Epidemiology of Hepatocellular Carcinoma

  • Donna L. WhiteEmail author
  • Fasiha Kanwal
  • Li Jiao
  • Hashem B. El-Serag
Part of the Current Clinical Oncology book series (CCO)


Liver cancer is the second leading cause of cancer-related mortality resulting in 745,000 deaths annually worldwide. It is overwhelmingly manifest as hepatocellular carcinoma (HCC) arising in middle-aged and older adults. It is also largely a preventable disease. Globally, most cases are related to chronic hepatitis B virus (HBV) infection, and occur in sub-Saharan Africa and Eastern Asia (except Japan). In contrast, hepatitis C virus (HCV) is the leading cause in North America and Western Europe. Recent rapid increases in HCC rates have been observed in several Western populations (particularly in the U.S.) and largely parallel rapidly increasing rates of obesity and diabetes. Striking geographic and racial variations in HCC risk are also evident and likely predominantly due to known differences in the prevalence of major risk factors like HBV and HCV infections. Other established risk factors for HCC include older age, male sex, heavy alcohol intake, aflatoxin exposure, iron overload related to hemochromatosis, and possibly tobacco smoking. The role of diet is largely unknown; however, higher levels of caffeinated coffee consumption are consistently associated with decreased HCC risk across diverse viral and nonviral disease etiologies and populations. Host inherited genetic variation is also being increasingly examined in association with HCC risk, but definitive data are largely lacking. Overall, most HCC risk factors operate by promoting the development of cirrhosis which is primary precursor lesion in most cases. Once cirrhosis is established, the annual risk of HCC ranges between 1 and 7 % thereafter, with particularly increased risk of progression in males with chronic HCV infection. This review discusses in detail the epidemiology of liver cancer, and particularly of HCC, from a global perspective.


Sustained Virological Response Population Attributable Fraction Metabolic Syndrome Feature AFB1 Exposure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. GLOBOCAN 2012: cancer incidence and mortality, version 1.1. IARC Cancer Base ed. Lyon: IARC; 2014.Google Scholar
  2. 2.
    Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–128.PubMedCrossRefGoogle Scholar
  3. 3.
    McGlynn KA, Tsao L, Hsing AW, Devesa SS, Fraumeni JF Jr. International trends and patterns of primary liver cancer. Int J Cancer. 2001;94(2):290–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Okuda K, Nakanuma Y, Miyazaki M. Cholangiocarcinoma: recent progress. Part 1: epidemiology and etiology. J Gastroenterol Hepatol. 2002;17(10):1049–55.PubMedCrossRefGoogle Scholar
  5. 5.
    Sithithaworn P, Yongvanit P, Duenngai K, Kiatsopit N, Pairojkul C. Roles of liver fluke infection as risk factor for cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2014;21(5):301–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Kamsa-Ard S, Wiangnon S, Suwanrungruang K, Promthet S, Khuntikeo N, Kamsa-Ard S, et al. Trends in liver cancer incidence between 1985 and 2009, Khon Kaen, Thailand: cholangiocarcinoma. Asian Pac J Cancer Prev. 2011;12(9):2209–13.PubMedGoogle Scholar
  7. 7.
    Furst T, Duthaler U, Sripa B, Utzinger J, Keiser J. Trematode infections: liver and lung flukes. Infect Dis Clin North Am. 2012;26(2):399–419.PubMedCrossRefGoogle Scholar
  8. 8.
    Keiser J, Utzinger J. Food-borne trematodiases. Clin Microbiol Rev. 2009;22(3):466–83.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Furst T, Keiser J, Utzinger J. Global burden of human food-borne trematodiasis: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12(3):210–21.PubMedCrossRefGoogle Scholar
  10. 10.
    Chang MH, Chen CJ, Lai MS, Hsu HM, Wu TC, Kong MS, et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N Engl J Med. 1997;336(26):1855–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Wen WH, Chen HL, Ni YH, Hsu HY, Kao JH, Hu FC, et al. Secular trend of the viral genotype distribution in children with chronic hepatitis B virus infection after universal infant immunization. Hepatology. 2011;53(2):429–36.PubMedCrossRefGoogle Scholar
  12. 12.
