REFERENCES
1. Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut 2014;63:844-55.
2. Mardpour S, Hassani SN, Mardpour S, et al. Extracellular vesicles derived from human embryonic stem cell-MSCs ameliorate cirrhosis in thioacetamide-induced chronic liver injury. J Cell Physiol 2018;233:9330-44.
3. McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of hepatocellular carcinoma. Hepatology 2021;73 Suppl 1:4-13.
4. Nahand JS, Jamshidi S, Hamblin MR, et al. Circular RNAs: new epigenetic signatures in viral infections. Front Microbiol 2020;11:1853.
5. Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol 2010;7:448-58.
6. Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020-2.
7. Khadempour-Arani H, Shojaeian A, Mehri-Ghahfarrokhi A, et al. Identifying genotype profile of chronic hepatitis C infection in Southwest Iran. J Res Med Sci 2020;25:85.
8. Gao C, Fang L, Zhao HC, Li JT, Yao SK. Potential role of diabetes mellitus in the progression of cirrhosis to hepatocellular carcinoma: a cross-sectional case-control study from Chinese patients with HBV infection. Hepatobiliary Pancreat Dis Int 2013;12:385-93.
9. Puoti M, Bruno R, Soriano V, et al. Hepatocellular carcinoma in HIV-infected patients: epidemiological features, clinical presentation and outcome. AIDS 2004;18:2285-93.
10. Saito T, Chiba T, Yuki K, et al. Metformin, a diabetes drug, eliminates tumor-initiating hepatocellular carcinoma cells. PLoS One 2013;8:e70010.
11. Choi YK, Park KG. Metabolic roles of AMPK and metformin in cancer cells. Mol Cells 2013;36:279-87.
12. Cunha V, Cotrim HP, Rocha R, Carvalho K, Lins-Kusterer L. Metformin in the prevention of hepatocellular carcinoma in diabetic patients: a systematic review. Ann Hepatol 2020;19:232-7.
13. 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;30:750-8.
14. Saber S, Ghanim AMH, El-Ahwany E, El-Kader EMA. Novel complementary antitumour effects of celastrol and metformin by targeting IκBκB, apoptosis and NLRP3 inflammasome activation in diethylnitrosamine-induced murine hepatocarcinogenesis. Cancer Chemother Pharmacol 2020;85:331-43.
15. Akamatsu N, Cillo U, Cucchetti A, et al. Surgery and hepatocellular carcinoma. Liver Cancer 2016;6:44-50.
16. Idée JM, Guiu B. Use of lipiodol as a drug-delivery system for transcatheter arterial chemoembolization of hepatocellular carcinoma: a review. Crit Rev Oncol Hematol 2013;88:530-49.
17. Li H, Wu F, Duan M, Zhang G. Drug-eluting bead transarterial chemoembolization (TACE) vs conventional TACE in treating hepatocellular carcinoma patients with multiple conventional TACE treatments history: a comparison of efficacy and safety. Medicine 2019;98:e15314.
18. Garrido A, Djouder N. Cirrhosis: a questioned risk factor for hepatocellular carcinoma. Trends Cancer 2021;7:29-36.
19. Lai CL, Yuen MF. Prevention of hepatitis B virus-related hepatocellular carcinoma with antiviral therapy. Hepatology 2013;57:399-408.
20. Chang PY, Chung CH, Chang WC, et al. The effect of propranolol on the prognosis of hepatocellular carcinoma: a nationwide population-based study. PLoS One 2019;14:e0216828.
21. Degasperi E, Anolli MP, Lampertico P. Towards a functional cure for hepatitis B virus: a 2022 update on new antiviral strategies. Viruses 2022;14:2404.
22. Kodali S, Singal AK. Potent suppression of hepatitis B virus and hepatocellular carcinoma: how long is good enough? Hepatobiliary Surg Nutr 2018;7:212-3.
24. Wang G, Chen Z. HBV genomic integration and hepatocellular carcinoma. Adv Gut Microbiome Res 2022;2022:2140886.
25. Nevola R, Beccia D, Rosato V, et al. HBV infection and host interactions: the role in viral persistence and oncogenesis. Int J Mol Sci 2023;24:7651.
26. Wang LH, Baker NE. Correction: salvador-warts-hippo pathway regulates sensory organ development via caspase-dependent nonapoptotic signaling. Cell Death Dis 2019;10:797.
28. Wu Y, Zhang J, Zhang H, Zhai Y. Hepatitis B virus X protein mediates yes-associated protein 1 upregulation in hepatocellular carcinoma. Oncol Lett 2016;12:1971-4.
29. Wang J, Ma L, Weng W, et al. Mutual interaction between YAP and CREB promotes tumorigenesis in liver cancer. Hepatology 2013;58:1011-20.
30. Zhang T, Zhang J, You X, et al. Hepatitis B virus X protein modulates oncogene Yes-associated protein by CREB to promote growth of hepatoma cells. Hepatology 2012;56:2051-9.
31. Oda C, Kamimura K, Shibata O, et al. HBx and YAP expression could promote tumor development and progression in HBV-related hepatocellular carcinoma. Biochem Biophys Rep 2022;32:101352.
