29498.Google Scholar
  15. 15.
    Flemming JA, Kim W, Brosgart CL, Terrault NA. Reduction in liver transplant wait-listing in the era of direct-acting antiviral therapy. Hepatology. 2017;65:804–812.CrossRefGoogle Scholar
  16. 16.
    EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64:1388–402. Google Scholar
  17. 17.
    Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018;67:123–133.CrossRefGoogle Scholar
  18. 18.
    Estes C, Anstee QM, Arias-Loste MT, et al. Modeling NAFLD disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016–2030. J Hepatol. 2018;69:896–904.CrossRefGoogle Scholar
  19. 19.
    Ansaldi F, Orsi A, Sticchi L, Icardi G. Hepatitis C virus in the new era: perspectives in epidemiology, prevention, diagnostics and predictors of response to therapy. World J Gastroenterol. 2014;20:9633–9652.CrossRefGoogle Scholar
  20. 20.
    El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264.e1–1273.e1.Google Scholar
  21. 21.
    Tanaka Y, Kurbanov F, Mano S, et al. Molecular tracing of the global hepatitis C virus epidemic predicts regional patterns of hepatocellular carcinoma mortality. Gastroenterology. 2006;130:703–714.CrossRefGoogle Scholar
  22. 22.
    Tanaka Y, Hanada K, Orito E, et al. Molecular evolutionary analyses implicate injection treatment for schistosomiasis in the initial hepatitis C epidemics in Japan. J Hepatol. 2005;42:47–53.CrossRefGoogle Scholar
  23. 23.
    Tanaka H, Imai Y, Hiramatsu N, et al. Declining incidence of hepatocellular carcinoma in Osaka, Japan, from 1990 to 2003. Ann Intern Med. 2008;148:820–826.CrossRefGoogle Scholar
  24. 24.
    Chang MH, You SL, Chen CJ, et al. Long-term effects of hepatitis B immunization of infants in preventing liver cancer. Gastroenterology. 2016;151:472.e1–480.e1.Google Scholar
  25. 25.
    Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395.CrossRefGoogle Scholar
  26. 26.
    Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40:1461–1465.CrossRefGoogle Scholar
  27. 27.
    Liu YL, Patman GL, Leathart JB, et al. Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma. J Hepatol. 2014;61:75–81.CrossRefGoogle Scholar
  28. 28.
    Prorok PC. Epidemiologic approach for cancer screening. Problems in design and analysis of trials. Am J Pediatr Hematol Oncol. 1992;14:117–128.CrossRefGoogle Scholar
  29. 29.
    EASL Clinical Practice Guidelines. Management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.CrossRefGoogle Scholar
  30. 30.
    Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018;67:358–380.CrossRefGoogle Scholar
  31. 31.
    Sarasin FP, Giostra E, Hadengue A. Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis. Am J Med. 1996;101:422–434.CrossRefGoogle Scholar
  32. 32.
    Mittal S, Kanwal F, Ying J, et al. Effectiveness of surveillance for hepatocellular carcinoma in clinical practice: a United States cohort. J Hepatol. 2016;65:1148–1154.CrossRefGoogle Scholar
  33. 33.
    Costentin CE, Layese R, Bourcier V, et al. Compliance with hepatocellular carcinoma surveillance guidelines associated with increased lead-time adjusted survival of patients with compensated viral cirrhosis: a multi-center cohort study. Gastroenterology. 2018;155:431.e10–442.e10.CrossRefGoogle Scholar
  34. 34.
    Moon AM, Weiss NS, Beste LA, et al. No association between screening for hepatocellular carcinoma and reduced cancer-related mortality in patients with cirrhosis. Gastroenterology. 2018;155:1128.e6–1139.e6.CrossRefGoogle Scholar
  35. 35.
    Tzartzeva K, Obi J, Rich NE, et al. Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis. Gastroenterology. 2018;154:1706.e1–1718.e1.CrossRefGoogle Scholar
  36. 36.
    Mourad A, Deuffic-Burban S, Ganne-Carrié N, et al. Hepatocellular carcinoma screening in patients with compensated hepatitis C virus (HCV)-related cirrhosis aware of their HCV status improves survival: a modeling approach. Hepatology. 2014;59:1471–1481.CrossRefGoogle Scholar
  37. 37.
    Atiq O, Tiro J, Yopp AC, et al. An assessment of benefits and harms of hepatocellular carcinoma surveillance in patients with cirrhosis. Hepatology. 2017;65:1196–1205.CrossRefGoogle Scholar
  38. 38.
    Singal AG, Tiro J, Li X, Adams-Huet B, Chubak J. Hepatocellular carcinoma surveillance among patients with cirrhosis in a population-based integrated health care delivery system. J Clin Gastroenterol. 2017;51:650–655.CrossRefGoogle Scholar
  39. 39.