    Chen JG, Egner PA, Ng D, Jacobson LP, Munoz A, Zhu YR, et al. Reduced aflatoxin exposure presages decline in liver cancer mortality in an endemic region of China. Cancer Prev Res (Phila). 2013;6(10):1038–45.CrossRefGoogle Scholar
  13. 13.
    Yu SZ. Primary prevention of hepatocellular carcinoma. J Gastroenterol Hepatol. 1995;10(6):674–82.PubMedCrossRefGoogle Scholar
  14. 14.
    El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557–76.PubMedCrossRefGoogle Scholar
  15. 15.
    United States Department of Health and Human Services CfDCaPaNCI. United States Cancer Statistics: 1999–2012. 2015.Google Scholar
  16. 16.
    IARC. Overall evaluations of carcinogenicity: an updating of IARC Monographs volumes 1 to 42. IARC Monogr Eval Carcinog Risks Hum Suppl. 1987;7:1–440.Google Scholar
  17. 17.
    IARC, Forman D, Bray F, Brewster DH, Gombe MC, Kohler B, Pinerson M et al. Cancer incidence in five continentsm, vol. X (electronic version). 2013. Lyon: International Agency for Research on Cancer.Google Scholar
  18. 18.
    Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013;47(Suppl):S2–6.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Scobie B, Woodfield DG, Fong R. Familial hepatocellular carcinoma and hepatitis B antigenemia in a New Zealand Chinese family. Aust N Z J Med. 1983;13(3):236–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Turati F, Edefonti V, Talamini R, Ferraroni M, Malvezzi M, Bravi F, et al. Family history of liver cancer and hepatocellular carcinoma. Hepatology. 2012;55(5):1416–25.PubMedCrossRefGoogle Scholar
  21. 21.
    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(4):542–53.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Kanwal F, Hoang T, Kramer JR, Asch SM, Goetz MB, Zeringue A, et al. Increasing prevalence of HCC and cirrhosis in patients with chronic hepatitis C virus infection. Gastroenterology. 2011;140(4):1182–8.PubMedCrossRefGoogle Scholar
  23. 23.
    White DL, Kanwal F, El-Serag HB. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review. Clin Gastroenterol Hepatol. 2012;10(12):1342–59.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    National Cancer Institute Surveillance EaERSP. SEER Stat Fact Sheets: Liver and Intrahepatic Bile Duct Cancer. 2015.Google Scholar
  25. 25.
    World Health Organization. Hepatitis: frequently asked questions. 2015.Google Scholar
  26. 26.
    Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;385(9963):117–171.Google Scholar
  27. 27.
    World Health Organization. Hepatitis B: Fact sheet No.204. 2015.Google Scholar
  28. 28.
    Thiele M, Gluud LL, Fialla AD, Dahl EK, Krag A. Large variations in risk of hepatocellular carcinoma and mortality in treatment naive hepatitis B patients: systematic review with meta-analyses. PLoS ONE. 2014;9(9):e107177.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Kao JH, Chen PJ, Lai MY, Chen DS. Genotypes and clinical phenotypes of hepatitis B virus in patients with chronic hepatitis B virus infection. J Clin Microbiol. 2002;40(4):1207–9.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Camma C, Giunta M, Andreone P, Craxi A. Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach. J Hepatol. 2001;34(4):593–602.PubMedCrossRefGoogle Scholar
  31. 31.
    Ebert G, Allison C, Preston S, Cooney J, Toe JG, Stutz MD, et al. Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis. Proc Natl Acad Sci U S A. 2015;112(18):5803–8.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis. 2002;2(8):479–86.PubMedCrossRefGoogle Scholar
  33. 33.
    Shi Y, Wu YH, Wu W, Zhang WJ, Yang J, Chen Z. Association between occult hepatitis B infection and the risk of hepatocellular carcinoma: a meta-analysis. Liver Int. 2012;32(2):231–40.PubMedCrossRefGoogle Scholar
  34. 34.