32. Li L, Zhao GD, Shi Z, Qi LL, Zhou LY, Fu ZX. The Ras/Raf/MEK/ERK signaling pathway and its role in the occurrence and development of HCC. Oncol Lett 2016;12:3045-50.
33. Younis NS, Ghanim AMH, Saber S. Mebendazole augments sensitivity to sorafenib by targeting MAPK and BCL-2 signalling in n-nitrosodiethylamine-induced murine hepatocellular carcinoma. Sci Rep 2019;9:19095.
34. Marra M, Sordelli IM, Lombardi A, et al. Molecular targets and oxidative stress biomarkers in hepatocellular carcinoma: an overview. J Transl Med 2011;9:171.
35. Méndez-Sánchez N, Vásquez-Fernández F, Zamora-Valdés D, Uribe M. Sorafenib, a systemic therapy for hepatocellular carcinoma. Ann Hepatol 2008;7:46-51.
36. Tu W, Gong J, Tian D, Wang Z. Hepatitis B virus X protein induces SATB1 expression through activation of ERK and p38MAPK pathways to suppress anoikis. Dig Dis Sci 2019;64:3203-14.
37. Shan C, Xu F, Zhang S, et al. Hepatitis B virus X protein promotes liver cell proliferation via a positive cascade loop involving arachidonic acid metabolism and p-ERK1/2. Cell Res 2010;20:563-75.
38. Liao B, Zhou H, Liang H, Li C. Regulation of ERK and AKT pathways by hepatitis B virus X protein via the Notch1 pathway in hepatocellular carcinoma. Int J Oncol 2017;51:1449-59.
39. Orzechowska M, Anusewicz D, Bednarek AK. Functional gene expression differentiation of the notch signaling pathway in female reproductive tract tissues-a comprehensive review with analysis. Front Cell Dev Biol 2020;8:592616.
40. Amata I, Maffei M, Pons M. Phosphorylation of unique domains of Src family kinases. Front Genet 2014;5:181.
41. Belli S, Esposito D, Servetto A, Pesapane A, Formisano L, Bianco R. c-Src and EGFR inhibition in molecular cancer therapy: what else can we improve? Cancers 2020;12:1489.
42. Yang J, Zhang X, Liu L, Yang X, Qian Q, Du B. c-Src promotes the growth and tumorigenesis of hepatocellular carcinoma via the Hippo signaling pathway. Life Sci 2021;264:118711.
43. Yang J, Antin P, Berx G, et al. Guidelines and definitions for research on epithelial-mesenchymal transition. Nat Rev Mol Cell Biol 2020;21:341-52.
44. Yang SZ, Zhang LD, Zhang Y, et al. HBx protein induces EMT through c-Src activation in SMMC-7721 hepatoma cell line. Biochem Biophys Res Commun 2009;382:555-60.
45. Long HZ, Cheng Y, Zhou ZW, Luo HY, Wen DD, Gao LC. PI3K/AKT signal pathway: a target of natural products in the prevention and treatment of alzheimer’s disease and parkinson’s disease. Front Pharmacol 2021;12:648636.
46. Xu W, Yang Z, Lu N. A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition. Cell Adh Migr 2015;9:317-24.
47. Wang Z, Cui X, Hao G, He J. Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma. Open Life Sci 2021;16:1037-44.
48. Wang HY, Yang SL, Liang HF, Li CH. HBx protein promotes oval cell proliferation by up-regulation of cyclin D1 via activation of the MEK/ERK and PI3K/Akt pathways. Int J Mol Sci 2014;15:3507-18.
49. Xiang K, Wang B. Role of the PI3K-AKT-mTOR pathway in hepatitis B virus infection and replication. Mol Med Rep 2018;17:4713-9.
50. Zhu M, Guo J, Li W, et al. HBx induced AFP receptor expressed to activate PI3K/AKT signal to promote expression of Src in liver cells and hepatoma cells. BMC Cancer 2015;15:362.
51. Rawat S, Bouchard MJ. The hepatitis B virus (HBV) HBx protein activates AKT to simultaneously regulate HBV replication and hepatocyte survival. J Virol 2015;89:999-1012.
52. Shokri S, Mahmoudvand S, Taherkhani R, Farshadpour F, Jalalian FA. Complexity on modulation of NF-κB pathways by hepatitis B and C: a double-edged sword in hepatocarcinogenesis. J Cell Physiol 2019;234:14734-42.
53. You H, Qin S, Zhang F, et al. Regulation of pattern-recognition receptor signaling by HBX during hepatitis B virus infection. Front Immunol 2022;13:829923.
54. Budhu A, Wang XW. The role of cytokines in hepatocellular carcinoma. J Leukoc Biol 2006;80:1197-213.
55. Quétier I, Brezillon N, Duriez M, et al. Hepatitis B virus HBx protein impairs liver regeneration through enhanced expression of IL-6 in transgenic mice. J Hepatol 2013;59:285-91.
