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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 7
Jul.  2017
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Pathogenesis of hepatocellular carcinoma induced by HBV and HCV infection

DOI: 10.3969/j.issn.1001-5256.2017.07.040
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  • Received Date: 2017-01-20
  • Published Date: 2017-07-20
  • Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide.Surgery is the preferred therapy for patients with small HCC;however, there still lack effective therapies for advanced HCC and postoperative recurrence and metastasis, leading to its high mortality.Persistent hepatitis virus infection, mainly hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, is the most important cause of HCC.Through various signal transduction mechanisms, hepatitis virus changes gene expression in hepatocytes, blocks or alters immune response, regulates the microenvironment in the liver, and thus promotes the development and progression of HCC.This article reviews the pathogenesis of HCC induced by HBV and HCV infection, in order to provide new approaches for the prevention and treatment of HCC.

     

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  • [1]FERLAY J, SOERJOMATARAM I, DIKSHIT R, et al.Cancer incidence and mortality worldwide:sources, methods and major patterns in GLOBOCAN 2012[J].Int J Cancer, 2015, 136 (5) :e359-e386.
    [2]SHEN F, CHENG ZJ.Understanding of clinical research on liver cancer in the era of precision medicine and big data[J].Chin J Pract Surg, 2016, 36 (6) :599-602. (in Chinese) 沈锋, 程张军.精准医学和大数据时代对肝癌临床研究的认识[J].中国实用外科杂志, 2016, 36 (6) :599-602.
    [3]WU WB, YI HF, HUANG WQ, et al.Study on the relationship between hepatitis B virus infection and recurrence and metastasis of hepatocellular carcinoma[J].Chin J Nosocomiol, 2016, 26 (4) :744-746. (in Chinese) 吴卫兵, 尹华发, 黄文琪, 等.肝炎病毒感染与肝细胞性肝癌患者术后复发转移的相关性研究[J].中华医院感染学杂志, 2016, 26 (4) :744-746.
    [4]SUN Q, WANG R, WANG Y, et al.Notch1 is a potential therapeutic target for the treatment of human hepatitis B virus X protein-associated hepatocellular carcinoma[J].Oncol Rep, 2014, 31 (2) :933-939.
    [5]LU Y, LI W, ZHU MY, et al.The effect of hepatitis B virus Xgene on the expression of ras in human hepatoma cells Bel7402[J].China Med Herald, 2015, 12 (32) :9-12. (in chinese) 鲁琰, 李伟, 朱明月, 等.乙肝病毒X基因对肝癌Bel7402细胞ras基因表达的影响[J].中国医药导报, 2015, 12 (32) :9-12.
    [6]LI D, DING J, CHEN Z, et al.Accurately mapping the location of the binding site for the interaction between hepatitis B virus X protein and cytochrome c oxidase III[J].Mol Med, 2015, 35 (2) :319-324.
    [7]WANG MR.Interpretation of the guidelines for prevention and treatment of chronic hepatitis B in the 2008 Asia Pacific Society for the study of liver diseases[J].Mil Med J Southeast China, 2008, 10 (4) :241-242. (in Chinese) 汪茂荣.解读《2008亚太肝病研究学会慢性乙型肝炎防治指南》[J].东南国防医药, 2008, 10 (4) :241-242.
    [8]DATTA S, ROYCHOUDHURY S, GHOSH A, et al.Distinct distribution pattern of hepatitis B virus genotype C and D in liver tissue and serum of dual genotype infected liver cirrhosis and hepatocellular carcinoma patients[J].PLo S One, 2014, 9 (7) :e102573.
    [9]DATTA S, GHOSH A, DASGUPTA D, et al.Novel point and combo-mutations in the genome of hepatitis B virus-genotype D:characterization and impact on liver disease progression to hepatocellular carcinoma[J].PLo S One, 2014, 9 (10) :e110012.
