1. Villanueva A. Hepatocellular carcinoma. Engl J Med 2019;380:1450-62.

2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.

3. Forner A, Reig M, Bruix J. Hepatocellular carcinoma. Lancet 2018;391:1301-14.

4. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 2019;16:589-604.

5. El-Serag HB, Tran T, Everhart JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology 2004;126:460-8.

6. N’Kontchou G, Paries J, Htar MTT, Ganne-Carrie N, Costentin L, et al. Risk factors for hepatocellular carcinoma in patients with alcoholic or viral C cirrhosis. Clin Gastroenterol Hepatol 2006;4:1062-8.

7. Zaman SN, Melia WM, Johnson RD, Portmann BC, Johnson PJ, et al. Risk factors in development of hepatocellular carcinoma in cirrhosis: prospective study of 613 patients. Lancet 1985;1:1357-60.

8. Yu MW, Chang HC, Liaw YF, Lin SM, Lee SD, et al. Familial risk of hepatocellular carcinoma among chronic hepatitis B carriers and their relatives. J Natl Cancer Inst 2000;92:1159-64.

9. Hemminki K, Li X. Familial liver and gall bladder cancer: a nationwide epidemiological study from Sweden. Gut 2003;52:592-6.

10. Rich NE, Hester C, Odewole M, Murphy CC, Parikh ND, et al. Racial and ethnic differences in presentation and outcomes of hepatocellular carcinoma. Clin Gastroenterol Hepatol 2019;17:551-9.e1.

11. Herbst DA, Reddy KR. Risk factors for hepatocellular carcinoma. Clin Liver Dis 2012;1:180-2.

12. Stickel F, Schuppan D, Hahn EG, Seitz HK. Cocarcinogenic effects of alcohol in hepatocarcinogenesis. Gut 2002;51:132-9.

13. Ganne-Carrié N, Chaffaut C, Bourcier V, Archambeaud I, Perarnau JM, et al. Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis. J Hepatol 2018;69:1274-83.

14. Morgan TR, Mandayam S, Jamal MM. Alcohol and hepatocellular carcinoma. Gastroenterology 2004;127:S87-96.

15. Roerecke M, Vafaei A, Hasan OSM, Chrystoja BR, Cruz M, et al. Alcohol consumption and risk of liver cirrhosis: a systematic review and meta-analysis. Am J Gastroenterol 2019;114:1574-86.

16. Grewal P, Viswanathen VA. Liver cancer and alcohol. Clin Liver Dis 2012;16:839-50.

17. Ganne-Carrié N, Nahon P. Hepatocellular carcinoma in the setting of alcohol-related liver disease. J Hepatol 2019;70:284-93.

18. Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, 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;3:1683-91.

19. Heckley GA, Jarl J, Asamoah BO, G-Gerdtham U. How the risk of liver cancer changes after alcohol cessation: a review and meta-analysis of the current literature. BMC Cancer 2011;11:446.

20. Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 2011;141:1572-85.

21. Jean-Frédéric B, Adelaide D, Marie-Quitterie P, Aline M, Caroline B, et al. Diabetes, HBV infection and smoking are independent risk factors for developing hepatocellular carcinoma on non-fibrotic liver in the NoFLIC French multicenter case-control study. Hepatology 2015;62:276A.

22. Costentin CE, Mourad A, Lahmek P, Causse X, Pariente A, et al. Hepatocellular carcinoma is diagnosed at a later stage in alcoholic patients: results of a prospective, nationwide study. Cancer 2018;124:1964-72.

23. Bucci L, Garuti F, Camelli V, Lenzi B, Farinati F, et al; Italian Liver Cancer (ITA.LI.CA) Group; Italian Liver Cancer ITA LI CA Group. Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome. Aliment Pharmacol Ther 2016;43:385-99.

24. Kumar R, Goh BBG, Kam JW, Chang PE, Tan CK. Comparisons between non-alcoholic steatohepatitis and alcohol-related hepatocellular carcinoma. Clin Mol Hepatol 2020;26:196-208.

25. EASL. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol 2018;69:182-236.

26. Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 2018;68:723-50.

27. Andersson KL, Salomon JA, Goldie SJ, Chung RT. Cost effectiveness of alternative surveillance strategies for hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol 2008;6:1418-24.