56. Wang Y, Cui L, Yang G, et al. Hepatitis B e antigen inhibits NF-κB activity by interrupting K63-linked ubiquitination of NEMO. J Virol 2019;93:e00667-18.
57. Cho IR, Oh M, Koh SS, et al. Hepatitis B virus X protein inhibits extracellular IFN-α-mediated signal transduction by downregulation of type I IFN receptor. Int J Mol Med 2012;29:581-6.
58. Yang Y, Zheng B, Han Q, Zhang C, Tian Z, Zhang J. Targeting blockage of STAT3 inhibits hepatitis B virus-related hepatocellular carcinoma. Cancer Biol Ther 2016;17:449-56.
59. Azbazdar Y, Karabicici M, Erdal E, Ozhan G. Regulation of wnt signaling pathways at the plasma membrane and their misregulation in cancer. Front Cell Dev Biol 2021;9:631623.
60. Mahmoudvand S, Shokri S, Taherkhani R, Farshadpour F. Hepatitis C virus core protein modulates several signaling pathways involved in hepatocellular carcinoma. World J Gastroenterol 2019;25:42-58.
61. Nuñez F, Bravo S, Cruzat F, Montecino M, De Ferrari GV. Wnt/β-catenin signaling enhances cyclooxygenase-2 (COX2) transcriptional activity in gastric cancer cells. PLoS One 2011;6:e18562.
62. Zheng BY, Gao WY, Huang XY, et al. HBx promotes the proliferative ability of HL-7702 cells via the COX-2/Wnt/β-catenin pathway. Mol Med Rep 2018;17:8432-8.
63. Srisuttee R, Koh SS, Kim SJ, et al. Hepatitis B virus X (HBX) protein upregulates β-catenin in a human hepatic cell line by sequestering SIRT1 deacetylase. Oncol Rep 2012;28:276-82.
64. Cha MY, Kim CM, Park YM, Ryu WS. Hepatitis B virus X protein is essential for the activation of Wnt/beta-catenin signaling in hepatoma cells. Hepatology 2004;39:1683-93.
65. Prud’homme GJ. Pathobiology of transforming growth factor beta in cancer, fibrosis and immunologic disease, and therapeutic considerations. Lab Invest 2007;87:1077-91.
66. Chen J, Gingold JA, Su X. Immunomodulatory TGF-β signaling in hepatocellular carcinoma. Trends Mol Med 2019;25:1010-23.
67. Liu Y, Xu Y, Ma H, et al. Hepatitis B virus X protein amplifies TGF-β promotion on HCC motility through down-regulating PPM1a. Oncotarget 2016;7:33125-35.
68. Dong KS, Chen Y, Yang G, et al. TGF-β1 accelerates the hepatitis B virus X-induced malignant transformation of hepatic progenitor cells by upregulating miR-199a-3p. Oncogene 2020;39:1807-20.
69. Lim HY, Han J, Yoon H, Jang KL. Tumor suppressor p53 inhibits hepatitis B virus replication by downregulating HBx via E6AP-mediated proteasomal degradation in human hepatocellular carcinoma cell lines. Viruses 2022;14:2313.
70. Yang Y, Qu Y, Li Z, Tan Z, Lei Y, Bai S. Identification of novel characteristics in TP53-mutant hepatocellular carcinoma using bioinformatics. Front Genet 2022;13:874805.
71. Chan C, Thurnherr T, Wang J, et al. Global re-wiring of p53 transcription regulation by the hepatitis B virus X protein. Mol Oncol 2016;10:1183-95.
72. Lacal I, Ventura R. Epigenetic inheritance: concepts, mechanisms and perspectives. Front Mol Neurosci 2018;11:292.
73. Tian Y, Yang W, Song J, Wu Y, Ni B. Hepatitis B virus X protein-induced aberrant epigenetic modifications contributing to human hepatocellular carcinoma pathogenesis. Mol Cell Biol 2013;33:2810-6.
74. Lee SM, Lee YG, Bae JB, et al. HBx induces hypomethylation of distal intragenic CpG islands required for active expression of developmental regulators. Proc Natl Acad Sci USA 2014;111:9555-60.
75. Jiang Y, Han Q, Zhao H, Zhang J. The mechanisms of HBV-induced hepatocellular carcinoma. J Hepatocell Carcinoma 2021;8:435-50.
76. Mahmoudvand S, Shokri S. Effect of lactate on epigenetic regulation in the development of hepatitis B virus-related hepatocellular carcinoma. J Clin Transl Hepatol 2022;10:786-7.
77. Kesheh MM, Mahmoudvand S, Shokri S. Long noncoding RNAs in respiratory viruses: a review. Rev Med Virol 2022;32:e2275.
78. Lin X, Xiang X, Feng B, et al. Targeting long non-coding RNAs in hepatocellular carcinoma: progress and prospects. Front Oncol 2021;11:670838.
79. Hu JJ, Song W, Zhang SD, et al. HBx-upregulated lncRNA UCA1 promotes cell growth and tumorigenesis by recruiting EZH2 and repressing p27Kip1/CDK2 signaling. Sci Rep 2016;6:23521.
