Oncogenic Viruses and Hepatocellular Carcinoma

Clinics in Liver Disease

Volumn 19, Issue 2, 2015, Pages 341-360

  Ben Ari, Ziv ^a,b   Weitzman, Ella ^a,b   Safran, Michal ^a  

^a SHEBA MEDICAL CENTER   (Israel)

^b TEL AVIV UNIVERSITY   (Israel)

Author keywords

Hepatitis B; Hepatitis C; Hepatocellular carcinoma; Oncogenic viruses

Indexed keywords

ALPHA INTERFERON; CORE PROTEIN; HEPATITIS B VACCINE; HEPATITIS B VIRUS X PROTEIN; MICRORNA; MONTIRELIN; NONSTRUCTURAL PROTEIN 5A; NONSTRUCTURAL PROTEIN 5B; NUCLEOSIDE DERIVATIVE; NUCLEOTIDE DERIVATIVE; VIRUS DNA; ANTIVIRUS AGENT;

ANTIVIRAL THERAPY; APOPTOSIS; CANCER RISK; CHRONIC HEPATITIS B; CHRONIC HEPATITIS C; DNA REPAIR; EPIGENETICS; GENETIC TRANSCRIPTION; GENOMIC INSTABILITY; HEPATITIS B VIRUS; HEPATITIS C VIRUS; HOST; HUMAN; INFECTION PREVENTION; LIVER CARCINOGENESIS; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FIBROSIS; NONHUMAN; REVIEW; TREATMENT RESPONSE; TUMOR VIRUS; VACCINATION; VIRUS DNA CELL DNA INTERACTION; ANIMAL; CARCINOMA, HEPATOCELLULAR; COMPLICATION; GENETICS; HEPACIVIRUS; HEPATITIS B, CHRONIC; HEPATITIS C, CHRONIC; LIVER NEOPLASMS; PHYSIOLOGY; VIROLOGY;

ANIMALS; ANTIVIRAL AGENTS; CARCINOMA, HEPATOCELLULAR; DNA, VIRAL; HEPACIVIRUS; HEPATITIS B VIRUS; HEPATITIS B, CHRONIC; HEPATITIS C, CHRONIC; HUMANS; LIVER CIRRHOSIS; LIVER NEOPLASMS; ONCOGENIC VIRUSES; VIRUS INTEGRATION;

EID: 84928826002     PISSN: 10893261     EISSN: 15578224     Source Type: Journal    
DOI: 10.1016/j.cld.2015.01.006     Document Type: Review

References (143)

1. El-Serag H.B., Rudolph K.L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 2007, 132:2557-2576.
2. Nguyen V.T., Law M.G., Dore G.J. Hepatitis B-related hepatocellular carcinoma: epidemiological characteristics and disease burden. JViral Hepat 2006, 16:453-463.
3. de Martel C., Ferlay J., Franceschi S., et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 2012, 13(6):607-615.
4. Lemon S.M., McGivern D.R. Is hepatitis C virus carcinogenic?. Gastroenterology 2012, 142:1274-1278.
5. Venook A.P., Papandreou C., Furuse J., et al. The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist 2010, 15:S5-S13.
6. Shlomai A., de Jong Y.P., Rice C.M. Virus associated malignancies: the role of viral hepatitis in hepatocellular carcinoma. Semin Cancer Biol 2014, 26:78-88.
7. Arzumanyan A., Reis H.M., Feitelson M.A. Pathogenic mechanisms in HBV- andHCV-associated hepatocellular carcinoma. Nat Rev Cancer 2013, 13(2):123-135.
8. Papatheodoridis G.V., Lampertico P., Manolakopoulos S., et al. Incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy: a systematic review. JHepatol 2010, 53(2):348-356.
9. Gordon S.C., Lamerato L.E., Rupp L.B., et al. Antiviral therapy for chronic hepatitis B virus infection and development of hepatocellular carcinoma in a US population. Clin Gastroenterol Hepatol 2014, 12(5):885-893.