28. Bolondi L, Sofia S, Siringo S, Gaiani S, Casali A, et al. Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis. Gut 2001;48:251-9.

29. Singal AG, Lampertico P, Nahon P. Epidemiology and surveillance for hepatocellular carcinoma: new trends. J Hepatol 2020;72:250-61.

30. Singal AG, Yopp AC, Gupta S, Skinner CS, Halm EA, et al. Failure rates in the hepatocellular carcinoma surveillance process. Cancer Prev Res (Phila) 2012;5:1124-30.

31. Thursz M, Gual A, Lackner C, Mathurin P, Moreno C, et al. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease. J Hepatol 2018;69:154-81.

32. Teschke R. Alcoholic liver disease: alcohol metabolism, cascade of molecular mechanisms, cellular targets, and clinical aspects. Biomedicines 2018;6:106.

33. Seitz HK, Stickel F. Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress. Biol Chem 2006;387:349-60.

34. Stickel F, Hampe J. Genetic determinants of alcoholic liver disease. Gut 2012;61:150-9.

35. Stickel F, Osterreicher CH. The role of genetic polymorphisms in alcoholic liver disease. Alcohol Alcohol 2006;41:209-24.

36. Homann N, Stickel F, Konig IR, Jacobs A, Junghanns K, et al. Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers. Int J Cancer 2006;118:1998-2002.

37. Seitz HK, Stickel F. Molecular mechanisms of alcohol mediated carcinogenesis. Nat Rev 2007;7:599-612.

38. Dasgupta A. Genetic polymorphisms of alcohol metabolizing enzymes associated with protection from or increased risk of alcohol abuse. Alcohol, Drugs, Genes and the Clinical Laboratory 2017:107-16.

39. Abul-Husn NS, Cheng X, Li AH, Xin Y, Schurmann C, et al. A protein-truncating HSD17B13 variant and protection from chronic liver disease. Engl J Med 2018;378:1096-106.

40. Buch S, Stickel F, Trepo E, Way M, Herrmann A, et al. A genome-wide association study confirms PNPLA3 and identifies TM6SF2 and MBOAT7 as risk loci for alcohol-related cirrhosis. Nat Genet 2015;47:1443-8.

41. Tian C, Stokowski RP, Kershenobich D, Ballinger DG, Hinds DA. Variant in PNPLA3 is associated with alcoholic liver disease. Nat Genet 2010;42:21-3.

42. Trepo E, Guyot E, Ganne-Carrie N, Degre D, Gustot T, et al. PNPLA3 (rs738409 C>G) is a common risk variant associated with hepatocellular carcinoma in alcoholic cirrhosis. Hepatology 2012;55:1307-8.

43. Salameh H, Raff E, Erwin A, Seth D, Nischalke HD, et al. PNPLA3 gene polymorphism is associated with predisposition to and severity of alcoholic liver disease. Am J Gastroenterol 2015;110:846-56.

44. Falleti E, Cussigh A, Cmet S, Fabris C, Toniutto P. PNPLA3 rs738409 and TM6SF2 rs58542926 variants increase the risk of hepatocellular carcinoma in alcoholic cirrhosis. Dig Liver Dis 2016;48:69-75.

45. Seth D, Daly AK, Haber PS, Day CP. Patatin-like phospholipase domain containing 3: a case in point linking genetic susceptibility for alcoholic and nonalcoholic liver disease. Hepatology 2010;51:1463-5.

46. Trépo E, Nahon P, Bontempi G, Valenti L, Falleti E, et al. Association between the PNPLA3 (rs738409 C\textgreaterG) variant and hepatocellular carcinoma: Evidence from a meta-analysis of individual participant data. Hepatology 2014;59.

47. Chen JH, Wang YY, Lv WB, Gan Y, Chang W, et al. Effects of interactions between environmental factors and KIF1B genetic variants on the risk of hepatocellular carcinoma in a Chinese cohort. World J Gastroenterol 2016;22:4183-90.

48. Nahon P, Cao Q, Guyot E, Rufat P, Sutton A, et al. O054 TM6SF2-T and PNPLA3-G genetic variants co-modulate the risk of hepatocellular carcinoma in caucasian patients with alcoholic cirrhosis. Inter-cohort validation in 1068 patients. J Hepatol 2015;62:S218-9.

49. Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, et al. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat Genet 2011;43:1131-8.