80. Salerno D, Chiodo L, Alfano V, et al. Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription. Gut 2020;69:2016-24.
81. Samudh N, Shrilall C, Arbuthnot P, Bloom K, Ely A. Diversity of dysregulated long non-coding RNAs in HBV-related hepatocellular carcinoma. Front Immunol 2022;13:834650.
82. Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther 2016;1:15004.
83. Sartorius K, Swadling L, An P, et al. The multiple roles of hepatitis B virus X protein (HBx) dysregulated MicroRNA in hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and immune pathways. Viruses 2020;12:746.
84. Tian Y, Xiao X, Gong X, et al. HBx promotes cell proliferation by disturbing the cross-talk between miR-181a and PTEN. Sci Rep 2017;7:40089.
85. Zhang Q, Song G, Yao L, et al. miR-3928v is induced by HBx via NF-κB/EGR1 and contributes to hepatocellular carcinoma malignancy by down-regulating VDAC3. J Exp Clin Cancer Res 2018;37:14.
86. Yang S, Yang L, Li X, et al. New insights into autophagy in hepatocellular carcinoma: mechanisms and therapeutic strategies. Am J Cancer Res 2019;9:1329-53.
87. Liu L, Liao JZ, He XX, Li PY. The role of autophagy in hepatocellular carcinoma: friend or foe. Oncotarget 2017;8:57707-22.
88. Cui J, Shen HM, Lim LHK. The role of autophagy in liver cancer: crosstalk in signaling pathways and potential therapeutic targets. Pharmaceuticals 2020;13:432.
89. Wang P, Guo QS, Wang ZW, Qian HX. HBx induces HepG-2 cells autophagy through PI3K/Akt-mTOR pathway. Mol Cell Biochem 2013;372:161-8.
90. Son J, Kim MJ, Lee JS, Kim JY, Chun E, Lee KY. Hepatitis B virus X protein promotes liver cancer progression through autophagy induction in response to TLR4 stimulation. Immune Netw 2021;21:e37.
91. Luo MX, Wong SH, Chan MT, et al. Autophagy mediates HBx-Induced nuclear factor-κB activation and release of IL-6, IL-8, and CXCL2 in hepatocytes. J Cell Physiol 2015;230:2382-9.
92. Jeon JS, Kwon S, Ban K, et al. Regulation of the intracellular ROS level is critical for the antiproliferative effect of quercetin in the hepatocellular carcinoma cell line HepG2. Nutr Cancer 2019;71:861-9.
93. Nour H, Maroua C, Samir D. A study of the relationship between oxidative stress and risk of developing hepatocellular carcinoma in people with hepatitis B infection; A systematic review study. Asian Pac J Cancer Biol 2021;6:316-20.
94. Waris G, Ahsan H. Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog 2006;5:14.
95. Ha HL, Yu DY. HBx-induced reactive oxygen species activates hepatocellular carcinogenesis via dysregulation of PTEN/Akt pathway. World J Gastroenterol 2010;16:4932-7.
96. Lim W, Kwon SH, Cho H, et al. HBx targeting to mitochondria and ROS generation are necessary but insufficient for HBV-induced cyclooxygenase-2 expression. J Mol Med 2010;88:359-69.
97. Suhail M, Sohrab SS, Kamal MA, Azhar EI. Role of hepatitis C virus in hepatocellular carcinoma and neurological disorders: an overview. Front Oncol 2022;12:913231.
98. Aman W, Mousa S, Shiha G, Mousa SA. Current status and future directions in the management of chronic hepatitis C. Virol J 2012;9:57.
99. Sharma SD. Hepatitis C virus: molecular biology & current therapeutic options. Ind J Med Res 2010;131:17-34.
100. Vranjkovic A, Deonarine F, Kaka S, Angel JB, Cooper CL, Crawley AM. Direct-acting antiviral treatment of HCV infection does not resolve the dysfunction of circulating CD8+ T-cells in advanced liver disease. Front Immunol 2019;10:1926.
101. Heredia-Torres TG, Rincón-Sánchez AR, Lozano-Sepúlveda SA, et al. Unraveling the molecular mechanisms involved in HCV-induced carcinogenesis. Viruses 2022;14:2762.
102. Ivanov AV, Bartosch B, Smirnova OA, Isaguliants MG, Kochetkov SN. HCV and oxidative stress in the liver. Viruses 2013;5:439-69.
104. Farinati F, Cardin R, De Maria N, et al. Iron storage, lipid peroxidation and glutathione turnover in chronic anti-HCV positive hepatitis. J Hepatol 1995;22:449-56.
105. Koike K. Hepatitis C virus contributes to hepatocarcinogenesis by modulating metabolic and intracellular signaling pathways. J Gastroenterol Hepatol 2007;22 Suppl 1:S108-11.
106. Ivanov AV, Smirnova OA, Ivanova ON, Masalova OV, Kochetkov SN, Isaguliants MG. Hepatitis C virus proteins activate NRF2/ARE pathway by distinct ROS-dependent and independent mechanisms in HUH7 cells. PLoS One 2011;6:e24957.