10. Sherman M. Does hepatitis B treatment reduce the incidence of hepatocellular carcinoma?. Hepatology 2013, 58(1):18-20.
11. Thiele M., Gluud L.L., Krage A. Antiviral therapy in hepatitis B has no effect on mortality and decreases incidence of HCC only in patients with cirrhosis. A meta-analysis of 27 trials and 7,034 patients. Hepatology 2012, 56(S1):642A.
12. Hosaka T., Suzuki F., Kobayashi M., et al. Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection. Hepatology 2013, 58:98-107.
13. Hirakawa M., Ikeda K., Arase Y., et al. Hepatocarcinogenesis following HCV RNA eradication by interferon in chronic hepatitis patients. Intern Med 2008, 47:1637-1643.
14. Yoshida H., Shiratori Y., Moriyama M., et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT study group. Inhibition of Hepatocarcinogenesis by Interferon Therapy. Ann Intern Med 1999, 131:174-181.
15. Yamashita N., Ohho A., Yamasaki A., et al. Hepatocarcinogenesis in chronic hepatitis C patients achieving a sustained virological response to interferon: significance of lifelong periodic cancer screening for improving outcomes. JGastroenterol 2014, 49:1504-1513.
16. Maylin S., Martinot-Peignoux M., Moucari R., et al. Eradication of hepatitis C virus in patients successfully treated for chronic hepatitis C. Gastroenterology 2008, 135:821-829.
17. van der Meer A.J., Veldt B.J., Feld J.J., et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA 2012, 308:2584-2593.
18. Dienstag J.L., Ghany M.G., Morgan T.R., et al. Aprospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C. Hepatology 2011, 54(2):396-405.
19. Gozuacik D., Murakami Y., Saigo K., et al. Identification of human cancer-related genes by naturally occurring hepatitis B virus DNA tagging. Oncogene 2001, 20(43):6233-6240.
20. Murakami Y., Saigo K., Takashima H., et al. Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas. Gut 2005, 54(8):1162-1168.
21. Saigo K., Yoshida K., Ikeda R. Integration of hepatitis B virus DNA into the myeloid/lymphoid or mixed-lineage leukemia (MLL4) gene and rearrangements of MLL4 in human hepatocellular carcinoma. Hum Mutat 2008, 29(5):703-708.
22. Mason W.S., Liu C., Aldrich C.E., et al. Clonal expansion of normal-appearing human hepatocytes during chronic hepatitis B virus infection. JVirol 2010, 84(16):8308-8315.
23. Jiang Z., Jhunjhunwala S., Liu J., et al. The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients. Genome Res 2012, 22(4):593-601.
24. Sung W.K., Zheng H., Li S., et al. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat Genet 2012, 44(7):765-769.
25. Paterlini-Bréchot P., Saigo K., Murakami Y., et al. Hepatitis B virus-related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene. Oncogene 2003, 22(25):3911-3916.
26. Fujimoto A., Totoki Y., Abe T., et al. Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators. Nat Genet 2012, 44(7):760-764.
27. Lau C.C., Sun T., Ching A.K., et al. Viral-human chimeric transcript predisposes risk to liver cancer development and progression. Cancer Cell 2014, 25(3):335-349.
28. Keasler V.V., Hodgson A.J., Madden C.R., et al. Enhancement of hepatitis B virus replication by the regulatory X protein invitro and invivo. JVirol 2007, 81(6):2656-2662.
29. Feitelson M.A., Reis H.M., Tufan N.L., et al. Putative roles of hepatitis B x antigen in the pathogenesis of chronic liver disease. Cancer Lett 2009, 286(1):69-79.
30. Park I.Y., Sohn B.H., Yu E., et al. Aberrant epigenetic modifications in hepatocarcinogenesis induced by hepatitis B virus X protein. Gastroenterology 2007, 132(4):1476-1494.