    [10]CHEN KH, GAO T, PAN JF, et al.DHA can inhibit the migration and invasion of hepatocellular carcinoma cells induced by aflatoxin B1[J].J South Med Univ, 2016, 36 (7) :952-956. (in Chinese) 陈可和, 高婷, 潘金飞, 等.DHA可抑制黄曲霉素B1诱导的肝癌细胞迁移及侵袭[J].南方医科大学学报, 2016, 36 (7) :952-956.
    [11]WU HC, TSAI HW, TENG CF, et al.Ground-glass hepatocytes co-expressing hepatitis B virus X protein and surface antigens exhibitenhanced oncogenic effects and tumorigenesis[J].Hum Pathol, 2014, 45 (6) :1294-1301.
    [12]PARK CY, CHOI SH, KANG SM, et al.Nonstructural 5A protein activates beta-catenin signaling cascades:implication of hepatitis C virus-induced liver pathogenesis[J].J Hepatol, 2009, 51 (5) :853-864.
    [13]KASPRZAK A, ADAMEK A.Role of hepatitis C virus proteins (C, NS3, NS5A) in hepatic oncogenesis[J].Hepatol Res, 2008, 38 (1) :1-26.
    [14]PANG T, XING HC.Analysis of the relationship between drug resistance gene mutation and hepatocellular carcinoma in HBV infected patients[J].J Clin Hepatol, 2017, 33 (1) :82-86. (in Chinese) 庞婷, 邢卉春.HBV感染者耐药基因突变与肝细胞癌的相关性分析[J].临床肝胆病杂志, 2017, 33 (1) :82-86.
    [15]SHU Y, WANG W, DAI P, et al.Mutation analysis of hepatitis B virus genome BCP/Pre C gene mutation in patients with hepatocellular carcinoma[J].Chin J Virol, 2017, 33 (1) :36-43. (in Chinese) 束毅, 王伟, 代鹏, 等.肝癌患者体内乙型肝炎病毒基因组BCP/Pre C区基因突变多样性分析[J].病毒学报, 2017, 33 (1) :36-43.
    [16]HUANG Y, LUO X, CHEN YM, et al.Study on the expression of HBV covalently closed circular DNA in liver tissue of patients with hepatocellular carcinoma and its correlation with e antigen[J].JChongqing Med Univ, 2015, 40 (11) :1430-1433. (in Chinese) 黄瑶, 罗璇, 陈彦猛, 等.肝癌患者肝组织中乙肝病毒共价闭合环状DNA表达水平及与e抗原相关性研究[J].重庆医科大学学报, 2015, 40 (11) :1430-1433.
    [17]PARK YM, JANG JM, YOO SH, et al.Combinations of eight key mutations in the X/pre C region and genomic activity of hepatitis Bvirus are associated with hepatocellular carcinoma[J].J Viral Hepat, 2014, 21 (3) :171-177.
    [18]SAMUELE de MINICIS, MARCO MARZIONI, ANTONIO BENE-DETTI, et al.New insights into hepatocellular carcinoma:from experiment to clinic[J].Chin J Gen Surg, 2015, 24 (1) :1-9. (in Chinese) Samuele de Minicis, Marco Marzioni, Antonio Benedetti, 等.肝细胞癌的新见解:从实验到临床[J].中国普通外科杂志, 2015, 24 (1) :1-9.
    [19]PEZ F, LOPEZ A, KIM M, et al.Wnt signaling and hepatocarcinogenesis:molecular targets for the development of innovative anticancer drugs[J].J Hepatol, 2013, 59 (5) :1107-1117.
    [20]LUCIFORA J, XIA Y, REISINGER F, et al.Specific and nonhepatotoxic degradation of nuclear hepatitis B virus ccc DNA[J].Science, 2014, 343 (6176) :1221-1228.
    [21]MUN HS, LEE SA, KIM H, et al.Novel F141L pre-S2 mutation in hepatitis B virus increases the risk of hepatocellular earcionma in patients with chronic genotype C infe-ctions[J].Virology, 2011, 85 (1) :123-132.