107. Ming-Ju H, Yih-Shou H, Tzy-Yen C, Hui-Ling C. Hepatitis C virus E2 protein induce reactive oxygen species (ROS)-related fibrogenesis in the HSC-T6 hepatic stellate cell line. J Cell Biochem 2011;112:233-43.
108. Li S, Ye L, Yu X, et al. Hepatitis C virus NS4B induces unfolded protein response and endoplasmic reticulum overload response-dependent NF-kappaB activation. Virology 2009;391:257-64.
109. Yen HH, Shih KL, Lin TT, Su WW, Soon MS, Liu CS. Decreased mitochondrial deoxyribonucleic acid and increased oxidative damage in chronic hepatitis C. World J Gastroenterol 2012;18:5084-9.
110. Piccoli C, Quarato G, Ripoli M, et al. HCV infection induces mitochondrial bioenergetic unbalance: causes and effects. Biochim Biophys Acta 2009;1787:539-46.
111. Piccoli C, Scrima R, D’Aprile A, et al. Mitochondrial dysfunction in hepatitis C virus infection. Biochim Biophys Acta 2006;1757:1429-37.
112. Qadri I, Iwahashi M, Capasso JM, et al. Induced oxidative stress and activated expression of manganese superoxide dismutase during hepatitis C virus replication: role of JNK, p38 MAPK and AP-1. Biochem J 2004;378:919-28.
113. Nagaraju GP, Dariya B, Kasa P, Peela S, El-Rayes BF. Epigenetics in hepatocellular carcinoma. Semin Cancer Biol 2022;86:622-32.
114. Braghini MR, Lo Re O, Romito I, et al. Epigenetic remodelling in human hepatocellular carcinoma. J Exp Clin Cancer Res 2022;41:107.
115. Man S, Luo C, Yan M, Zhao G, Ma L, Gao W. Treatment for liver cancer: from sorafenib to natural products. Eur J Med Chem 2021;224:113690.
116. Shigekawa Y, Hayami S, Ueno M, et al. Overexpression of KDM5B/JARID1B is associated with poor prognosis in hepatocellular carcinoma. Oncotarget 2018;9:34320-35.
117. Zhou P, Xia J, Zhou YJ, et al. Proportions of acetyl-histone-positive hepatocytes indicate the functional status and prognosis of cirrhotic patients. World J Gastroenterol 2015;21:6665-74.
118. Glozak MA, Seto E. Acetylation/deacetylation modulates the stability of DNA replication licensing factor Cdt1. J Biol Chem 2009;284:11446-53.
119. Plissonnier ML, Herzog K, Levrero M, Zeisel MB. Non-coding RNAs and hepatitis C virus-induced hepatocellular carcinoma. Viruses 2018;10:591.
120. Diaz G, Melis M, Tice A, et al. Identification of microRNAs specifically expressed in hepatitis C virus-associated hepatocellular carcinoma. Int J Cancer 2013;133:816-24.
121. Murakami Y, Yasuda T, Saigo K, et al. Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 2006;25:2537-45.
122. Pezzuto F, Buonaguro L, Buonaguro FM, Tornesello ML. The role of circulating free DNA and MicroRNA in non-invasive diagnosis of HBV- and HCV-Related hepatocellular carcinoma. Int J Mol Sci 2018;19:1007.
123. Tanaka A, Uegaki S, Kurihara H, et al. Hepatic steatosis as a possible risk factor for the development of hepatocellular carcinoma after eradication of hepatitis C virus with antiviral therapy in patients with chronic hepatitis C. World J Gastroenterol 2007;13:5180-7.
124. Ramesh S, Sanyal AJ. Hepatitis C and nonalcoholic fatty liver disease. Semin Liver Dis 2004;24:399-413.
126. Asselah T, Rubbia-Brandt L, Marcellin P, Negro F. Steatosis in chronic hepatitis C: why does it really matter? Gut 2006;55:123-30.
127. Koike K. Steatosis, liver injury, and hepatocarcinogenesis in hepatitis C viral infection. J Gastroenterol 2009;44 Suppl 19:82-8.
128. Saad Y, Shaker O, Nassar Y, Ahmad L, Said M, Esmat G. A polymorphism in the microsomal triglyceride transfer protein can predict the response to antiviral therapy in Egyptian patients with chronic hepatitis C virus genotype 4 infection. Gut Liver 2014;8:655-61.
129. Hino K, Hara Y, Nishina S. Mitochondrial reactive oxygen species as a mystery voice in hepatitis C. Hepatol Res 2014;44:123-32.
130. Bose SK, Shrivastava S, Meyer K, Ray RB, Ray R. Hepatitis C virus activates the mTOR/S6K1 signaling pathway in inhibiting IRS-1 function for insulin resistance. J Virol 2012;86:6315-22.
131. Deng L, Shoji I, Ogawa W, et al. Hepatitis C virus infection promotes hepatic gluconeogenesis through an NS5A-mediated, FoxO1-dependent pathway. J Virol 2011;85:8556-68.