31. Zhu Y.Z., Zhu R., Fan J., et al. Hepatitis B virus X protein induces hypermethylation of p16(INK4A) promoter via DNA methyltransferases in the early stage of HBV-associated hepatocarcinogenesis. JViral Hepat 2010, 17(2):98-107.
32. Lee J.O., Kwun H.J., Jung J.K., et al. Hepatitis B virus X protein represses E-cadherin expression via activation of DNA methyltransferase 1. Oncogene 2005, 24(44):6617-6625.
33. Jung J.K., Arora P., Pagano J.S., et al. Expression of DNA methyltransferase 1 is activated by hepatitis B virus X protein via a regulatory circuit involving the p16INK4a-cyclin D1-CDK 4/6-pRb-E2F1 pathway. Cancer Res 2007, 67(12):5771-5778.
34. Park S.H., Jung J.K., Lim J.S., et al. Hepatitis B virus X protein overcomes all-trans retinoic acid-induced cellular senescence by downregulating levels of p16 and p21 via DNA methylation. JGen Virol 2011, 92(Pt 6):1309-1317.
35. Liu J., Lian Z., Han S., et al. Downregulation of E-cadherin by hepatitis B virus X antigen in hepatocellular carcinoma. Oncogene 2006, 25(7):1008-1017.
36. Osada T., Sakamoto M., Ino Y., et al. E-cadherin is involved in the intrahepatic metastasis of hepatocellular carcinoma. Hepatology 1996, 24(6):1460-1467.
37. Xie Q., Chen L., Shan X., et al. Epigenetic silencing of SFRP1 and SFRP5 by hepatitis B virus X protein enhances hepatoma cell tumorigenicity through Wnt signaling pathway. Int J Cancer 2014, 135(3):635-646.
38. Zhao J., Wu G., Bu F., et al. Epigenetic silence of ankyrin-repeat-containing, SH3-domain-containing, and proline-rich-region- containing protein 1 (ASPP1) and ASPP2 genes promotes tumor growth in hepatitis B virus-positive hepatocellular carcinoma. Hepatology 2010, 51(1):142-153.
39. Zheng D.L., Zhang L., Cheng N., et al. Epigenetic modification induced by hepatitis B virus X protein via interaction with de novo DNA methyltransferase DNMT3A. JHepatol 2009, 50(2):377-387.
40. Tong A., Gou L., Lau Q.C., et al. Proteomic profiling identifies aberrant epigenetic modifications induced by hepatitis B virus X protein. JProteome Res 2009, 8(2):1037-1046.
41. Tang S.H., Hu W., Hu J.J., et al. Hepatitis B virus X protein promotes P3 transcript expression of the insulin-like growth factor 2 (IGF2) gene via inducing hypomethylation of P3 promoter in hepatocellular carcinoma. Liver Int 2015, 35:608-619.
42. Lee S.M., Lee Y.G., Bae J.B., et al. HBx induces hypomethylation of distal intragenic CpG islands required for active expression of developmental regulators. Proc Natl Acad Sci USA 2014, 111(26):9555-9560.
43. Bannister A.J., Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature 1996, 384(6610):641-643.
44. Ogryzko V.V., Schiltz R.L., Russanova V., et al. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 1996, 87(5):953-959.
45. Cougot D., Wu Y., Cairo S., et al. The hepatitis B virus X protein functionally interacts with CREB-binding protein/p300 in the regulation of CREB-mediated transcription. JBiol Chem 2007, 282(7):4277-4287.
46. Shon J.K., Shon B.H., Park I.Y., et al. Hepatitis B virus-X protein recruits histone deacetylase 1 to repress insulin-like growth factor binding protein 3 transcription. Virus Res 2009, 139(1):14-21.
47. Arzumanyan A., Friedman T., Kotei E., et al. Epigenetic repression of E-cadherin expression by hepatitis B virus x antigen in liver cancer. Oncogene 2012, 31(5):563-572.
