REFERENCES
1. Reig M, Marino Z, Perello C, Inarrairaegui M, Ribeiro A, Lens S, Diaz A, Vilana R, Darnell A, Varela M, Sangro B, Calleja JL, Forns X, Bruix J. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol 2016;65:719-26.
2. Lencioni R, Llovet JM, Han G, Tak WY, Yang J, Guglielmi A, Paik SW, Reig M, Kim DY, Chau GY, Luca A, Del Arbol LR, Leberre MA, Niu W, Nicholson K, Meinhardt G, Bruix J. Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: the SPACE trial. J Hepatol 2016;64:1090-8.
3. Hoffmann K, Glimm H, Radeleff B, Richter G, Heining C, Schenkel I, Zahlten-Hinguranage A, Schirrmacher P, Schmidt J, Büchler MW, Jaeger D, von Kalle C, Schemmer P. Prospective, randomized, double-blind, multi-center, Phase III clinical study on transarterial chemoembolization (TACE) combined with Sorafenib versus TACE plus placebo in patients with hepatocellular cancer before liver transplantation - HeiLivCa [ISRCTN24081794]. BMC Cancer 2008;8:349.
4. Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology 2014;60:2099-108.
5. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014;74:2913-21.
6. Ryerson AB, Eheman CR, Altekruse SF, Ward JW, Jemal A, Sherman RL, Henley SJ, Holtzman D, Lake A, Noone AM, Anderson RN, Ma J, Ly KN, Cronin KA, Penberthy L, Kohler BA. Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer. Cancer 2016;122:1312-37.
7. Camma C, Cabibbo G, Craxi A. Direct antiviral agents and risk for HCC early recurrence: much ado about nothing. J Hepatol 2016;65:861-2.
8. Umemura A, He F, Taniguchi K, Nakagawa H, Yamachika S, Font-Burgada J, Zhong Z, Subramaniam S, Raghunandan S, Duran A, Linares JF, Reina-Campos M, Umemura S, Valasek MA, Seki E, Yamaguchi K, Koike K, Itoh Y, Diaz-Meco MT, Moscat J, Karin M. p62, upregulated during preneoplasia, induces hepatocellular carcinogenesis by maintaining survival of stressed HCC-initiating cells. Cancer Cell 2016;29:935-48.
9. Ozer Etik D, Suna N, Boyacioglu AS. Management of hepatocellular carcinoma: prevention, surveillance, diagnosis, and staging. Exp Clin Transplant 2017;15:31-5.
10. Oishi N, Yamashita T, Kaneko S. Molecular biology of liver cancer stem cells. Liver Cancer 2014;3:71-84.
11. Xue W, Chen S, Yin H, Tammela T, Papagiannakopoulos T, Joshi NS, Cai W, Yang G, Bronson R, Crowley DG, Zhang F, Anderson DG, Sharp PA, Jacks T. CRISPR-mediated direct mutation of cancer genes in the mouse liver. Nature 2014;514:380-4.
12. Eggert T, Wolter K, Ji J, Ma C, Yevsa T, Klotz S, Medina-Echeverz J, Longerich T, Forgues M, Reisinger F, Heikenwalder M, Wang XW, Zender L, Greten TF. Distinct functions of senescence-associated immune responses in liver tumor surveillance and tumor progression. Cancer Cell 2016;30:533-47.
13. Jang JW, Choi JY, Bae SH, Kim CW, Yoon SK, Cho SH, Yang JM, Ahn BM, Lee CD, Lee YS, Chung KW, Sun HS. Transarterial chemo-lipiodolization can reactivate hepatitis B virus replication in patients with hepatocellular carcinoma. J Hepatol 2004;41:427-35.
14. Yoon SK, Lim NK, Ha SA, Park YG, Choi JY, Chung KW, Sun HS, Choi MJ, Chung J, Wands JR, Kim JW. The human cervical cancer oncogene protein is a biomarker for human hepatocellular carcinoma. Cancer Res 2004;64:5434-41.