132. Loftus LV, Amend SR, Pienta KJ. Interplay between cell death and cell proliferation reveals new strategies for cancer therapy. Int J Mol Sci 2022;23:4723.
133. Tavakolian S, Goudarzi H, Faghihloo E. Cyclin-dependent kinases and CDK inhibitors in virus-associated cancers. Infect Agent Cancer 2020;15:27.
134. Gutierrez-Chamorro L, Felip E, Ezeonwumelu IJ, Margelí M, Ballana E. Cyclin-dependent kinases as emerging targets for developing novel antiviral therapeutics. Trends Microbiol 2021;29:836-48.
135. Otsuka M, Kato N, Lan K, et al. Hepatitis C virus core protein enhances p53 function through augmentation of DNA binding affinity and transcriptional ability. J Biol Chem 2000;275:34122-30.
136. Wang F, Yoshida I, Takamatsu M, et al. Complex formation between hepatitis C virus core protein and p21Waf1/Cip1/Sdi1. Biochem Biophys Res Commun 2000;273:479-84.
137. Kwun HJ, Jang KL. Dual effects of hepatitis C virus Core protein on the transcription of cyclin-dependent kinase inhibitor p21 gene. J Viral Hepat 2003;10:249-55.
138. Munakata T, Nakamura M, Liang Y, Li K, Lemon SM. Down-regulation of the retinoblastoma tumor suppressor by the hepatitis C virus NS5B RNA-dependent RNA polymerase. Proc Natl Acad Sci USA 2005;102:18159-64.
139. Masalova OV, Lesnova EI, Solyev PN, et al. Modulation of cell death pathways by hepatitis C virus proteins in Huh7.5 hepatoma cells. Int J Mol Sci 2017;18:2346.
140. Qian S, Wei Z, Yang W, Huang J, Yang Y, Wang J. The role of BCL-2 family proteins in regulating apoptosis and cancer therapy. Front Oncol 2022;12:985363.
141. Otsuka M, Kato N, Taniguchi H, et al. Hepatitis C virus core protein inhibits apoptosis via enhanced Bcl-xL expression. Virology 2002;296:84-93.
142. Vescovo T, Refolo G, Vitagliano G, Fimia GM, Piacentini M. Molecular mechanisms of hepatitis C virus-induced hepatocellular carcinoma. Clin Microbiol Infect 2016;22:853-61.
143. Cheng D, Zhang L, Yang G, et al. Hepatitis C virus NS5A drives a PTEN-PI3K/Akt feedback loop to support cell survival. Liver Int 2015;35:1682-91.
144. Easterbrook PJ, Roberts T, Sands A, Peeling R. Diagnosis of viral hepatitis. Curr Opin HIV AIDS 2017;12:302-14.
145. Hong YS, Chang Y, Ryu S, et al. Hepatitis B and C virus infection and diabetes mellitus: a cohort study. Sci Rep 2017;7:4606.
147. Vallianou NG, Evangelopoulos A, Kazazis C. Metformin and cancer. Rev Diabet Stud 2013;10:228-35.
148. Schutte SC, Taylor RN. A tissue-engineered human endometrial stroma that responds to cues for secretory differentiation, decidualization, and menstruation. Fertil Steril 2012;97:997-1003.
149. Miyoshi H, Kato K, Iwama H, et al. Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo. Int J Oncol 2014;45:322-32.
150. Zhang X, Liu P, Shang Y, et al. Metformin and LW6 impairs pancreatic cancer cells and reduces nuclear localization of YAP1. J Cancer 2020;11:479-87.
151. Kamarudin MNA, Sarker MMR, Zhou JR, Parhar I. Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects. J Exp Clin Cancer Res 2019;38:491.
152. Chen J, Chen X. MYBL2 is targeted by miR-143-3p and regulates breast cancer cell proliferation and apoptosis. Oncol Res 2018;26:913-22.
153. Casadei Gardini A, Faloppi L, De Matteis S, et al. Metformin and insulin impact on clinical outcome in patients with advanced hepatocellular carcinoma receiving sorafenib: validation study and biological rationale. Eur J Cancer 2017;86:106-14.
154. Qu Z, Zhang Y, Liao M, Chen Y, Zhao J, Pan Y. In vitro and in vivo antitumoral action of metformin on hepatocellular carcinoma. Hepatol Res 2012;42:922-33.
155. Moon AM, Singal AG, Tapper EB. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin Gastroenterol Hepatol 2020;18:2650-66.
156. Rich NE. Changing epidemiology of hepatocellular carcinoma within the United States and worldwide. Surg Oncol Clin N Am 2024;33:1-12.
157. Garuti F, Neri A, Avanzato F, et al. The changing scenario of hepatocellular carcinoma in Italy: an update. Liver Int 2021;41:585-97.
158. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci 2012;122:253-70.
159. Krishan S, Richardson DR, Sahni S. Adenosine monophosphate-activated kinase and its key role in catabolism: structure, regulation, biological activity, and pharmacological activation. Mol Pharmacol 2015;87:363-77.