    Black AP, Nouanthong P, Nanthavong N, Souvannaso C, Vilivong K, Jutavijittum P, et al. Hepatitis B virus in the Lao People’s Democratic Republic: a cross sectional serosurvey in different cohorts. BMC Infect Dis. 2014;14:457.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Mohd HK, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013;57(4):1333–42.CrossRefGoogle Scholar
  36. 36.
    Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015;61(1):77–87.PubMedCrossRefGoogle Scholar
  37. 37.
    Global Health Observatory Data Repository 2015.Google Scholar
  38. 38.
    Benova L, Awad SF, Miller FD, Abu-Raddad LJ. Estimation of hepatitis C virus infections resulting from vertical transmission in Egypt. Hepatology. 2015;61(3):834–42.PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    Yoshizawa H. Hepatocellular carcinoma associated with hepatitis C virus infection in Japan: projection to other countries in the foreseeable future. Oncology. 2002;62(Suppl 1):8–17.PubMedCrossRefGoogle Scholar
  40. 40.
    Taura N, Fukushima N, Yastuhashi H, Takami Y, Seike M, Watanabe H, et al. The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased in Kyushu area. Med Sci Monit. 2011;17(2):H7–11.CrossRefGoogle Scholar
  41. 41.
    Armstrong GL, Alter MJ, McQuillan GM, Margolis HS. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology. 2000;31(3):777–82.PubMedCrossRefGoogle Scholar
  42. 42.
    Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology 2010; 138(2):513–21, 521.Google Scholar
  43. 43.
    Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349(9055):825–32.PubMedCrossRefGoogle Scholar
  44. 44.
    Freeman AJ, Dore GJ, Law MG, Thorpe M, Von OJ, Lloyd AR, et al. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology. 2001;34(4 Pt 1):809–16.PubMedCrossRefGoogle Scholar
  45. 45.
    El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142(6):1264–73.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Sherman KE, Rouster SD, Chung RT, Rajicic N. Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: a cross-sectional analysis of the US adult AIDS Clinical Trials Group. Clin Infect Dis. 2002;34(6):831–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Kanwal F, Kramer JR, Ilyas J, Duan Z, El-Serag HB. HCV genotype 3 is associated with an increased risk of cirrhosis and hepatocellular cancer in a national sample of U.S. Veterans with HCV. Hepatology 2014;60(1):98–105.Google Scholar
  48. 48.
    El-Serag HB, Kramer J, Duan Z, Kanwal F. Racial differences in the progression to cirrhosis and hepatocellular carcinoma in HCV-infected veterans. Am J Gastroenterol. 2014;109(9):1427–35.PubMedCrossRefGoogle Scholar
  49. 49.
    Welzel TM, Graubard BI, Quraishi S, Zeuzem S, Davila JA, El-Serag HB, et al. Population-attributable fractions of risk factors for hepatocellular carcinoma in the United States. Am J Gastroenterol. 2013;108(8):1314–21.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Alcohol consumption and ethyl carbamate. IARC Monogr Eval Carcinogenic Risks Hum 2010; 96:3–1383.Google Scholar
  51. 51.
    Li WQ, Park Y, McGlynn KA, Hollenbeck AR, Taylor PR, Goldstein AM, et al. Index-based dietary patterns and risk of incident hepatocellular carcinoma and mortality from chronic liver disease in a prospective study. Hepatology. 2014;60(2):588–97.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Adami HO, McLaughlin JK, Hsing AW, Wolk A, Ekbom A, Holmberg L, et al. Alcoholism and cancer risk: a population-based cohort study. Cancer Causes Control. 1992;3(5):419–25.PubMedCrossRefGoogle Scholar
  53. 53.
    Loomba R, Yang HI, Su J, Brenner D, Iloeje U, Chen CJ. Obesity and alcohol synergize to increase the risk of incident hepatocellular carcinoma in men. Clin Gastroenterol Hepatol 2010;8(10):891–8.Google Scholar
  54. 54.
    World Health Organization. Global status report on alcohol and health 2014. 2015.Google Scholar
  55. 55.
    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(6317):429–31.PubMedCrossRefGoogle Scholar
  56. 56.