48. Wang Y., Lu Y., Toh S.T., et al. Lethal-7 is down-regulated by the hepatitis B virus x protein and targets signal transducer and activator of transcription 3. JHepatol 2010, 53(1):57-66.
49. Zhao J., Wang W., Huang Y., et al. HBx Elevates oncoprotein AEG-1 expression to promote cell migration by downregulating miR-375 and miR-136 in malignant hepatocytes. DNA Cell Biol 2014, 33:715-722.
50. Zhang T., Zhang J., Cui M., et al. Hepatitis B virus X protein inhibits tumor suppressor miR-205 through inducing hypermethylation of miR-205 promoter to enhance carcinogenesis. Neoplasia 2013, 15(11):1282-1291.
51. Liu F., You X., Chi X., et al. Hepatitis B virus X protein mutant HBxδ127 promotes proliferation of hepatoma cells through up-regulating miR-215 targeting PTPRT. Biochem Biophys Res Commun 2014, 444(2):128-134.
52. Yip W.K., Cheng A.S., Zhu R., et al. Carboxyl-terminal truncated HBx regulates a distinct microRNA transcription program in hepatocellular carcinoma development. PLoS One 2011, 6(8):e22888.
53. Kew M.C. Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma. JGastroenterol Hepatol 2011, 26(Suppl 1):144-152.
54. Ye L., Dong N., Wang Q., et al. Progressive changes in hepatoma cells stably transfected with hepatitis B virus X gene. Intervirology 2008, 51(1):50-58.
55. Knoll S., Fürst K., Thomas S., et al. Dissection of cell context-dependent interactions between HBx and p53 family members in regulation of apoptosis: a role for HBV-induced HCC. Cell Cycle 2011, 10(20):3554-3565.
56. Chen H.Y., Tang N.H., Lin N., et al. Hepatitis B virus X protein induces apoptosis and cell cycle deregulation through interfering with DNA repair and checkpoint responses. Hepatol Res 2008, 38(2):174-182.
57. van Breugel P.C., Robert E.I., Mueller H., et al. Hepatitis B virus X protein stimulates gene expression selectively from extrachromosomal DNA templates. Hepatology 2012, 56(6):2116-2124.
58. Guo L., Wang X., Ren L., et al. HBx affects CUL4-DDB1 function in both positive and negative manners. Biochem Biophys Res Commun 2014, 450(4):1492-1497.
59. Martin-Lluesma S., Schaeffer C., Robert E.I., et al. Hepatitis B virus X protein affects S phase progression leading to chromosome segregation defects by binding to damaged DNA binding protein 1. Hepatology 2008, 48(5):1467-1476.
60. Moriya K., Fujie H., Shintani Y., et al. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med 1998, 4(9):1065-1067.
61. Tanaka N., Moriya K., Kiyosawa K., et al. Hepatitis C virus core protein induces spontaneous and persistent activation of peroxisome proliferator-activated receptor alpha in transgenic mice: implications for HCV-associated hepatocarcinogenesis. Int J Cancer 2008, 122(1):124-131.
62. Basu A., Meyer K., Lai K.K., et al. Microarray analyses and molecular profiling of Stat3 signaling pathway induced by hepatitis C virus core protein in human hepatocytes. Virology 2006, 349(2):347-358.
63. Pez F., Lopez A., Kim M., et al. Wnt signaling and hepatocarcinogenesis: molecular targets for the development of innovative anticancer drugs. JHepatol 2013, 59(5):1107-1117.
64. Fukutomi T., Zhou Y., Kawai S., et al. Hepatitis C virus core protein stimulates hepatocyte growth: correlation with upregulation of wnt-1 expression. Hepatology 2005, 41(5):1096-1105.
65. Huang S., Xie Y., Yang P., et al. HCV core protein-induced down-regulation of microRNA-152 promoted aberrant proliferation by regulating Wnt1 in HepG2 cells. PLoS One 2014, 9(1):e81730.