    [22]JANG XB, LI YP, LI ZR.Research progress of HCV NS5A inhibitors[J].Acta Pharm Sin, 2016, 51 (9) :1378-1387. (in Chinese) 姜心贝, 李艳萍, 李卓荣.HCV NS5A抑制剂研究进展[J].药学学报, 2016, 51 (9) :1378-1387.
    [23]LAMBERT SM, LANGLEY DR, GARNETT JA, et al.The crystal structure of NS5A domain 1 from genotype 1a reveals new clues to the mechanism of action for dimeric HCV inhibitors[J].Protein Sci, 2014, 23 (6) :723-734.
    [24]ZHANG XL.Isolation and drug resistance of liver cancer stem like cells regulated by Akt pathway[D].Chongqing Med Univ, 2013. (in Chinese) 张小丽.肝癌干细胞样细胞的分离及其耐药性受Akt通路调节[D].重庆医科大学, 2013.
    [25] ARK CY, CHOI SH, KANG SM, et al.Nonstructural 5A protein activates beta-catenin signaling cascades:implication of hepatitis C virus-induced liver pathogenesis[J].J Hepatol, 2009, 51 (5) :853-864.
    [26]NELSON DR, COOPER JN, LALEZARI JP, et al.All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection:ALLY-3 Phase III Study[J].Hematology, 2015, 61 (4) :1127-1135.
    [27]CHAYAMA K, HAYES CN.Hepatitis C virus:how genetic variability affects pathobiology of disease[J].J Gastroenterol Hepatol, 2011, 26 (Suppl 1) :83-95.
    [28]RAIMONDI S, BRUNO S, MONDELLI MU, et al.Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development:a meta-analysis[J].J Hepatol, 2009, 50 (6) :1142-1154.
    [29]MEER AJ, VELDT BJ, FELD JJ, et al.Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis[J].JAMA, 2012, 308 (24) :2584-2593.
    [30]ZHANG X, LIU S, HU T, et al.Up-regulated microRNA-143transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression[J].Hepatology, 2009, 50 (2) :490-499.
    [31] KONG G, ZHANG J, ZHANG S, et al.Upregulated microRNA-29a by hepatitis B virus X protein enhances hepatoma cell migration by targeting PTEN in cell culture model[J].PLo S One, 2011, 6 (5) :e19518.
    [32] YUAN K, LIAN Z, SUN B, et al.Role of miR-148a in hepatitis B associated hepatocellular carcinoma[J].PLo S One, 2012, 7 (4) :e35331.
    [33]PLACE RF, LI LC, POOKOT D, et al.MicroRNA-373 induces expression of genes with complementary promoter sequences[J].Proc Natl Acad Sci U S A, 2008, 105 (5) :1608-1613.
    [34] WU G, YU F, XIAO Z, et al.Hepatitis B virus X protein downregulates expression of the miR-16 family in malignant hepatocytes in vitro[J].Br J Cancer, 2011, 105 (1) :146-153.
    [35] HUNG CH, HU TH, LU SN, et al.Circulating microRNAs as biomarkers for diagnosis of early hepatocellular carcinoma associated with hepatitis B virus[J].Int J Cancer, 2015, 138 (3) :714-720.
    [36]SHRIVASTAVA S, STEELE R, RAY R, et al.MicroRNAs:role in hepatitis C virus pathogenesis[J].Genes Dis, 2015, 2 (1) :35-45.
    [37]LI ZY, LU ZM, ZHAO XX, et al.Progress on miRNA in hepatocellular carcinoma[J/CD].Chin J Liver Dis:Electronic Edition, 2015, 7 (4) :11-13. (in chinese) 李子英, 卢再鸣, 赵相轩, 等.微小RNA与原发性肝癌的研究进展[J/CD].中国肝脏病杂志:电子版, 2015, 7 (4) :11-13.
    [38] ZHANG X, LIU S, HU T, et al.Up-regulated microRNA-143transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression[J].Hepatology, 2009, 50 (2) :490-499.
    [39]KONG G, ZHANG J, ZHANG S, et al.Upregulated microRNA-29a by hepatitis B virus X protein enhances hepatoma cell migration by targeting PTEN in cell culture model[J].PLo S One, 2011, 6 (5) :e19518.