    Lai H, Mo X, Yang Y, He K, Xiao J, Liu C, et al. Association between aflatoxin B1 occupational airway exposure and risk of hepatocellular carcinoma: a case-control study. Tumour Biol. 2014;35(10):9577–84.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Qian GS, Ross RK, Yu MC, Yuan JM, Gao YT, Henderson BE, et al. 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. 1994;3(1):3–10.PubMedGoogle Scholar
  58. 58.
    Yard EE, Daniel JH, Lewis LS, Rybak ME, Paliakov EM, Kim AA, et al. Human aflatoxin exposure in Kenya, 2007: a cross-sectional study. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2013;30(7):1322–31.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Asim M, Sarma MP, Thayumanavan L, Kar P. Role of aflatoxin B1 as a risk for primary liver cancer in north Indian population. Clin Biochem. 2011;44(14–15):1235–40.PubMedCrossRefGoogle Scholar
  60. 60.
    Yu MW, Lien JP, Chiu YH, Santella RM, Liaw YF, Chen CJ. Effect of aflatoxin metabolism and DNA adduct formation on hepatocellular carcinoma among chronic hepatitis B carriers in Taiwan. J Hepatol. 1997;27(2):320–30.PubMedCrossRefGoogle Scholar
  61. 61.
    Yu MW, Lien JP, Liaw YF, Chen CJ. Effects of multiple risk factors for hepatocellular carcinoma on formation of aflatoxin B1-DNA adducts. Cancer Epidemiol Biomarkers Prev. 1996;5(8):613–9.PubMedGoogle Scholar
  62. 62.
    Chen JG, Kensler TW. Changing rates for liver and lung cancers in Qidong. China. Chem Res Toxicol. 2014;27(1):3–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Wu HC, Wang Q, Yang HI, Ahsan H, Tsai WY, Wang LY, et al. Aflatoxin B1 exposure, hepatitis B virus infection, and hepatocellular carcinoma in Taiwan. Cancer Epidemiol Biomarkers Prev. 2009;18(3):846–53.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Liu Y, Chang CC, Marsh GM, Wu F. Population attributable risk of aflatoxin-related liver cancer: systematic review and meta-analysis. Eur J Cancer. 2012;48(14):2125–36.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Shirima CP, Kimanya ME, Kinabo JL, Routledge MN, Srey C, Wild CP, et al. Dietary exposure to aflatoxin and fumonisin among Tanzanian children as determined using biomarkers of exposure. Mol Nutr Food Res. 2013;57(10):1874–81.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Gong YY, Wilson S, Mwatha JK, Routledge MN, Castelino JM, Zhao B, et al. Aflatoxin exposure may contribute to chronic hepatomegaly in Kenyan school children. Environ Health Perspect. 2012;120(6):893–6.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Matumba L, Van PC, Ediage EN, De SS. Keeping mycotoxins away from the food: does the existence of regulations have any impact in Africa? Crit Rev Food Sci Nutr 2015.Google Scholar
  68. 68.
    Wu F, Guclu H. Aflatoxin regulations in a network of global maize trade. PLoS ONE. 2012;7(9):e45151.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Wu F, Stacy SL, Kensler TW. Global risk assessment of aflatoxins in maize and peanuts: are regulatory standards adequately protective? Toxicol Sci 2013;135(1):251–9.Google Scholar
  70. 70.
    El-Serag HB, Hampel H, Javadi F. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol. 2006;4(3):369–80.PubMedCrossRefGoogle Scholar
  71. 71.
    Tatsch E, Carvalho JA, Hausen BS, Bollick YS, Torbitz VD, Duarte T, et al. Oxidative DNA damage is associated with inflammatory response, insulin resistance and microvascular complications in type 2 diabetes. Mutat Res. 2015;782:17–22.PubMedCrossRefGoogle Scholar
  72. 72.
    Yao D, Brownlee M. Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands. Diabetes. 2010;59(1):249–55.PubMedCrossRefGoogle Scholar
  73. 73.
    Chen J, Han Y, Xu C, Xiao T, Wang B. 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. 2015;24(2):89–99.PubMedCrossRefGoogle Scholar
  74. 74.