66. Quan H., Zhou F., Nie D., et al. Hepatitis C virus core protein epigenetically silences SFRP1 and enhances HCC aggressiveness by inducing epithelial-mesenchymal transition. Oncogene 2014, 33(22):2826-2835.
67. Benzoubir N., Lejamtel C., Battaglia S., et al. HCV core-mediated activation of latent TGF-β via thrombospondin drives the crosstalk between hepatocytes and stromal environment. JHepatol 2013, 59(6):1160-1168.
68. Zhu C., Liu X., Wang S., et al. Hepatitis C virus core protein induces hypoxia-inducible factor 1α-mediated vascular endothelial growth factor expression in Huh7.5.1 cells. Mol Med Rep 2014, 9(5):2010-2014.
69. Sakamuro D., Furukawa T., Takegami T. Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells. JVirol 1995, 69(6):3893-3896.
70. Zemel R., Gerechet S., Greif H., et al. Cell transformation induced by hepatitis C virus NS3 serine protease. JViral Hepat 2001, 8(2):96-102.
71. Zemel R., Kazatsker A., Greif F., et al. Mutations at vicinity of catalytic sites of hepatitis C virus NS3 serine protease gene isolated from hepatocellular carcinoma tissue. Dig Dis Sci 2000, 45(11):2199-2202.
72. Kwun H.J., Jung E.Y., Ahn J.Y., et al. p53-dependent transcriptional repression of p21(waf1) by hepatitis C virus NS3. JGen Virol 2001, 82(Pt 9):2235-2241.
73. Feng D.Y., Sun Y., Cheng R.X., et al. Effect of hepatitis C virus nonstructural protein NS3 on proliferation and MAPK phosphorylation of normal hepatocyte line. World J Gastroenterol 2005, 11(14):2157-2161.
74. Li B., Li X., Li Y., et al. The effects of hepatitis C virus non-structural protein 3 on cell growth mediated by extracellular signal-related kinase cascades in human hepatocytes invitro. Int J Mol Med 2010, 26(2):273-279.
75. Cheng P.L., Chang M.H., Chao C.H., et al. Hepatitis C viral proteins interact with Smad3 and differentially regulate TGF-beta/Smad3-mediated transcriptional activation. Oncogene 2004, 23(47):7821-7838.
76. Verga-Gérard A., Porcherot M., Meyniel-Schicklin L., et al. Hepatitis C virus/human interactome identifies SMURF2 and the viral protease as critical elements for the control of TGF-β signaling. FASEB J 2013, 27(10):4027-4040.
77. Sakata K., Hara M., Terada T., et al. HCV NS3 protease enhances liver fibrosis via binding to and activating TGF-β type I receptor. Sci Rep 2013, 3:3243.
78. Ghosh A.K., Steele R., Meyer K., et al. Hepatitis C virus NS5A protein modulates cell cycle regulatory genes and promotes cell growth. JGen Virol 1999, 80(Pt 5):1179-1183.
79. Majumder M., Ghosh A.K., Steele R., et al. Hepatitis C virus NS5A physically associates with p53 and regulates p21/waf1 gene expression in a p53-dependent manner. JVirol 2001, 75(3):1401-1407.
80. Lan K.H., Sheu M.L., Hwang S.J., et al. HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis. Oncogene 2002, 21(31):4801-4811.
81. Cheng D., Zhao L., Zhang L., et al. p53 controls hepatitis C virus non-structural protein 5A-mediated downregulation of GADD45α expression via the NF-κB and PI3K-Akt pathways. JGen Virol 2013, 94(Pt 2):326-335.
82. Tamura R.E., de Vasconcellos J.F., Sarkar D., et al. GADD45 proteins: central players in tumorigenesis. Curr Mol Med 2012, 12(5):634-651.