15. Zinkin NT, Grall F, Bhaskar K, Otu HH, Spentzos D, Kalmowitz B, Wells M, Guerrero M, Asara JM, Libermann TA, Afdhal NH. Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease. Clin Cancer Res 2008;14:470-7.
16. Ji JF, Shi J, Budhu A, Yu ZP, Forgues M, Roessler S, Ambs S, Chen Y, Meltzer PS, Croce CM, Qin LX, Man K, Lo CM, Lee J, Ng IO, Fan J, Tang ZY, Sun HC, Wang XW. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med 2009;361:1437-47.
17. Jia HL, Ye QH, Qin LX, Budhu A, Forgues M, Chen Y, Liu YK, Sun HC, Wang L, Lu HZ, Shen F, Tang ZY, Wang XW. Gene expression profiling reveals potential biomarkers of human hepatocellular carcinoma. Clin Cancer Res 2007;13:1133-9.
18. Beale G, Chattopadhyay D, Gray J, Stewart S, Hudson M, Day C, Trerotoli P, Giannelli G, Manas D, Reeves H. AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease. BMC Cancer 2008;8:200.
19. Li LM, Hu ZB, Zhou ZX, Chen X, Liu FY, Zhang JF, Shen HB, Zhang CY, Zen K. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. Cancer Res 2010;70:9798-807.
21. Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol 2010;7:448-58.
22. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatology 2010;51:1820-32.
23. Ande SR, Nguyen KH, Gregoire Nyomba BL, Mishra S. Prohibitin-induced, obesity-associated insulin resistance and accompanying low-grade inflammation causes NASH and HCC. Sci Rep 2016;6:23608.
24. Shalapour S, Karin M. Fatty acid-induced T cell loss greases liver carcinogenesis. Cell Metab 2016;23:759-61.
25. Galun E. Liver inflammation and cancer: the role of tissue microenvironment in generating the tumor-promoting niche (TPN) in the development of hepatocellular carcinoma. Hepatology 2016;63:159-68.
26. He G, Karin M. NF-κB and STAT3-key players in liver inflammation and cancer. Cell Res 2011;21:354-6.
27. Qiao L, Li X. Role of chronic inflammation in cancers of the gastrointestinal system and the liver: where we are now. Cancer Lett 2014;345:150-2.
29. Nikolaou K, Sarris M, Talianidis I. Molecular pathways: the complex roles of inflammation pathways in the development and treatment of liver cancer. Clin Cancer Res 2013;19:2810-6.
30. Bartsch H, Nair J. Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: role of lipid peroxidation, DNA damage, and repair. Langenbecks Arch Surg 2006;391:499-510.
31. Kensler TW, Trush MA. Role of oxygen radicals in tumor promotion. Environ Mutagen 1984;6:593-616.
32. Marra M, Sordelli IM, Lombardi A, Lamberti M, Tarantino L, Giudice A, Stiuso P, Abbruzzese A, Sperlongano R, Accardo M, Agresti M, Caraglia M, Sperlongano P. Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview. J Transl Med 2011;9:171.
33. Caldwell SH, Crespo DM, Kang HS, Al-Osaimi AM. Obesity and hepatocellular carcinoma. Gastroenterology 2004;127:S97-103.
34. Matsuzawa-Nagata N, Takamura T, Ando H, Nakamura S, Kurita S, Misu H, Ota T, Yokoyama M, Honda M, Miyamoto K, Kaneko S. Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity. Metabolism 2008;57:1071-7.
35. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 2004;114:1752-61.
36. Steinmetz KA, Potter JD. Vegetables, fruit, and cancer prevention: a review. J Am Diet Assoc 1996;96:1027-39.
37. Block G, Patterson B, Subar A. Fruit, vegetables, and cancer prevention - a review of the epidemiologic evidence. Nutr Cancer 1992;18:1-29.
39. Xu Z, Chen L, Leung L, Yen TS, Lee C, Chan JY. Liver-specific inactivation of the Nrf1 gene in adult mouse leads to nonalcoholic steatohepatitis and hepatic neoplasia. Proc Natl Acad Sci U S A 2005;102:4120-5.