    White DL, Ratziu V, El-Serag HB. Hepatitis C infection and risk of diabetes: a systematic review and meta-analysis. J Hepatol. 2008;49(5):831–44.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Chen HH, Lin MC, Muo CH, Yeh SY, Sung FC, Kao CH. Combination therapy of metformin and statin may decrease hepatocellular carcinoma among diabetic patients in Asia. Medicine (Baltimore). 2015;94(24):e1013.CrossRefGoogle Scholar
  76. 76.
    Chen HP, Shieh JJ, Chang CC, Chen TT, Lin JT, Wu MS, et al. Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies. Gut. 2013;62(4):606–15.PubMedCrossRefGoogle Scholar
  77. 77.
    Donadon V, Balbi M, Mas MD, Casarin P, Zanette G. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease. Liver Int. 2010;30(5):750–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Hassan MM, Curley SA, Li D, Kaseb A, Davila M, Abdalla EK, et al. Association of diabetes duration and diabetes treatment with the risk of hepatocellular carcinoma. Cancer. 2010;116(8):1938–46.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Zheng L, Yang W, Wu F, Wang C, Yu L, Tang L, et al. Prognostic significance of AMPK activation and therapeutic effects of metformin in hepatocellular carcinoma. Clin Cancer Res. 2013;19(19):5372–80.PubMedCrossRefGoogle Scholar
  80. 80.
    Li J, Hernanda PY, Bramer WM, Peppelenbosch MP, van LJ, Pan Q. Anti-tumor effects of metformin in animal models of hepatocellular carcinoma: a systematic review and meta-analysis. PLoS One 2015;10(6):e0127967.Google Scholar
  81. 81.
    Singh S, Singh PP, Singh AG, Murad MH, Sanchez W. Anti-diabetic medications and the risk of hepatocellular cancer: a systematic review and meta-analysis. Am J Gastroenterol. 2013;108(6):881–91.PubMedCrossRefGoogle Scholar
  82. 82.
    Nakagawa H, Umemura A, Taniguchi K, Font-Burgada J, Dhar D, Ogata H, et al. ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell. 2014;26(3):331–43.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013;499(7456):97–101.PubMedCrossRefGoogle Scholar
  84. 84.
    Larsson SC, Wolk A. Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer. 2007;97(7):1005–8.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Schlesinger S, Aleksandrova K, Pischon T, Fedirko V, Jenab M, Trepo E, et al. Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort. Int J Cancer. 2013;132(3):645–57.PubMedCrossRefGoogle Scholar
  86. 86.
    Woodford RM, Burton PR, O’Brien PE, Laurie C, Brown WA. Laparoscopic adjustable gastric banding in patients with unexpected cirrhosis: safety and outcomes. Obes Surg. 2015;25(10):1858–62.PubMedCrossRefGoogle Scholar
  87. 87.
    Nobili V, Alisi A, Grimaldi C, Liccardo D, Francalanci P, Monti L et al. Non-alcoholic fatty liver disease and hepatocellular carcinoma in a 7-year-old obese boy: coincidence or comorbidity? Pediatr Obes 2014;9(5):e99–e102.Google Scholar
  88. 88.
    Berentzen TL, Gamborg M, Holst C, Sorensen TI, Baker JL. Body mass index in childhood and adult risk of primary liver cancer. J Hepatol. 2014;60(2):325–30.PubMedCrossRefGoogle Scholar
  89. 89.
    Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274–85.PubMedCrossRefGoogle Scholar
  90. 90.
    Younossi ZM, Otgonsuren M, Henry L, Venkatesan C, Mishra A, Erario M et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology 2015.Google Scholar
  91. 91.
    Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2011;140(1):124–31.PubMedCrossRefGoogle Scholar
  92. 92.
    Adams LA, Lindor KD. Nonalcoholic fatty liver disease. Ann Epidemiol. 2007;17(11):863–9.PubMedCrossRefGoogle Scholar
  93. 93.
    Afzali A, Berry K, Ioannou GN. Excellent posttransplant survival for patients with nonalcoholic steatohepatitis in the United States. Liver Transpl. 2012;18(1):29–37.PubMedCrossRefGoogle Scholar
  94. 94.