83. He Y., Nakao H., Tan S.L., et al. Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase. JVirol 2002, 76(18):9207-9217.
84. Street A., Macdonald A., McCormick C., et al. Hepatitis C virus NS5A-mediated activation of phosphoinositide 3-kinase results in stabilization of cellular beta-catenin and stimulation of beta-catenin-responsive transcription. JVirol 2005, 79(8):5006-5016.
85. Milward A., Mankouri J., Harris M. Hepatitis C virus NS5A protein interacts with beta-catenin and stimulates its transcriptional activity in a phosphoinositide-3 kinase-dependent fashion. JGen Virol 2010, 91(Pt 2):3.
86. Higgs M.R., Lerat H., Pawlotsky J.M. Hepatitis C virus-induced activation of β-catenin promotes c-Myc expression and a cascade of pro-carcinogenetic events. Oncogene 2013, 32(39):4683-4693.
87. McGivern D.R., Lemon S.M. Virus-specific mechanisms of carcinogenesis in hepatitis C virus associated liver cancer. Oncogene 2011, 30(17):1969-1983.
88. Munakata T., Liang Y., Kim S., et al. Hepatitis C virus induces E6AP-dependent degradation of the retinoblastoma protein. PLoS Pathog 2007, 3(9):1335-1347.
89. Jopling C.L., Yi M., Lancaster A.M., et al. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 2005, 309(5740):1577-1581.
90. Bai S., Nasser M.W., Wang B., et al. MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. JBiol Chem 2009, 284(46):32015-32027.
91. Llovet J.M., Burroughs A., Bruix J. Hepatocellular carcinoma. Lancet 2003, 362:1907-1917.
92. Fattovich G., Stroffolini T., Zagni I., et al. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004, 127:S35-S50.
93. Simonetti R.G., Camma C., Fiorello F., et al. Hepatocellular carcinoma. A worldwide problem and the major risk factors. Dig Dis Sci 1991, 36:962-972.
94. Chen J.D., Yang H.I., Iloeje U.H., et al. Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death. Gastroenterology 2010, 138(5):1747-1754.
95. Chen C.J., Yang H.I., Su J., et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006, 295(1):65-73.
96. Liu C.J., Chen B.F., Chen P.J., et al. Role of hepatitis B virus precore/core promoter mutations and serum viral load on noncirrhotic hepatocellular carcinoma: a case-control study. JInfect Dis 2006, 194:594-599.
97. Chemin I., Trépo C. Clinical impact of occult HBV infections. JClin Virol 2005, 34(Suppl 1):S15-S21.
98. De Mitri M.S., Cassini R., Bernardi M. Hepatitis B virus-related hepatocarcinogenesis: molecular oncogenic potential of clear or occult infections. Eur J Cancer 2010, 46(12):2178-2186.
99. Huang X., Hollinger F.B. Occult hepatitis B virus infection and hepatocellular carcinoma: a systematic review. JViral Hepat 2014, 21(3):153-162.
100. Buendia M.A. Hepatitis B viruses and hepatocellular carcinoma. Adv Cancer Res 1992, 59:167-226.
101. Wong N., Lai P., Lee S.W., et al. Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis: relationship to disease stage, tumor size, and cirrhosis. Am J Pathol 1999, 154:37-43.
102. Fu X., Wan S., Hann H.W., et al. Relative telomere length: a novel non-invasive biomarker for the risk of non-cirrhotic hepatocellular carcinoma in patients with chronic hepatitis B infection. Eur J Cancer 2012, 48(7):1014-1022.
103. Zhang X., Dong N., Zhang H., et al. Effects of hepatitis B virus X protein on human telomerase reverse transcriptase expression and activity in hepatoma cells. JLab Clin Med 2005, 145:98-104.
104. el-Refaie A., Savage K., Bhattacharya S., et al. HCV-associated hepatocellular carcinoma without cirrhosis. JHepatol 1996, 24(3):277-285.
