Abstract
Hepatocellular carcinoma (HCC), the major manifestation of primary liver cancer, is one of the most frequent and malignant diseases worldwide. Among other environmental factors, hepatitis viruses, as the hepatitis B (HBV) and hepatitis C (HCV) viruses, are to be listed in the etiology of HCC. Both of these viruses cause a wide spectrum of clinical manifestations, ranging from healthy carrier state to acute and chronic hepatitis, cirrhosis and HCC. HBV and HCV are different viruses in structure: HBV contains a DNA genome which replicates through an RNA intermediate and requires an active viral reverse transcriptase (RT) polymerase enzyme, while HCV is an RNA virus which has no RT activity and replicates on the cellular membrane by RNA replication. In this review we discuss how these two biologically diverse viruses use common pathways to induce hepatocarcinogenesis despite their significant structural and viral cycle differences. A summary is also given of several observable common and different features. Direct integration of HBV viral sequences into the host genome increases the genomic instability, which does not occur in HCV infection. However, viral proteins may directly play a significant role in the induction of carcinogenesis by both viruses.
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Abbreviations
- STAT 3:
-
signal transducer and activator of transcription 3
- IGF:
-
insulin-like growth factor
- PKC:
-
protein kinase C
- NFB:
-
nuclear factor kappa
References
Agnello V, Abel G, Elfahal M et al: Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci USA 96: 12766–12771, 1999
Aizawa Y, Shibamoto Y, Takagi I et al: Analysis of factors affecting the appearance of hepatocellular carcinoma in patients with chronic hepatitis C. Cancer 89: 53–59, 2000
Andrisani OM, Barnabas S: The transcriptional function of the hepatitis B virus X protein and its role in hepatocarcinogenesis. Int J Oncol 15: 373–379, 1999
Anthony PP: Hepatocellular carcinoma: an overview. Histopathology 39: 109–118, 2001
Bosch FX: Global epidemiology of hepatocellular carcinoma. In: Liver Cancer. (Eds: Okuda K, Tabor E), Churchill Livingstone, New York, 1997, pp. 13–28
Bréchot C, Gozuacik D, Murakami Y et al: Molecular bases for the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Semin Cancer Biol 10: 211–231, 2000
Buendia MA: Genetics of hepatocellular carcinoma. Semin Cancer Biol 10: 185–200, 2000
Chen P-J, Chen D-S: Hepatitis B virus infection and hepatocellular carcinoma: Molecular genetics and clinical perspectives. Semin Liver Dis 19: 253–262, 1999
Cohen J: The scientific challenge of hepatitis C. Science 285: 26–30, 1999
Conjeevaram HS, Lok AS: Management of chronic hepatitis B. J Hepatol 38: S90-S103, 2003
Edamoto Y, Hara A, Biernat W et al: Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis. Int J Cancer 106: 334–341, 2003
El-Serag HB, Mason AC, Key C: Trends in survival of patients with hepatocellular carcinoma between 1977 and 1996 in the United States. Hepatology 3: 62–65, 2001
Faivre J, Forman D, Estève J et al: Survival of patients with primary liver cancer, pancreatic cancer and biliary tract cancer in Europe. EUROCARE Working Group. Eur J Cancer 34: 2184–2190, 1998
Feitelson MA: Hepatitis B virus in hepatocarcinogenesis. J Cell Physiol 181: 188–202, 1999
Feo F, Pascale RM, Simile MM et al: Genetic alterations in liver carcinogenesis: implications for new preventive and therapeutic strategies. Crit Rev Oncogen 11: 19–62, 2000
Ferber MJ, Montoya DP, Yu C et al: Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (h TERT) gene in liver and cervical cancers. Oncogene 22: 3813–3820, 2003
Ferlay J, Bray F, Pisani P et al: GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide, Version 1.0., IARC CancerBase No. 5, IARC Press, Lyon, 2001
Gelatti U, Donato F, Tagger A et al: Etiology of hepatocellular carcinoma influences clinical and pathologic features but not patient survival. Am J Gastroenterol 98: 907–914, 2003
Giannelli G, Fransvea E, Marinosci F et al: Transforming growth factor-1 triggers hepatocellular carcinoma invasiveness via 31 integrin. Am J Pathol 161: 183–193, 2002
Idilman R, DeMaria N, Colantoni A et al: Pathogenesis of hepatitis B and C-induced hepatocellular carcinoma. J Viral Hepat 5: 285–299, 1998
Iizuka N, Oka M, Yamada-Okabe H et al: Differential gene expression in distinct virologic types of hepatocellular carcinoma: association with liver cirrhosis. Oncogene 22: 3007–3014, 2003
Laurent-Puig P, Legoix P, Bluteau O et al: Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis. Gastroenterology 120: 1763–1773, 2001