    [40]YUAN K, LIAN Z, SUN B, et al.Role of miR-148a in hepatitis B associated hepatocellular carcinoma[J].PLo S One, 2012, 7 (4) :e35331.
    [41]FENG M, E CY, LI H, et al.Expression of miR-196a in liver cancer cells and its promotion effect on proliferation[J].J Jilin Univ:Med Edit, 2015, 41 (1) :120-124. (in Chinese) 冯默, 鄂长勇, 李航, 等.miR-196a在肝癌细胞中的表达及其促增殖作用[J].吉林大学学报:医学版, 2015, 41 (1) :120-124.
    [42]WU G, YU F, XIAO Z, et al.Hepatitis B virus X protein downregulates expression of the miR-16 family in malignant hepatocytes in vitro[J].Br J Cancer, 2011, 105 (1) :146-153.
    [43]HUNG CH, HU TH, LU SN, et al.Circulating microRNAs as biomarkers for diagnosis of early hepatocellular carcinoma associated with hepatitis B virus[J].Int J Cancer, 2016, 138 (3) :714-720.
    [44]BOREL F, KONSTANTINOVA P, JANSEN PL.Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma[J].J Hepatol, 2012, 56 (6) :1371-1383.
    [45]YUNQIAO L, VANKE H, JUN X, et al.MicroRNA-206, downregulated in hepatocellular carcinoma, suppresses cell proliferation and promotes apoptosis[J].Hepatogastroenterology, 2014, 61 (133) :1302-1307.
    [46]LIU W, XU C, WAN H, et al.MicroRNA-206 overexpression promotes apoptosis, induces cell cycle arrest and inhibits the migration of human hepatocellular carcinoma Hep G2 cells[J].Int J Mol Med, 34 (2) :420-428.
    [47]MERQUIOL E, UZI D, MUELLER T, et al.HCV causes chronic endoplasmic reticulum stress leading to adaptation and interference with the unfolded protein response[J].PLo S One, 2011, 6 (9) :e24660.
    [48]XU YX, WANG HQ, ZHAO H, et al, Hippocampal injection of beta amyloid precursor protein antibody induces neuronal degeneration and learning and memory impairment (Eglish) [J].Prog Biochem Biophys, 2011, 38 (10) :908-918. (in Chinese) 许玉霞, 王洪权, 赵红, 等.海马注射β-淀粉样蛋白前体蛋白抗体诱导神经元的退行性变及学习记忆障碍[J].生物化学与生物物理进展, 2011, 38 (10) :908-918.
    [49]XIONG JJ, ZHANG QH, ZHANG YN, et al.Study on the sustained expression of hepatitis C virus NS4B activation in Hep G2 cells by endoplasmic reticulum stress[J].Chongqing Med, 2012, 41 (6) :524-526. (in Chinese) 熊江红, 张庆华, 张艳妮, 等.持续表达的丙型肝炎病毒NS4B激活Hep G2细胞内质网应激反应的研究[J].重庆医学, 2012, 41 (6) :524-526.
    [50]DREUX M, GASTAMINZA P, WIELAND SF, et al.The autophagy machinery is required to initiate hepatitis C virus replication[J].Proc Natl Acad Sci U S A, 2009, 106 (33) :14046-14051.
    [51]LI J, LIU Y, WANG Z, et al.Subversion of cellular autophagy machinery by hepatitis B virus for viral envelopment[J].J Virol, 2011, 85 (13) :6319-6333.
    [52]ARZUMANYAN A, FRIEDMAN T, NG IO, et al.Does the hepatitis Bantigen HBx promote the appearance of liver cancer stem cells?[J].Cancer Res, 2011, 71 (10) :3701-3708.
    [53]LIN C, YANG D, JIANG Y, et al.The molecular mechanism of HBx involved in the development and regulation of hepatocellular carcinoma[J].Chin J Biochem Mol Biol, 2013, 29 (8) :704-710. (in Chinese) 林丛, 杨冬, 姜颖, 等.HBx参与肝细胞癌发生发展调控的分子机制[J].中国生物化学与分子生物学报, 2013, 29 (8) :704-710.