160. Oo YH, Sakaguchi S. Regulatory T-cell directed therapies in liver diseases. J Hepatol 2013;59:1127-34.
161. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003;4:330-6.
162. Zheng MH, Gu DN, Braddock M, et al. CD4+ CD25+ regulatory T cells: a therapeutic target for liver diseases. Expert Opin Ther Targets 2008;12:313-26.
163. Li TY, Yang Y, Zhou G, Tu ZK. Immune suppression in chronic hepatitis B infection associated liver disease: a review. World J Gastroenterol 2019;25:3527-37.
164. Sugimoto K, Ikeda F, Stadanlick J, Nunes FA, Alter HJ, Chang KM. Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection. Hepatology 2003;38:1437-48.
165. Granito A, Muratori L, Lalanne C, et al. Hepatocellular carcinoma in viral and autoimmune liver diseases: role of CD4+ CD25+ Foxp3+ regulatory T cells in the immune microenvironment. World J Gastroenterol 2021;27:2994-3009.
166. Takahashi A, Kimura F, Yamanaka A, et al. Metformin impairs growth of endometrial cancer cells via cell cycle arrest and concomitant autophagy and apoptosis. Cancer Cell Int 2014;14:53.
167. Gao C, Fang L, Zhang H, Zhang WS, Li XO, Du SY. Metformin induces autophagy via the AMPK-mTOR signaling pathway in human hepatocellular carcinoma cells. Cancer Manag Res 2020;12:5803-11.
168. Graham GG, Punt J, Arora M, et al. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 2011;50:81-98.
169. Choi J, Roberts LR. Statins and metformin for chemoprevention of hepatocellular carcinoma. Clin Liver Dis 2016;8:48-52.
170. Nkontchou G, Cosson E, Aout M, et al. Impact of metformin on the prognosis of cirrhosis induced by viral hepatitis C in diabetic patients. J Clin Endocrinol Metab 2011;96:2601-8.
171. Del Campo JA, García-Valdecasas M, Gil-Gómez A, et al. Simvastatin and metformin inhibit cell growth in hepatitis C virus infected cells via mTOR increasing PTEN and autophagy. PLoS One 2018;13:e0191805.
172. Xie W, Wang L, Sheng H, et al. Metformin induces growth inhibition and cell cycle arrest by upregulating MicroRNA34a in renal cancer cells. Med Sci Monit 2017;23:29-37.
173. Li JH, Wang Y, Xie XY, et al. Aspirin in combination with TACE in treatment of unresectable HCC: a matched-pairs analysis. Am J Cancer Res 2016;6:2109.
174. Jung WJ, Jang S, Choi WJ, et al. Metformin administration is associated with enhanced response to transarterial chemoembolization for hepatocellular carcinoma in type 2 diabetes patients. Sci Rep 2022;12:14482.
175. Zhou X, Chen J, Yi G, et al. Metformin suppresses hypoxia-induced stabilization of HIF-1α through reprogramming of oxygen metabolism in hepatocellular carcinoma. Oncotarget 2016;7:873-84.
176. Chen ML, Wu CX, Zhang JB, et al. Transarterial chemoembolization combined with metformin improves the prognosis of hepatocellular carcinoma patients with type 2 diabetes. Front Endocrinol 2022;13:996228.
177. Kudo M, Matsui O, Izumi N, et al. Transarterial chemoembolization failure/refractoriness: JSH-LCSGJ criteria 2014 update. Oncology 2014;87 Suppl 1:22-31.
178. Abdelmonsif DA, Sultan AS, El-Hadidy WF, Abdallah DM. Targeting AMPK, mTOR and β-catenin by combined metformin and aspirin therapy in HCC: an appraisal in egyptian HCC patients. Mol Diagn Ther 2018;22:115-27.
179. Ielasi L, Tovoli F, Tonnini M, et al. Beneficial prognostic effects of aspirin in patients receiving sorafenib for hepatocellular carcinoma: a tale of multiple confounders. Cancers 2021;13:6376.
180. Pasche B, Wang M, Pennison M, Jimenez H. Prevention and treatment of cancer with aspirin: where do we stand? Semin Oncol 2014;41:397-401.
181. Kasmari AJ, Welch A, Liu G, Leslie D, McGarrity T, Riley T. Independent of cirrhosis, hepatocellular carcinoma risk is increased with diabetes and metabolic syndrome. Am J Med 2017;130:746.e1-7.
182. Lai SW, Chen PC, Liao KF, Muo CH, Lin CC, Sung FC. Risk of hepatocellular carcinoma in diabetic patients and risk reduction associated with anti-diabetic therapy: a population-based cohort study. Am J Gastroenterol 2012;107:46-52.
183. Chen CI, Kuan CF, Fang YA, et al. Cancer risk in HBV patients with statin and metformin use: a population-based cohort study. Medicine 2015;94:e462.
184. Vilar-Gomez E, Vuppalanchi R, Desai AP, et al. Long-term metformin use may improve clinical outcomes in diabetic patients with non-alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis. Aliment Pharmacol Ther 2019;50:317-28.