40. Ko C, Siddaiah N, Berger J, Gish R, Brandhagen D, Sterling RK, Cotler SJ, Fontana RJ, McCashland TM, Han SH, Gordon FD, Schilsky ML, Kowdley KV. Prevalence of hepatic iron overload and association with hepatocellular cancer in end-stage liver disease: results from the National Hemochromatosis Transplant Registry. Liver Int 2007;27:1394-401.
41. Marrogi AJ, Khan MA, van Gijssel HE, Welsh JA, Rahim H, Demetris AJ, Kowdley KV, Hussain SP, Nair J, Bartsch H, Okby N, Poirier MC, Ishak KG, Harris CC. Oxidative stress and p53 mutations in the carcinogenesis of iron overload-associated hepatocellular carcinoma. J Natl Cancer Inst 2001;93:1652-5.
42. Houglum K, Filip M, Witztum JL, Chojkier M. Malondialdehyde and 4-hydroxynonenal protein adducts in plasma and liver of rats with iron overload. J Clin Invest 1990;86:1991-8.
43. Hu W, Feng Z, Eveleigh J, Iyer G, Pan J, Amin S, Chung FL, Tang MS. The major lipid peroxidation product, trans-4-hydroxy-2-nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma. Carcinogenesis 2002;23:1781-9.
44. Hussain SP, Raja K, Amstad PA, Sawyer M, Trudel LJ, Wogan GN, Hofseth LJ, Shields PG, Billiar TR, Trautwein C, Hohler T, Galle PR, Phillips DH, Markin R, Marrogi AJ, Harris CC. Increased p53 mutation load in nontumorous human liver of wilson disease and hemochromatosis: oxyradical overload diseases. Proc Natl Acad Sci U S A 2000;97:12770-5.
45. Vautier G, Bomford AB, Portmann BC, Metivier E, Williams R, Ryder SD. p53 mutations in british patients with hepatocellular carcinoma: clustering in genetic hemochromatosis. Gastroenterology 1999;117:154-60.
46. Wang XW, Hussain SP, Huo TI, Wu CG, Forgues M, Hofseth LJ, Brechot C, Harris CC. Molecular pathogenesis of human hepatocellular carcinoma. Toxicology 2002;181-182:43-7.
47. Tanaka S, Mogushi K, Yasen M, Ban D, Noguchi N, Irie T, Kudo A, Nakamura N, Tanaka H, Yamamoto M, Kokudo N, Takayama T, Kawasaki S, Sakamoto M, Arii S. Oxidative stress pathways in noncancerous human liver tissue to predict hepatocellular carcinoma recurrence: a prospective, multicenter study. Hepatology 2011;54:1273-81.
48. Sasaki Y. Does oxidative stress participate in the development of hepatocellular carcinoma? J Gastroenterol 2006;41:1135-48.
49. Paradies G, Paradies V, Ruggiero FM, Petrosillo G. Oxidative stress, cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease. World J Gastroenterol 2014;20:14205-18.
50. Gentric G, Maillet V, Paradis V, Couton D, L'Hermitte A, Panasyuk G, Fromenty B, Celton-Morizur S, Desdouets C. Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease. J Clin Invest 2015;125:981-92.
51. Satapati S, Kucejova B, Duarte JA, Fletcher JA, Reynolds L, Sunny NE, He T, Nair LA, Livingston KA, Fu X, Merritt ME, Sherry AD, Malloy CR, Shelton JM, Lambert J, Parks EJ, Corbin I, Magnuson MA, Browning JD, Burgess SC. Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver. J Clin Invest 2015;125:4447-62.
52. Cichoz-Lach H, Michalak A. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol 2014;20:8082-91.
53. Polimeni L, Del Ben M, Baratta F, Perri L, Albanese F, Pastori D, Violi F, Angelico F. Oxidative stress: new insights on the association of non-alcoholic fatty liver disease and atherosclerosis. World J Hepatol 2015;7:1325-36.