    Goossens N, Singal AG, King LY, et al. Cost-effectiveness of risk score-stratified hepatocellular carcinoma screening in patients with cirrhosis. Clin Transl Gastroenterol. 2017;8:e101.CrossRefGoogle Scholar
  40. 40.
    Cohen JD, Li L, Wang Y, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018;359:926–930.CrossRefGoogle Scholar
  41. 41.
    Tsukuma H, Hiyama T, Tanaka S, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993;328:1797–1801.CrossRefGoogle Scholar
  42. 42.
    Sangiovanni A, Prati GM, Fasani P, et al. The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients. Hepatology. 2006;43:1303–1310.CrossRefGoogle Scholar
  43. 43.
    Mancebo A, González-Diéguez ML, Cadahía V, et al. Annual incidence of hepatocellular carcinoma among patients with alcoholic cirrhosis and identification of risk groups. Clin Gastroenterol Hepatol. 2013;11:95–101.CrossRefGoogle Scholar
  44. 44.
    Mair RD, Valenzuela A, Ha NB, et al. Incidence of hepatocellular carcinoma among US patients with cirrhosis of viral or nonviral etiologies. Clin Gastroenterol Hepatol. 2012;10:1412–1417.CrossRefGoogle Scholar
  45. 45.
    Ioannou GN, Splan MF, Weiss NS, McDonald GB, Beretta L, Lee SP. Incidence and predictors of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2007;5(8):938–945.e4.CrossRefGoogle Scholar
  46. 46.
    Fattovich G, et al. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127:S35–S50.CrossRefGoogle Scholar
  47. 47.
    Ripoll C, Groszmann RJ, Garcia-Tsao G, et al. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis. J Hepatol. 2009;50:923–928.CrossRefGoogle Scholar
  48. 48.
    Lok AS, Seeff LB, Morgan TR, et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology. 2009;136:138–148.CrossRefGoogle Scholar
  49. 49.
    Trevisani F, Santi V, Gramenzi A, et al. Surveillance for early diagnosis of hepatocellular carcinoma: is it effective in intermediate/advanced cirrhosis? Am J Gastroenterol. 2007;102:2448–2457. (quiz 2458).CrossRefGoogle Scholar
  50. 50.
    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(1):73–84.CrossRefGoogle Scholar
  51. 51.
    Raffetti E, Fattovich G, Donato F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: a systematic review and meta-analysis. Liver Int. 2016;36:1239–1251.CrossRefGoogle Scholar
  52. 52.
    Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am J Gastroenterol. 2012;107:811–826.CrossRefGoogle Scholar
  53. 53.
    Piscaglia F, Svegliati-Baroni G, Barchetti A, et al. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: a multicenter prospective study. Hepatology. 2016;63:827–838.CrossRefGoogle Scholar
  54. 54.
    Mittal S, El-Serag HB, Sada YH, et al. Hepatocellular carcinoma in the absence of cirrhosis in united states veterans is associated with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2016;14:124.e1–131.e1.CrossRefGoogle Scholar
  55. 55.
    Duan XY, Qiao L, Fan JG. Clinical features of nonalcoholic fatty liver disease-associated hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int. 2012;11:18–27.CrossRefGoogle Scholar
  56. 56.
    Mohamad B, Shah V, Onyshchenko M, et al. Characterization of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis. Hepatol Int. 2016;10:632–639.CrossRefGoogle Scholar
  57. 57.
    Mittal S, Sada YH, El-Serag HB, et al. Temporal trends of nonalcoholic fatty liver disease-related hepatocellular carcinoma in the veteran affairs population. Clin Gastroenterol Hepatol. 2015;13:594.e1–601.e1.CrossRefGoogle Scholar
  58. 58.
    Yu MW, Lin CL, Liu CJ, Yang SH, Tseng YL, Wu CF. Influence of metabolic risk factors on risk of hepatocellular carcinoma and liver-related death in men with chronic hepatitis B: a large cohort study. Gastroenterology. 2017;153(4):1006–1017.e5.CrossRefGoogle Scholar
  59. 59.
    Hassan MM, Abdel-Wahab R, Kaseb A, et al. Obesity early in adulthood increases risk but does not affect outcomes of hepatocellular carcinoma. Gastroenterology. 2015;149:119–129.CrossRefGoogle Scholar
  60. 60.
    Ganne-Carrié N, Chaffaut C, Bourcier V, et al. Estimate of hepatocellular carcinoma’s incidence in patients with alcoholic cirrhosis. J Hepatol. 2018;69:1274–1283.CrossRefGoogle Scholar
  61. 61.