    [54]FAN H, ZHANG H, PASCUZZI PE, et al.Hepatitis B virus Xprotein induces Ep CAM expression via active DNA demethylation directed by Rel A in complex with EZH2 and TET2[J].Oncogene, 2016, 35 (6) :715-726.
    [55]JI J, YAMASHITA T, BUDHU A, et al.Identification of microR-NA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells[J].Hepatology, 2009, 50 (2) :472-480.
    [56]LIN LJ, ZHANG JH, WANG Y, et al.Clinicopathological significance of the expression of IMP3 and IGF2 in hepatocellular carcinoma[J].Chin J Clin Exp Pathol, 2013, 29 (4) :361-364. (in Chinese) 林黎娟, 张锦辉, 王研, 等.肝细胞癌组织中IMP3与IGF2表达对预后评估的临床病理学意义[J].临床与实验病理学杂志, 2013, 29 (4) :361-364.
    [57]XU XP, ZHANG ZG, CHE YY, et al.Detection and analysis of serum autoantibodies in patients with HBV infection[J].J Clin Hepatol, 2013, 29 (6) :441-444. (in Chinese) 徐熙鹏, 张钊冠, 车媛媛, 等.HBV感染者血清自身抗体的检测分析[J].临床肝胆病杂志, 2013, 29 (6) :441-444.
    [58]QIN LX, CHEN YL, ZHANG RS, et al.Study on the relationship between hepatitis B virus infection and serum autoantibodies in pregnant women[J].China J Modern Med, 2005, 15 (11) :1712-1714. (in Chinese) 秦立新, 陈远林, 张仁生.孕妇乙型肝炎病毒感染与血清自身抗体的相关性研究[J].中国现代医学杂志, 2005, 15 (11) :1712-1714.
    [59]DONG M, ZHOU HQ, WU JB, et al.Detection and clinical significance of serum antinuclear antibodies in patients with hepatitis B virus infection[J].Lab Med, 2012, 27 (5) :374-375. (in Chinese) 董敏, 周厚清, 吴瑾滨, 等.乙型肝炎病毒感染者血清抗核抗体检测分析及临床意义[J].检验医学, 2012, 27 (5) :374-375.
    [60]HUANG CZ, LI JY, CHEN SP, et al.Expression of IL-2, IL-4, IL-6, IFN-γand IL-17A in hepatocellular carcinoma and their relationship with HBV infection[J].Chin J Immunol, 2015, 31 (4) :527-530. (in Chinese) 黄传钟, 李洁羽, 陈淑萍, 等.IL-2、IL-4、IL-6、IFN-γ、IL-17A在肝癌组织中表达及其与乙肝病毒感染的关系[J].中国免疫学杂志, 2015, 31 (4) :527-530.
    [61]OTANI K, WATANABE T, TANIGAWA T, et al.Anti-inflammatory effects of IL-17A on Helicobacter pylori-induced gastritis[J].Biochem Biophys Res Commun, 2009, 382 (2) :252-258.
    [62]QIAO Y, HUANG F, CAO XZ, et al.Study on the correlation between high expression of AID induced by HBV infection and hepatocellular carcinoma[J].Chin J Cancer Prev Treat, 2015, 22 (1) :13-18.乔莹, 黄芬, 蔡鑫泽, 等.HBV感染诱发AID高表达与肝细胞癌变相关性研究[J].中华肿瘤防治杂志, 2015, 22 (1) :13-18.
    [63]GUO TZ, HAN LX, LUO Y, et al.Risk factors of liver cancer in patients with hepatitis B virus infection[J].Int J Virol, 2016, 23 (1) :26-28. (in Chinese) 郭铁志, 韩立新, 罗研, 等.乙型肝炎病毒感染患者肝癌发病的影响因素研究[J].国际病毒学杂志, 2016, 23 (1) :26-28.
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