185. Tsai PC, Kuo HT, Hung CH, et al. Metformin reduces hepatocellular carcinoma incidence after successful antiviral therapy in patients with diabetes and chronic hepatitis C in Taiwan. J Hepatol 2023;78:281-92.
186. Shen C, Peng C, Shen B, et al. Sirolimus and metformin synergistically inhibit hepatocellular carcinoma cell proliferation and improve long-term survival in patients with HCC related to hepatitis B virus induced cirrhosis after liver transplantation. Oncotarget 2016;7:62647-56.
187. Luo Z, Zang M, Guo W. AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncol 2010;6:457-70.
188. Jiang X, Tan HY, Teng S, Chan YT, Wang D, Wang N. The role of AMP-activated protein kinase as a potential target of treatment of hepatocellular carcinoma. Cancers 2019;11:647.
189. Nakashima K, Takeuchi K, Chihara K, Hotta H, Sada K. Inhibition of hepatitis C virus replication through adenosine monophosphate-activated protein kinase-dependent and -independent pathways. Microbiol Immunol 2011;55:774-82.
190. Foretz M, Hébrard S, Leclerc J, et al. Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest 2010;120:2355-69.
191. Zheng L, Yang W, Wu F, et al. Prognostic significance of AMPK activation and therapeutic effects of metformin in hepatocellular carcinoma. Clin Cancer Res 2013;19:5372-80.
192. Hu JW, Chen B, Zhang J, et al. Novel combination of celecoxib and metformin improves the antitumor effect by inhibiting the growth of hepatocellular carcinoma. J Cancer 2020;11:6437-44.
193. Ling S, Song L, Fan N, et al. Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway. Int J Oncol 2017;50:297-309.
194. Sun R, Zhai R, Ma C, Miao W. Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway. Cancer Med 2020;9:1141-51.
196. Sultuybek G, Soydas T, Yenmis G. NF-κB as the mediator of metformin’s effect on ageing and ageing-related diseases. Clin Exp Pharmacol Physiol 2019;46:413-22.
197. Luedde T, Schwabe RF. NF-κB in the liver-linking injury, fibrosis and hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 2011;8:108-18.
198. He G, Karin M. NF-κB and STAT3 - key players in liver inflammation and cancer. Cell Res 2011;21:159-68.
199. Xu J, Lin H, Wu G, Zhu M, Li M. IL-6/STAT3 is a promising therapeutic target for hepatocellular carcinoma. Front Oncol 2021;11:760971.
202. Wipperman MF, Montrose DC, Gotto AM Jr, Hajjar DP. Mammalian target of rapamycin: a metabolic rheostat for regulating adipose tissue function and cardiovascular health. Am J Pathol 2019;189:492-501.
203. Ferrín G, Guerrero M, Amado V, Rodríguez-Perálvarez M, De la Mata M. Activation of mTOR signaling pathway in hepatocellular carcinoma. Int J Mol Sci 2020;21:1266.
204. Wang Z, Jin W, Jin H, Wang X. mTOR in viral hepatitis and hepatocellular carcinoma: function and treatment. Biomed Res Int 2014;2014:735672.
205. Fischer R, Baumert T, Blum HE. Hepatitis C virus infection and apoptosis. World J Gastroenterol 2007;13:4865-72.
207. Yi Y, Zhang W, Yi J, Xiao ZX. Role of p53 family proteins in metformin anti-cancer activities. J Cancer 2019;10:2434-42.
208. Lu G, Wu Z, Shang J, Xie Z, Chen C, Zhang C. The effects of metformin on autophagy. Biomed Pharmacother 2021;137:111286.
209. Lin D, Reddy V, Osman H, et al. Additional inhibition of Wnt/β-catenin signaling by metformin in DAA Treatments as a novel therapeutic strategy for HCV-infected patients. Cells 2021;10:790.
210. Cai W, Ma Y, Song L, et al. IGF-1R down regulates the sensitivity of hepatocellular carcinoma to sorafenib through the PI3K/akt and RAS/raf/ERK signaling pathways. BMC Cancer 2023;23:87.
211. Vacante F, Senesi P, Montesano A, Paini S, Luzi L, Terruzzi I. Metformin counteracts HCC progression and metastasis enhancing KLF6/p21 expression and downregulating the IGF axis. Int J Endocrinol 2019;2019:7570146.
212. Geh D, Anstee QM, Reeves HL. NAFLD-associated HCC: progress and opportunities. J Hepatocell Carcinoma 2021;8:223-39.
213. Adinolfi LE, Rinaldi L, Guerrera B, et al. NAFLD and NASH in HCV infection: prevalence and significance in hepatic and extrahepatic manifestations. Int J Mol Sci 2016;17:803.
214. Wang B, Li W, Fang H, Zhou H. Hepatitis B virus infection is not associated with fatty liver disease: evidence from a cohort study and functional analysis. Mol Med Rep 2019;19:320-6.
215. Zhang Y, Wang H, Xiao H. Metformin actions on the liver: protection mechanisms emerging in hepatocytes and immune cells against NASH-related HCC. Int J Mol Sci 2021;22:5016.