    Wattacheril J, Chalasani N. Nonalcoholic fatty liver disease (NAFLD): is it really a serious condition? Hepatology 2012;56(4):1580–4.Google Scholar
  95. 95.
    Groopman JD, Zhu JQ, Donahue PR, Pikul A, Zhang LS, Chen JS, et al. Molecular dosimetry of urinary aflatoxin-DNA adducts in people living in Guangxi Autonomous Region People’s Republic of China. Cancer Res. 1992;52(1):45–52.PubMedGoogle Scholar
  96. 96.
    Ashtari S, Pourhoseingholi MA, Zali MR. Non-alcohol fatty liver disease in Asia: prevention and planning. World J Hepatol. 2015;7(13):1788–96.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Meyer J, Rohrmann S, Bopp M, Faeh D. Impact of smoking and excess body weight on overall and site-specific cancer mortality risk. Cancer Epidemiol Biomarkers Prev. 2015;24(10):1516–22.PubMedCrossRefGoogle Scholar
  98. 98.
    Chuang SC, Lee YC, Hashibe M, Dai M, Zheng T, Boffetta P. Interaction between cigarette smoking and hepatitis B and C virus infection on the risk of liver cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010;19(5):1261–8.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Trichopoulos D, Bamia C, Lagiou P, Fedirko V, Trepo E, Jenab M, et al. Hepatocellular carcinoma risk factors and disease burden in a European cohort: a nested case-control study. J Natl Cancer Inst. 2011;103(22):1686–95.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Fan JH, Wang JB, Jiang Y, Xiang W, Liang H, Wei WQ, et al. Attributable causes of liver cancer mortality and incidence in china. Asian Pac J Cancer Prev. 2013;14(12):7251–6.PubMedCrossRefGoogle Scholar
  101. 101.
    Maheshwari S, Sarraj A, Kramer J, El-Serag HB. Oral contraception and the risk of hepatocellular carcinoma. J Hepatol. 2007;47(4):506–13.PubMedCrossRefGoogle Scholar
  102. 102.
    McGlynn KA, Sahasrabuddhe VV, Campbell PT, Graubard BI, Chen J, Schwartz LM, et al. Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project. Br J Cancer. 2015;112(7):1266–72.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    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(6):1393–400.PubMedGoogle Scholar
  104. 104.
    Bravi F, Bosetti C, Tavani A, Gallus S, La VC. Coffee reduces risk for hepatocellular carcinoma: an updated meta-analysis. Clin Gastroenterol Hepatol. 2013;11(11):1413–21.PubMedCrossRefGoogle Scholar
  105. 105.
    Johnson S, Koh WP, Wang R, Govindarajan S, Yu MC, Yuan JM. Coffee consumption and reduced risk of hepatocellular carcinoma: findings from the Singapore Chinese Health Study. Cancer Causes Control. 2011;22(3):503–10.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Bamia C, Lagiou P, Jenab M, Trichopoulou A, Fedirko V, Aleksandrova K, et al. Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: multicentre, prospective cohort study. Int J Cancer. 2015;136(8):1899–908.PubMedCrossRefGoogle Scholar
  107. 107.
    Petrick JL, Freedman ND, Graubard BI, Sahasrabuddhe VV, Lai GY, Alavanja MC, et al. Coffee consumption and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma by sex: the Liver Cancer Pooling Project. Cancer Epidemiol Biomarkers Prev. 2015;24(9):1398–406.PubMedCrossRefGoogle Scholar
  108. 108.
    Aleksandrova K, Bamia C, Drogan D, Lagiou P, Trichopoulou A, Jenab M et al. The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 2015.Google Scholar
  109. 109.
    Torres DM, Harrison SA. Is it time to write a prescription for coffee? Coffee and liver disease. Gastroenterology. 2013;144(4):670–2.PubMedCrossRefGoogle Scholar
  110. 110.