50. Stickel F, Lutz P, Buch S, Nischalke HD, Silva I, et al. Genetic variation in HSD17B13 reduces the risk of developing cirrhosis and hepatocellular carcinoma in alcohol misusers. Hepatology 2019. epub ahead of print. doi: 10.1002/hep.30996

51. Thursz M, Kamath PS, Mathurin P, Szabo G, Shah VH. Alcohol-related liver disease: Areas of consensus, unmet needs and opportunities for further study. J Hepatol 2019;70:521-30.

52. Yang J, Trépo E, Nahon P, Cao Q, Moreno C, et al. PNPLA3 and TM6SF2 variants as risk factors of hepatocellular carcinoma across various etiologies and severity of underlying liver diseases. Int J Cancer 2019;144:533-44.

53. Guyot E, Sutton A, Rufat P, Laguillier C, Mansouri A, et al. PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis. J Hepatol 2013;58:312-8.

54. Kerr TA, Korenblat KM, Davidson NO. MicroRNAs and liver disease. Transl Res 2011;157:241-52.

55. Xu RH, Wei W, Krawczyk M, Wang W, Luo H, et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat Mater 2017;16:1155-61.

56. Yu JH, Suh YJ, Jin YJ, Yeo NY, Jang JW, et al. Prediction model for hepatocellular carcinoma risk in treatment-naive chronic hepatitis B patients receiving entecavir/tenofovir. Eur J Gastroenterol Hepatol 2019;31:865-72.

57. Whitfield JB, Schwantes-An TH, Cordell HJ, Darlay R, Masson S, et al. Can genotyping predict risk of alcohol-related cirrhosis in high-risk drinkers? Hepatology 2019;70:171A-2.

58. Anstee QM, Day CP. The genetics of nonalcoholic fatty liver disease: spotlight on PNPLA3 and TM6SF2. Semin Liver Dis 2015;35:270-90.

59. Anstee QM, Seth D, Day CP. Genetic factors that affect risk of alcoholic and nonalcoholic fatty liver disease. Gastroenterology 2016;150:1728-44.e7.

60. Torkamani A, Wineinger NE, Topol EJ. The personal and clinical utility of polygenic risk scores. Nat Rev Genet 2018;19:581-90.

61. Maas P, Barrdahl M, Joshi AD, Auer PL, Gaudet MM, et al. Breast cancer risk from modifiable and nonmodifiable risk factors among white women in the United States. JAMA Oncol 2016;2:1295-302.

62. Lee A, Mavaddat N, Wilcox AN, Cunningham AP, Carver T, et al. BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors. Genet Med 2019;21:1708-18.

63. Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2015;26:v8-30.

64. Stickel F, Buch S, Nischalke HD, Weiss KH, Gotthardt D, et al. Genetic variants in PNPLA3 and TM6SF2 predispose to the development of hepatocellular carcinoma in individuals with alcohol-related cirrhosis. Am J Gastroenterol 2018;113:1475-83.

65. Scaggiante B, Kazemi M, Pozzato G, Dapas B, Farra R, et al. Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials. World J Gastroenterol 2014;20:1268-88.

66. Shang S, Plymoth A, Ge S, Feng Z, Rosen HR, et al. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology 2011:483-90.

67. Sieghart W, Wang X, Schmid K, Pinter M, König F, et al. Osteopontin expression predicts overall survival after liver transplantation for hepatocellular carcinoma in patients beyond the Milan criteria. J Hepatol 2011;54:89-97.

68. Zhou SL, Zhou ZJ, Hu ZQ, Song CL, Luo YJ, et al. Genomic sequencing identifies WNK2 as a driver in hepatocellular carcinoma and a risk factor for early recurrence. J Hepatol 2019;71:1152-63.

69. Niu ZS, Niu XJ, Wang WH. Genetic alterations in hepatocellular carcinoma: an update. World J Gastroenterol 2016;22:9069-95.

70. Ye QH, Qin LX, Forgues M, He P, Kim JW, et al. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med 2003;9:416-23.

71. Wahid B, Ali A, Rafiqe S, Idrees M. New insights into the epigenetics of hepatocellular carcinoma. Biomed Res Int 2017;2017:1609575.