54. Meyskens FL, Buckmeier JA, McNulty SE, Tohidian NB. Activation of nuclear factor-kappa B in human metastatic melanoma cells and the effect of oxidative stress. Clin Cancer Res 1999;5:1197-202.
55. Brown NS, Bicknell R. Hypoxia and oxidative stress in breast cancer. Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res 2001;3:323-7.
56. Toyokuni S, Okamoto K, Yodoi J, Hiai H. Persistent oxidative stress in cancer. FEBS Lett 1995;358:1-3.
57. Suzuki Y, Imai K, Takai K, Hanai T, Hayashi H, Naiki T, Nishigaki Y, Tomita E, Shimizu M, Moriwaki H. Hepatocellular carcinoma patients with increased oxidative stress levels are prone to recurrence after curative treatment: a prospective case series study using the d-ROM test. J Cancer Res Clin Oncol 2013;139:845-52.
58. Jungst C, Cheng B, Gehrke R, Schmitz V, Nischalke HD, Ramakers J, Schramel P, Schirmacher P, Sauerbruch T, Caselmann WH. Oxidative damage is increased in human liver tissue adjacent to hepatocellular carcinoma. Hepatology 2004;39:1663-72.
59. Maki A, Kono H, Gupta M, Asakawa M, Suzuki T, Matsuda M, Fujii H, Rusyn I. Predictive power of biomarkers of oxidative stress and inflammation in patients with hepatitis C virus-associated hepatocellular carcinoma. Ann Surg Oncol 2007;14:1182-90.
60. Bartsch H, Nair J. Oxidative stress and lipid peroxidation-derived DNA-lesions in inflammation driven carcinogenesis. Cancer Detect Prev 2004;28:385-91.
61. Nair U, Bartsch H, Nair J. Lipid peroxidation-induced DNA damage in cancer-prone inflammatory diseases: a review of published adduct types and levels in humans. Free Radic Biol Med 2007;43:1109-20.
62. Fu Y, Nath RG, Dyba M, Cruz IM, Pondicherry SR, Fernandez A, Schultz CL, Yang P, Pan J, Desai D, Krzeminski J, Amin S, Christov PP, Hara Y, Chung FL. In vivo detection of a novel endogenous etheno-DNA adduct derived from arachidonic acid and the effects of antioxidants on its formation. Free Radic Biol Med 2014;73:12-20.
63. Choudhury S, Pan J, Amin S, Chung FL, Roy R. Repair kinetics of trans-4-hydroxynonenal-induced cyclic 1,N(2)-propanodeoxyguanine DNA adducts by human cell nuclear extracts. Biochemistry 2004;43:7514-21.
64. Pan JS, Awoyemi B, Xuan Z, Vohra P, Wang HT, Dyba M, Greenspan E, Fu Y, Creswell K, Zhang L, Berry D, Tang MS, Chung FL. Detection of acrolein-derived cyclic DNA adducts in human cells by monoclonal antibodies. Chem Res Toxicol 2012;25:2788-95.
65. Jia L, Wang XW, Harris CC. Hepatitis B virus X protein inhibits nucleotide excision repair. Int J Cancer 1999;80:875-9.
66. Nath RG, Chung FL. Detection of exocyclic 1,N-2-propanodeoxyguanosine adducts as common DNA lesions in rodents and humans. Proc Natl Acad Sci U S A 1994;91:7491-5.
67. Feng ZH, Hu WW, Hu Y, Tang MS. Acrolein is a major cigarette-related lung cancer agent: preferential binding at p53 mutational hotspots and inhibition of DNA repair. Proc Natl Acad Sci U S A 2006;103:15404-9.
68. Liu XY, Zhu MX, Xie JP. Mutagenicity of acrolein and acrolein-induced DNA adducts. Toxicol Mech Methods 2010;20:36-44.
69. Yang IY, Chan G, Miller H, Huang Y, Torres MC, Johnson F, Moriya M. Mutagenesis by acrolein-derived propanodeoxyguanosine adducts in human cells. Biochemistry 2002;41:13826-32.