    Yu F, Jin Z, Jiang H, Xiang C, Tang J, Li T, et al. Tea consumption and the risk of five major cancers: a dose-response meta-analysis of prospective studies. BMC Cancer. 2014;14:197.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Zhang YF, Xu Q, Lu J, Wang P, Zhang HW, Zhou L, et al. Tea consumption and the incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Eur J Cancer Prev. 2015;24(4):353–62.PubMedCrossRefGoogle Scholar
  112. 112.
    Huang X, Kojima-Yuasa A, Xu S, Norikura T, Kennedy DO, Hasuma T, et al. Green tea extract enhances the selective cytotoxic activity of Zizyphus jujuba extracts in HepG2 cells. Am J Chin Med. 2008;36(4):729–44.PubMedCrossRefGoogle Scholar
  113. 113.
    Huang YQ, Lu X, Min H, Wu QQ, Shi XT, Bian KQ et al. Green tea and liver cancer risk: a meta-analysis of prospective cohort studies in Asian populations. Nutrition 2015.Google Scholar
  114. 114.
    Yang Y, Zhang D, Feng N, Chen G, Liu J, Chen G, et al. Increased intake of vegetables, but not fruit, reduces risk for hepatocellular carcinoma: a meta-analysis. Gastroenterology. 2014;147(5):1031–42.PubMedCrossRefGoogle Scholar
  115. 115.
    Luo J, Yang Y, Liu J, Lu K, Tang Z, Liu P, et al. Systematic review with meta-analysis: meat consumption and the risk of hepatocellular carcinoma. Aliment Pharmacol Ther. 2014;39(9):913–22.PubMedCrossRefGoogle Scholar
  116. 116.
    Freedman ND, Cross AJ, McGlynn KA, Abnet CC, Park Y, Hollenbeck AR, et al. Association of meat and fat intake with liver disease and hepatocellular carcinoma in the NIH-AARP cohort. J Natl Cancer Inst. 2010;102(17):1354–65.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Duarte-Salles T, Fedirko V, Stepien M, Aleksandrova K, Bamia C, Lagiou P, et al. Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort. Int J Cancer. 2015;137(11):2715–28.PubMedCrossRefGoogle Scholar
  118. 118.
    Sawada N, Inoue M, Iwasaki M, Sasazuki S, Shimazu T, Yamaji T, et al. Consumption of n-3 fatty acids and fish reduces risk of hepatocellular carcinoma. Gastroenterology. 2012;142(7):1468–75.PubMedCrossRefGoogle Scholar
  119. 119.
    Sharp GB, Lagarde F, Mizuno T, Sauvaget C, Fukuhara T, Allen N, et al. Relationship of hepatocellular carcinoma to soya food consumption: a cohort-based, case-control study in Japan. Int J Cancer. 2005;115(2):290–5.PubMedCrossRefGoogle Scholar
  120. 120.
    Iso H, Kubota Y. Nutrition and disease in the Japan Collaborative Cohort Study for Evaluation of Cancer (JACC). Asian Pac J Cancer Prev. 2007;8(Suppl):35–80.PubMedGoogle Scholar
  121. 121.
    Kurahashi N, Inoue M, Iwasaki M, Tanaka Y, Mizokami M, Tsugane S. Isoflavone consumption and subsequent risk of hepatocellular carcinoma in a population-based prospective cohort of Japanese men and women. Int J Cancer. 2009;124(7):1644–9.PubMedCrossRefGoogle Scholar
  122. 122.
    Zhang W, Shu XO, Li H, Yang G, Cai H, Ji BT, et al. Vitamin intake and liver cancer risk: a report from two cohort studies in China. J Natl Cancer Inst. 2012;104(15):1173–81.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Donna L. White
    • 1
    • 2
    Email author
  • Fasiha Kanwal
    • 1
    • 2
  • Li Jiao
    • 1
  • Hashem B. El-Serag
    • 1
    • 2
  1. 1.Section of Gastroenterology and Hepatology, Section of Health Services ResearchBaylor College of MedicineHoustonUSA
  2. 2.Clinical Epidemiology and Comparative Effectiveness ProgramMichael E. DeBakey VA Health Services Research Center of InnovationHoustonUSA

Personalised recommendations