105. Yeh M.M., Daniel H.D., Torbenson M. Hepatitis C-associated hepatocellular carcinomas in non-cirrhotic livers. Mod Pathol 2010, 23(2):276-283.
106. De Mitri M.S., Poussin K., Baccarini P. HCV-associated liver cancer without cirrhosis. Lancet 1995, 345(8947):413-415.
107. Lok A.S., Seeff L.B., Morgan T.R., et al. Incidence of hepatocellular carcinoma and associated risk factors in hepatitis C-related advanced liver disease. Gastroenterology 2009, 136:138-148.
108. Herr W., Gerken G., Poralla T., et al. Hepatitis C virus associated primary hepatocellular carcinoma in a noncirrhotic liver. Clin Investig 1993, 71:49-53.
109. Nash K.L., Woodall T., Brown A.S., et al. Hepatocellular carcinoma in patients with chronic hepatitis C virus infection without cirrhosis. World J Gastroenterol 2010, 16:4061-4065.
110. Albeldawi M., Soliman M., Lopez R., et al. Hepatitis C virus-associated primary hepatocellular carcinoma in non-cirrhotic patients. Dig Dis Sci 2012, 57(12):3265-3270.
111. Lee M.H., Yang H.I., Lu S.N., et al. Hepatitis C virus seromarkers and subsequent risk of hepatocellular carcinoma: long-term predictors from a community-based cohort study. JClin Oncol 2010, 28(30):4587-4593.
112. Lavanchy D. Viral hepatitis: global goals for vaccination. JClin Virol 2012, 55:296-302.
113. Chang M.H., You S.L., Chen C.J., et al. Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study. JNatl Cancer Inst 2009, 101:1348-1355.
114. Chiang C.J., Yang Y.W., You S.L., et al. Thirty-year outcomes of the national hepatitis B immunization program in Taiwan. JAMA 2013, 310(9):974-976.
115. Wichajarn K., Kosalaraksa P., Wiangnon S. Incidence of hepatocellular carcinoma in children in Khon Kaen before and after national hepatitis B vaccine program. Asian Pac J Cancer Prev 2008, 9:507-509.
116. Lanier A.P., Holck P., Ehrsam Day G., et al. Childhood cancer among Alaska natives. Pediatrics 2003, 112:e396.
117. Lai C.L., Yuen M.F. Prevention of hepatitis B virus-related hepatocellular carcinoma with antiviral therapy. Hepatology 2013, 57(1):399-408.
118. Iavarone M., Colombo M. HBV infection and hepatocellular carcinoma. Clin Liver Dis 2013, 17(3):375-397.
119. Miyake Y., Kobashi H., Yamamoto K. Meta-analysis: the effect of interferon on development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. JGastroenterol 2009, 44(5):470-475.
120. Yang Y.F., Zhao W., Zhong Y.D., et al. Interferon therapy in chronic hepatitis B reduces progression to cirrhosis and hepatocellular carcinoma: a meta-analysis. JViral Hepat 2009, 16(4):265-271.
121. Sung J.J., Tsoi K.K., Wong V.W., et al. Meta-analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. Aliment Pharmacol Ther 2008, 28(9):1067-1077.
122. Shen Y.C., Hsu C., Cheng C.C., et al. Acritical evaluation of the preventive effect of antiviral therapy on the development of hepatocellular carcinoma in patients with chronic hepatitis C or B: a novel approach by using meta-regression. Oncology 2012, 82(5):275-289.
123. Cammà C., Giunta M., Andreone P., et al. Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach. JHepatol 2001, 34(4):593-602.
124. Zhang C.H., Xu G.L., Jia W.D., et al. Effects of interferon treatment on development and progression of hepatocellular carcinoma in patients with chronic virus infection: a meta-analysis of randomized controlled trials. Int J Cancer 2011, 129(5):1254-1264.