72. Toh TB, Lim JJ, Chow EK. Epigenetics of hepatocellular carcinoma. Clin Trans Med 2019;8:13.

73. Lozano-Rosas MG, Chávez E, Aparicio-Cadena AR, Velasco-Loyden G, Sánchez VC. Mitoepigenetics and hepatocellular carcinoma. Hepatoma Res 2018;4:19.

74. Méndez-Sánchez N, Valencia-Rodríguez A, Vera-Barajas A, Abenavoli L, Scarpellini E, et al. The mechanism of dysbiosis in alcoholic liver disease leading to liver cancer. Hepatoma Res 2020;6:5.

75. Neuman MG, Seitz HK, French SW, Malnick S, Tsukamoto H, et al. Alcoholic-hepatitis, links to brain and microbiome: mechanisms, clinical and experimental research. Biomedicines 2020;8:63.

76. Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2016;2:16018.

77. Sia D, Jiao Y, Martinez-Quetglas I, Kuchuk O, Villacorta-Martin C, et al. Identification of an immune-specific class of hepatocellular carcinoma, based on molecular features. Gastroenterology 2017;153:812-26.

78. Wheelar DA, Roberts LR. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell 2017;169:1327-41.e23.

79. Calderaro J, Couchy G, Imbeaud S, Amaddeo G, Letouze E, et al. Histological subtypes of hepatocellular carcinoma are related to gene mutations and molecular tumour classification. J Hepatol 2017;67:727-38.

80. Harding JJ, Nandakumar S, Armenia J, Khalil DN, Albano M, et al. Prospective genotyping of hepatocellular carcinoma: clinical implications of next-generation sequencing for matching patients to targeted and immune therapies. Clin Cancer Res 2019;25:2116-26.

81. Theise ND. Histopathology of alcoholic liver disease. Clin Liver Dis 2013;2:64-7.

82. Lackner C, Tiniakos D. Fibrosis and alcohol-related liver disease. J Hepatol 2019;70:294-304.

83. Ganne-Carrie N, Layese R, Bourcier V, Cagnot C, Marcellin P, et al. Nomogram for individualized prediction of hepatocellular carcinoma occurrence in hepatitis C virus cirrhosis (ANRS CO12 CirVir). Hepatology 2016;64:1136-47.

84. Wong VW, Janssen HL. Can we use HCC risk scores to individualize surveillance in chronic hepatitis B infection? J Hepatol 2015;63:722-32.

85. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018;67:358-80.

86. Fujiwara N, Friedman SL, Goossens N, Hoshida Y. Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. J Hepatol 2018;68:526-49.

87. Kraft P, Wacholder S, Cornelis MC, Hu FB, Hayes RB, et al. Beyond odds ratios--communicating disease risk based on genetic profiles. Nat Rev Genet 2009;10:264-9.

88. Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J, et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res 2019;47:D1005-12.

89. Sugrue LP, Desikan RS. What are polygenic scores and why are they important? JAMA 2019;321:1820.

90. Wojcik GL, Graff M, Nishimura KK, Tao R, Haessler J, et al. Genetic analyses of diverse populations improves discovery for complex traits. Nature 2019;570:514-8.

91. Nakagawa S, Wei L, Song WM, Higashi T, Ghoshal S, et al. Molecular liver cancer prevention in cirrhosis by organ transcriptome analysis and lysophosphatidic acid pathway inhibition. Cancer Cell 2016;30:879-90.

92. DiMartini A, Day N, Dew MA, Javed L, Fitzgerald MG, et al. Alcohol consumption patterns and predictors of use following liver transplantation for alcoholic liver disease. Liver Transpl 2006;12:813-20.

93. Stickel F, Moreno C, Hampe J, Morgan MY. The genetics of alcohol dependence and alcohol-related liver disease. J Hepatol 2017;66:195-211.

94. Bjornsson E, Olsson J, Rydell A, Fredriksson K, Eriksson C, et al. Long-term follow-up of patients with alcoholic liver disease after liver transplantation in Sweden: impact of structured management on recidivism. Scand J Gastroenterol 2005;40:206-16.

95. Im GY, Cameron AM, Lucey MR. Liver transplantation for alcoholic hepatitis. J Hepatol 2019;70:328-34.

96. Hunter DJ, Drazen JM. Has the genome granted our wish yet? Engl J Med 2019;380:2391-3.

97. Schork AJ, Schork MA, Schork NJ. Genetic risks and clinical rewards. Nat Genet 2018;50:1210-1.

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