    Turati F, Galeone C, Rota M, et al. Alcohol and liver cancer: a systematic review and meta-analysis of prospective studies. Ann Oncol. 2014;25:1526–1535.CrossRefGoogle Scholar
  62. 62.
    Hassan MM, Hwang LY, Hatten CJ, et al. Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology. 2002;36:1206–1213.CrossRefGoogle Scholar
  63. 63.
    Yuan JM, Govindarajan S, Arakawa K, Yu MC. Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S. Cancer. 2004;101:1009–1017.CrossRefGoogle Scholar
  64. 64.
    El-Serag HB, Kanwal F, Richardson P, Kramer J. Risk of hepatocellular carcinoma after sustained virological response in veterans with hepatitis C virus infection. Hepatology. 2016;64:130–137.CrossRefGoogle Scholar
  65. 65.
    Kanwal F, Kramer J, Asch SM, Chayanupatkul M, Cao Y, El-Serag HB. Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents. Gastroenterology. 2017;153:996.e1–1005.e1.CrossRefGoogle Scholar
  66. 66.
    Ioannou GN, Green PK, Beste LA, Mun EJ, Kerr KF, Berry K. Development of models estimating the risk of hepatocellular carcinoma after antiviral treatment for Hepatitis C. J Hepatol. 2018;69:1088–1098.CrossRefGoogle Scholar
  67. 67.
    Ganne-Carrie N, Layese R, Bourcier V, et al. Nomogram for individualized prediction of hepatocellular carcinoma occurrence in hepatitis C virus cirrhosis (ANRS CO12 CirVir). Hepatology. 2016;64:1136–1147.CrossRefGoogle Scholar
  68. 68.
    Nahon P, Layese R, Bourcier V, et al. Incidence of hepatocellular carcinoma after direct antiviral therapy for HCV in patients with cirrhosis included in surveillance programs. Gastroenterology. 2018;155(5):1436–1450.e6.CrossRefGoogle Scholar
  69. 69.
    Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008;48:335–352.CrossRefGoogle Scholar
  70. 70.
    Levrero M, Zucman-Rossi J. Mechanisms of HBV-induced hepatocellular carcinoma. J Hepatol. 2016;64:S84–s101.CrossRefGoogle Scholar
  71. 71.
    Chu YJ, Yang HI, Wu HC, et al. Aflatoxin B1 exposure increases the risk of cirrhosis and hepatocellular carcinoma in chronic hepatitis B virus carriers. Int J Cancer. 2017;141:711–720.CrossRefGoogle Scholar
  72. 72.
    Bressac B, Kew M, Wands J, Ozturk M. Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature. 1991;350:429–431.CrossRefGoogle Scholar
  73. 73.
    Chen C, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73.CrossRefGoogle Scholar
  74. 74.
    Yang H-I, Lu SN, Liaw YF, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347:168–174.CrossRefGoogle Scholar
  75. 75.
    Tseng TC, Liu CJ, Chen CL, et al. Risk stratification of hepatocellular carcinoma in hepatitis B virus e antigen-negative carriers by combining viral biomarkers. J Infect Dis. 2013;208:584–593.CrossRefGoogle Scholar
  76. 76.
    Romeo R, Del Ninno E, Rumi M, et al. A 28-year study of the course of hepatitis Delta infection: a risk factor for cirrhosis and hepatocellular carcinoma. Gastroenterology. 2009;136:1629–1638.CrossRefGoogle Scholar
  77. 77.
    Matsumoto A, Tanaka E, Rokuhara A, et al. Efficacy of lamivudine for preventing hepatocellular carcinoma in chronic hepatitis B: a multicenter retrospective study of 2795 patients. Hepatol Res. 2005;32:173–184.CrossRefGoogle Scholar
  78. 78.
    Papatheodoridis GV, Idilman R, Dalekos GN, et al. The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B. Hepatology. 2017;66:1444–1453.CrossRefGoogle Scholar
  79. 79.
    Papatheodoridis GV, Sypsa V, Dalekos G, et al. Eight-year survival in chronic hepatitis B patients under long-term entecavir or tenofovir therapy is similar to the general population. J Hepatol. 2018;68:1129–1136.CrossRefGoogle Scholar
  80. 80.
    Kim JH, Sinn DH, Kang W, et al. Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment. Hepatology. 2017;66:335–343.CrossRefGoogle Scholar

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

Authors and Affiliations

  1. 1.Department of General Internal MedicineInselspital-Bern University HospitalBernSwitzerland
  2. 2.Hepatology, Department of Visceral Surgery and MedicineInselspital-Bern University HospitalBernSwitzerland
  3. 3.Department of Biomedical ResearchUniversity of BernBernSwitzerland

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