125. Jin H., Pan N., Mou Y., et al. Long-term effect of interferon treatment on the progression of chronic hepatitis B: Bayesian meta-analysis and meta-regression. Hepatol Res 2011, 41(6):512-523.
126. Papatheodoridis G.V., Manolakopoulos S., Touloumi G., et al. Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s) starting with lamivudine monotherapy: results of the nationwide HEPNET Greece cohort study. Gut 2011, 60:1109-1116.
127. Papatheodoridis G.V., Manolakopoulos S., Touloumi G., et al. Hepatocellular carcinoma risk in HBeAg-negative chronic hepatitis B patients with or without cirrhosis treated with entecavir: HepNet. Greece cohort. JViral Hepat 2015, 22:118-125.
128. Lampertico P., Soffredini R., Vigano M., et al. Entecavir treatment for NUC naive, field practice patients with chronic hepatitis B: excellent viral suppression and safety profile over 5 years of treatment. Hepatology 2012, 56(S1):370A.
129. Kim W.R., Berg T., Loomba R., et al. Long term tenofovir disoproxil fumarate (TDF) therapy and the risk of hepatocellular carcinoma. JHepatol 2013, 58:S19.
130. Yu M.L., Lin S.M., Chuang W.L., et al. Asustained virological response to interferon or interferon/ribavirin reduces hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide, multicenter study in Taiwan. Antivir Ther 2006, 11:985-994.
131. 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(39):5180-5187.
132. Cardoso A.C., Moucari R., Figueiredo-Mendes C., et al. Impact of peginterferon and ribavirin therapy on hepatocellular carcinoma: incidence and survival in hepatitis C patients with advanced fibrosis. JHepatol 2010, 52(5):652-657.
133. Ogawa E., Furusyo N., Kajiwara E., et al. Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma in patients with chronic hepatitis C: a prospective, multicenter study. JHepatol 2013, 58(3):495-501.
134. Morgan R.L., Baack B., Smith B.D., et al. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med 2013, 158(5 Pt 1):329-337.
135. Toyoda H., Kumada T., Nakano S., et al. Effect of the dose and duration of interferon-therapy on the incidence of hepatocellular carcinoma in noncirrhotic patients with a nonsustained response to interferon for chronic hepatitis C. Oncology 2001, 61:134-142.
136. Ikeda K., Saitoh S., Kobayashi M., et al. Long-term interferon therapy for 1 year or longer reduces the hepatocellular carcinogenesis rate in patients with liver cirrhosis caused by hepatitis C virus: a pilot study. JGastroenterol Hepatol 2001, 16:406-415.
137. Lok A.S., Everhart J.E., Wright E.C., et al. Maintenance peginterferon therapy and other factors associated with hepatocellular carcinoma in patients with advanced hepatitis C. Gastroenterology 2011, 140:840-849.
138. Bruix J., Poynard T., Colombo M., et al. Maintenance therapy with peginterferon alfa-2b does not prevent hepatocellular carcinoma in cirrhotic patients with chronic hepatitis C. Gastroenterology 2011, 140(7):1990-1999.
139. Huang C.F., Yeh M.L., Tsai P.C., et al. Baseline gamma-glutamyl transferase levels strongly correlate with hepatocellular carcinoma development in non-cirrhotic patients with successful hepatitis C virus eradication. JHepatol 2014, 61(1):67-74.
140. Scherzer T.M., Reddy K.R., Wrba F., et al. Hepatocellular carcinoma in long-term sustained virological responders following antiviral combination therapy for chronic hepatitis C. JViral Hepat 2008, 15(9):659-665.
141. Nagaoki Y., Aikata H., Miyaki D., et al. Clinical features and prognosis in patients with hepatocellular carcinoma that developed after hepatitis C virus eradication with interferon therapy. JGastroenterol 2011, 46(6):799-808.
142. Aleman S., Rahbin N., Weiland O., et al. Arisk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis. Clin Infect Dis 2013, 57(2):230-236.
143. Bruix J., Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011, 53:1020-1022.