HBV and HCV as Risk Factors for Hepatocellular Carcinoma
Article Sidebar
Main Article Content
Abstract
Hepatocellular liver cancer (HCC) is associated with a high incidence of chronic hepatitis B and C aetiology. Hepatocellular cancer must not always be preceded by cirrhotic liver disease. In the pathogenesis of cirrhosis, the liver is dominated by three pathological processes, including hepatocyte necrosis (cell death), fibrosis and regeneration. Cirrhosis, with its histological characteristics, is a precancerous condition that leads to the development of cancer. Viruses B or C, in their presence in the liver parenchyma, trigger an inflammatory process followed by hepatocyte necrosis. Chronic active hepatitis B and C aetiology is a major medical problem since viruses, by their presence and incorporation in the hepatocyte genome, trigger the pathological process leading to HCC. Alpha-fetoprotein (AFP) is the most important diagnostic marker for HCC. It has relatively high specificity and sensitivity and is widely applied in practice. With this research, we will point out all known facts about the increase of Hepatocellular carcinoma (HCC) in men and women with hepatitis B and C aetiology. The research highlights the importance of diagnosing hepatitis, the polymerase chain reaction, and the serological reaction very important for the quantification of the virus in the serum of the diseased, as well as the histological findings of the liver obtained by taking a biopsy sample by percutaneous liver biopsy. A particular review is given on the epidemiological significance of hepatitis, as viral infections spread throughout the Earth's sphere, as well as viruses declared to be biological carcinogens. Also, the research has given great importance to AFP as a significant carcinoma antigen in diagnosing HCC.
Article Details
Copyright (c) 2026 Bilic-Komarica E.
This work is licensed under a Creative Commons Attribution 4.0 International License.
1. Regev A, Schiff ER. Viral hepatitis A, B, and C. J Gastrointest Surg. 2005;8(7):794 805.
2. Biron C. Initial and innate responses to viral infections: pattern setting in immunity or disease. Curr Opin Microbiol. 1999;2(4):374 81. Available from: https://doi.org/10.1016/s1369-5274(99)80066-6
3. Dautović Krkić S. Virusni hepatitisi. In: Infektologija. Sarajevo Tuzla; 2011. p. 293 301.
4. Balsano C, Avantaggiati ML, Natoli G, De Marzio E, Will H, Perricaudet M, et al. Full length and truncated versions of the hepatitis B virus (HBV) X protein (pX) transactivate the c myc protooncogene at the transcriptional level. Biochem Biophys Res Commun. 1991;178(3):985 92. Available from: https://doi.org/10.1016/0006-291x(91)90379-l
5. Hsing AW, Zhang M, Rashid A, McGlynn KA, Wang BS, Niwa S, et al. Hepatitis B and C virus infection and the risk of biliary tract cancer: a population based study in China. Int J Cancer. 2008;122(8):1849 53. Available from: https://doi.org/10.1002/ijc.23251
6. Amin J, Dore GJ, O’Connell DL, Bartlett M, Tracey E, Kaldor JM, et al. Cancer incidence in people with hepatitis B or C infection: a large community based linkage study. J Hepatol. 2006;45(2):197 203. Available from: https://doi.org/10.1016/j.jhep.2006.02.014
7. Afdhal NH, Nunes D. Evaluation of liver fibrosis: a concise review. Am J Gastroenterol. 2004;99(6):1160 74. Available from: https://doi.org/10.1111/j.1572-0241.2004.30110.x
8. Miyake Y, Takaki A, Iwasaki Y, Yamamoto K. Meta analysis: interferon alpha prevents recurrence after curative treatment of hepatitis C virus related hepatocellular carcinoma. J Viral Hepat. 2010;17(4):287 92. Available from: https://doi.org/10.1111/j.1365-2893.2009.01181.x
9. Rustemović N. Maligni tumori jetre. Gastroenterologija i Hepatologija. 2002:1355 74.
10. Ahmetagić S. Virusni hepatitisi. In: Infektologija. Sarajevo Tuzla; 2011. p. 301 6.
11. Asselah T, Ripault MP, Castelnau C, Giuly N, Marcellin P. The current status of antiviral therapy of chronic hepatitis. J Clin Virol. 2005;34 Suppl 1:S115 24. Available from: https://doi.org/10.1016/s1386-6532(05)80020-4
12. Miyake Y, Takaki A, Iwasaki Y, Yamamoto K. Meta analysis: interferon alpha prevents recurrence after curative treatment of hepatitis C virus related hepatocellular carcinoma. J Viral Hepat. 2010;17(4):287 92. Available from: https://doi.org/10.1111/j.1365-2893.2009.01181.x
13. El Serag HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology. 2004;127(5 Suppl 1):S27 34. Available from: https://doi.org/10.1053/j.gastro.2004.09.013
14. Mohammed R, Yuen MF, Kao J, Lim SG. Prevention of hepatocellular carcinoma in hepatitis B virus infection. Gastroenterol Hepatol. 2009.
15. Omer RE, Veer PV, Kadaru AMY, Kampman E, El Khidir IM, Fedail SS, et al. The role of hepatitis B and hepatitis C viral infections in the incidence of hepatocellular carcinoma in Sudan. J Hepatol. 2006;45(4):529 38.