Moradpour D, Wands JR: Molecular pathogenesis of hepatocellular carcinoma. In: Hepatology. A Textbook of Liver Disease, ed 4. (Eds: Zakim D, Boyer TD), Saunders, Philadelphia, 2003, pp. 1333–1354
Nair S, Perrillo RP: Hepatitis B and D. In: Hepatology. A Textbook of Liver Disease, ed 4. (Eds: Zakim D, Boyer TD), Saunders, Philadelphia, 2003, pp. 959–1016
Nakamoto Y, Kanekos S: Mechanisms of viral hepatitis induced liver injury. Curr Mol Med 3: 537–544, 2003
Ochiai T, Urata Y, Yamano T et al: Clonal expansion in evolution of chronic hepatitis to hepatocellular carcinoma as seen at an X-chromosome locus. Hepatology 31: 615–621, 2000
Okuda K: Hepatocellular carcinoma. J Hepatol 32 (Suppl 1): 225–237, 2000
Ozturk M: Genetic aspects of hepatocellular carcinogenesis. Semin Liver Dis 19: 235–242, 1999
Paradis V, Bièche I, Dargère D et al: Molecular profiling of hepatocellular carcinomas (HCC) using a large-scale real-time RT-PCR approach. Am J Pathol 163: 733–741, 2003
Parkin DM, Bray FI, Devesa SS: Cancer burden in the year 2000. The global picture. Eur J Cancer 37: S4-S66, 2001
Pileri P, Uematsu Y, Campagnoli S et al: Binding of hepatitis C virus to CD81. Science 282: 938–941, 1998
Pina Dore M, Realdi G, Mura D et al: Genomic instability in chronic viral hepatitis and hepatocellular carcinoma. Hum Pathol 32: 698–703, 2001
Pineau P andBuendia MA: Studies of genetic defects in hepatocellular carcinoma: recent outcomes and new challenges. J Hepatol 33: 152–156, 2000
Poussin K, Dienes H, Sirma H et al: Expression of mutated hepatitis B virus X genes in human hepatocellular carcinomas. Int J Cancer 80: 497–505, 1999
Qui W, David D, Zhou B et al: Down-regulation of growth arrest DNA damage-inducible gene 45 expression is associated with human hepatocellular carcinoma. Am J Pathol 162: 1961–1974, 2003
Rosen HR, Gretch DR: Hepatitis C virus: current understanding and prospects for future therapies. Mol Med Today 5: 393–399, 1999
Saunier B, Triyatni M, Ulianich L et al: Role of the asialoglycoprotein receptor in binding and entry of hepatitis C virus structural proteins in cultured human hepatocytes. J Virol 77: 546–559, 2003
Scarselli E, Ansuini H, Cerino R et al: The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J 21: 5017–5025, 2002
Schulze zur Wiesch J, Schmitz H, Borowski E, Borowski P: The proteins of the hepatitis C virus: Their features and interactions with intracellular protein phosphorylation. Arch Virol 148: 1247–1267, 2003
Szabó E, Lotz G, Páska C et al: Viral hepatitis: New data on hepatitis C. Pathol Oncol Res 9: 215–221, 2003
Tabor E: Interferon for preventing and treating hepatocellular carcinoma associated with the hepatitis B and C viruses. Dig Liver Dis 35: 297–305, 2003
Thorgeirsson SS, Grisham JW: Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 31: 339–346, 2002
Torbenson M, Marinopoulos S, Dang DT et al: Smad4 overexpression in hepatocellular carcinoma is strongly associated with transforming growth factor beta II receptor immunolabeling. Hum Pathol 33: 871–876, 2002
Tornillo L, Carafa V, Richter J et al: Marked genetic similarities between hepatitis B virus-positive and hepatitis C viruspositive hepatocellular carcinomas. J Pathol 192: 307–312, 2000
van Regenmortel MHV, Fauquet CM, Bishop DHL et al: Virus Taxonomy. The VIIth Report of the International Committee on Taxonomy of Viruses. Academic Press, San Diego, 2000
Wagayama, H, Shiraki K, Sugimoto K et al: High expression of p21WAF1/CIP1 is correlated with human hepatocellular carcinoma in patients with hepatitis C virus-associated chronic liver diseases. Hum Pathol 33: 429–434, 2002
Waris G, Siddiqui A: Regulatory mechanisms of viral hepatitis B and C. J Biosci 28: 311–321, 2003
Xu X-R, Huang J, Xu Z-G et al: Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver. Proc Natl Acad Sci USA 98: 15089–15094, 2001
Ye Q-H, Qin L-X, Forgues M et al: Predicting hepatitis B viruspositive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat Med 9: 416–423, 2003
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This work has been supported by grants Bio-00014/2001, ETT-077/2003, NKFP-1A/0023/2002 and OTKA T 037838
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Szabó, E., Páska, C., Novák, P.K. et al. Similarities and differences in hepatitis B and C virus induced hepatocarcinogenesis. Pathol. Oncol. Res. 10, 5–11 (2004). https://doi.org/10.1007/BF02893401
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DOI: https://doi.org/10.1007/BF02893401