70. VanderVeen LA, Hashim MF, Nechev LV, Harris TM, Harris CM, Marnett LJ. Evaluation of the mutagenic potential of the principal DNA adduct of acrolein. J Biol Chem 2001;276:9066-70.
71. Fu Y, Silverstein S, McCutcheon JN, Dyba M, Nath RG, Aggarwal M, Coia H, Bai A, Pan J, Jiang J, Kallakury B, Wang H, Zhang YW, Giaccone G, He AR, Chung FL. An endogenous DNA adduct as a prognostic biomarker for hepatocarcinogenesis and its prevention by Theaphenon E in mice. Hepatology 2018;67:159-70.
72. Yang JD, Malhi H. Green tea consumption: a potential chemopreventive measure for hepatocellular carcinoma? Hepatology 2018;67:10-2.
73. Arbuthnot P, Capovilla A, Kew M. Putative role of hepatitis B virus X protein in hepatocarcinogenesis: effects on apoptosis, DNA repair, mitogen-activated protein kinase and JAK/STAT pathways. J Gastroenterol Hepatol 2000;15:357-68.
74. Kudo M. Adjuvant therapy after curative treatment for hepatocellular carcinoma. Oncology 2011;81:50-5.
75. Schwartz JD, Schwartz M, Mandeli J, Sung M. Neoadjuvant and adjuvant therapy for resectable hepatocellular carcinoma: review of the randomised clinical trials. Lancet Oncol 2002;3:593-603.
76. Poon RT. Prevention of recurrence after resection of hepatocellular carcinoma: a daunting challenge. Hepatology 2011;54:757-9.
77. Izumi N. Prediction and prevention of intrahepatic recurrence of hepatocellular carcinoma. Hepatol Res 2012;42:226-32.
78. Mazzaferro V, Romito R, Schiavo M, Mariani L, Camerini T, Bhoori S, Capussotti L, Calise F, Pellicci R, Belli G, Tagger A, Colombo M, Bonino F, Majno P, Llovet JM, HCC Italian Task Force. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology 2006;44:1543-54.
79. Wang SN, Chuang SC, Lee KT. Efficacy of sorafenib as adjuvant therapy to prevent early recurrence of hepatocellular carcinoma after curative surgery: a pilot study. Hepatol Res 2014;44:523-31.
80. Yoshida H, Shiratori Y, Kudo M, Shiina S, Mizuta T, Kojiro M, Yamamoto K, Koike Y, Saito K, Koyanagi N, Kawabe T, Kawazoe S, Kobashi H, Kasugai H, Osaki Y, Araki Y, Izumi N, Oka H, Tsuji K, Toyota J, Seki T, Osawa T, Masaki N, Ichinose M, Seike M, Ishikawa A, Ueno Y, Tagawa K, Kuromatsu R, Sakisaka S, Ikeda H, Kuroda H, Kokuryu H, Yamashita T, Sakaida I, Katamoto T, Kikuchi K, Nomoto M, Omata M. Effect of vitamin K2 on the recurrence of hepatocellular carcinoma. Hepatology 2011;54:532-40.
81. Yoshiji H, Noguchi R, Toyohara M, Ikenaka Y, Kitade M, Kaji K, Yamazaki M, Yamao J, Mitoro A, Sawai M, Yoshida M, Fujimoto M, Tsujimoto T, Kawaratani H, Uemura M, Fukui H. Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma. J Hepatol 2009;51:315-21.
82. Song CX, Clark TA, Lu XY, Kislyuk A, Dai Q, Turner SW, He C, Korlach J. Sensitive and specific single-molecule sequencing of 5-hydroxymethylcytosine. Nat Methods 2011;9:75-7.
83. Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, Feng Y. The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci 2015;16:26087-124.
84. Ganji SH, Kashyap ML, Kamanna VS. Niacin inhibits fat accumulation, oxidative stress, and inflammatory cytokine IL-8 in cultured hepatocytes: impact on non-alcoholic fatty liver disease. Metabolism 2015;64:982-90.