16. Chang MH, Chen DS. Prevention of hepatocellular carcinoma by hepatitis B immunisation. Taipei: College of Medicine, National Taiwan University; 2003.
17. Kasahara A, Hayashi N, Mochizuki K, Takayanagi M, Yoshioka K, Kakumu S, et al. Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. J Hepatol. 1998;27(5):1394 402. Available from: https://doi.org/10.1002/hep.510270529
18. Strauss R, Torner A, Duberg AS, Hultcrantz R, Ekdahl K. Hepatocellular carcinoma and other primary liver cancers in hepatitis C patients in Sweden: a low endemic country. J Viral Hepat. 2008;15(7):531 7. Available from: https://doi.org/10.1111/j.1365-2893.2008.00979.x
19. Davila JA, Henderson L, Kramer JR, Kanwal F, Richardson PA, Duan Z, et al. Screening for liver cancer in patients with hepatitis C virus infection and cirrhosis. Ann Intern Med. 2010.
20. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, et al. Clinical management of hepatocellular carcinoma: conclusions of the Barcelona 2000 EASL conference. J
21. Baig JA, Alam JM, Mahmood SR, Baig M, Shaheen R, Sultana I, et al. Hepatocellular carcinoma and diagnostic significance of alpha fetoprotein. J Ayub Med Coll Abbottabad. 2009;21(1):72 5. Available from: https://pubmed.ncbi.nlm.nih.gov/20364746/
22. Tangkijvanich P, Mahachai V, Suwangool P, Poovorawan Y. Gender difference in clinicopathologic features and survival of patients with hepatocellular carcinoma. World J Gastroenterol. 2004;10(11):1547 50. Available from: https://doi.org/10.3748/wjg.v10.i11.1547
23. Peng SY, Chen WJ, Lai PL, Jeng YM, Sheu JC, Hsu HC. High α fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and β catenin mutations. Int J Cancer. 2004;112(1):44 50. Available from: https://doi.org/10.1002/ijc.20279
24. Tsuchiya M, Parker JS, Kono H, Matsuda M, Fujii H, Rusyn I. Gene expression in nontumoral liver tissue and recurrence free survival in hepatitis C virus positive hepatocellular carcinoma. Mol Cancer. 2010;9:74. Available from: https://doi.org/10.1186/1476-4598-9-74
25. Shuhei Y, Kazutaka K, Keiji A, Tsutomu M, Naoki T, Toshiharu F, et al. Clinical significance of lens culinaris agglutinin reactive fraction of serum α fetoprotein in patients with hepatocellular carcinoma. Jpn J Gastroenterol Hepatol. 2002.
26. Strauss R, Torner A, Duberg AS, Hultcrantz R, Ekdahl K. Hepatocellular carcinoma and other primary liver cancers in hepatitis C patients in Sweden: a low endemic country. J Viral Hepat. 2008;15(7):531 7. Available from: https://doi.org/10.1111/j.1365-2893.2008.00979.x
27. Bui Nguyen TM, Pakala SB, Sirigiri RD, Xia W, Hung MC, Sarin SK, et al. NF κB signalling mediates the induction of MTA1 by hepatitis B virus transactivator protein HBx. Oncogene. 2010;29(8):1179 89. Available from: https://doi.org/10.1038/onc.2009.404
28. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516652/
29. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651909/
30. Available from: http://www.doiserbia.nb.rs/ft.aspx?id=0025-810514031R
31. Singal AG, Llovet JM, Yarchoan M, Mehta N, Heimbach JK, Dawson LA, et al. AASLD practice guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology. 2023;78(6):1922 65. Available from: https://doi.org/10.1097/hep.0000000000000466
32. Park S, Davis AM, Pillai AA. Prevention, diagnosis, and treatment of hepatocellular carcinoma. JAMA. 2024;332(12):1013 4. Available from: https://doi.org/10.1001/jama.2024.14101
33. Seth I, Siu A, Hewitt L, Budak U, Farah B, et al. Clinical practice guidelines for the management of hepatocellular carcinoma: a systematic review. J Gastrointest Cancer. 2024;55(2):318 31. Available from: https://doi.org/10.1007/s12029-023-00961-0
34. Suddle A, Reeves H, Hubner R, Marshall A, Rowe I, Tiniakos D, et al. British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults. Gut. 202.
35. Teng W, Wang HW, Lin SM, et al. Management Consensus Guidelines for Hepatocellular Carcinoma: 2023 Update on Surveillance, Diagnosis, Systemic Treatment, and Post-treatment Monitoring. Liver Cancer, 2024.
36. World Health Organization. Guidelines for the prevention, diagnosis, care and treatment for people with chronic hepatitis B infection. Geneva: WHO; 2024.
37. European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines on the Management of Liver Diseases and Hepatocellular Carcinoma. Journal of Hepatology, 2023.
38. Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6. Available from: https://doi.org/10.1038/s41572-020-00240-3
39. Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019 Apr 11;380(15):1450-1462. Available from: https://doi.org/10.1056/nejmra1713263
40. Global Burden of Disease Liver Cancer Collaboration. Global Burden of Primary Liver Cancer and Its Etiological Factors in 204 Countries and Territories. The Lancet Gastroenterology & Hepatology, 2023.