Hepatit C Virüsü (HCV) ve Hepatit D Virüsü (HDV): Hepatosit Kanserine (HCC) Giden Ayrık Yollar ve Terapötik Stratejiler
Yıl 2026,
Cilt: 7 Sayı: 1, 255 - 263, 31.01.2026
Abolfazl Jafarı-sales
,
Parniya Nouri-dizaj
,
Soheyla Hosseyni-nasababad
,
Sanam Karzar-torkambour
,
Aylin Golestani
,
Zahra Ghahremani
,
Mehrdad Pashazadeh
,
Sara Naebi
Öz
Hepatit C virüsü (HCV) ve hepatit D virüsü (HDV), özellikle hepatoselüler karsinom (HCC) olmak üzere karaciğer hasarına yol açabilen iki önemli viral etkendir. HCV, kan teması yoluyla enfeksiyon oluşturan bir RNA virüsüdür ve sonunda kronik karaciğer iltihabına neden olur. Araştırmalar, HCV enfeksiyonunun genetik ve hücresel değişikliklere yol açtığını ve bunun sonucunda karaciğer kanseri (KC) riskini artırdığını göstermektedir. HDV, hem HCV'ye bağlı hem de bağımsız yollarla karaciğer hastalığını kötüleştirmede kritik bir rol oynar. Çift hepatosit hasarına yol açarak ve siroz riskini artırarak HDV, HCC insidansını önemli ölçüde yükseltir. HCV ve HDV'nin birlikte enfekte olması özellikle tehlikelidir; çünkü her iki virüs de hücresel sinyal yolaklarındaki değişiklikler, kromozomal instabilite ve hepatosit tümör baskılayıcı genlerinin inhibisyonu yoluyla hepatokarsinogenezisi teşvik eder. HDV süperenfeksiyonunu önleyen HBV aşısı ve HCV tedavisinde kullanılan doğrudan etkili antiviral ilaçlar (DAA'lar) gibi önleyici gelişmelere rağmen, virüsle ilişkili kanser yükü özellikle düşük ve orta gelirli ülkelerde yaygınlığını korumaktadır. Viral hepatit kaynaklı hepatokarsinogenezisin karmaşık moleküler mekanizmalarının anlaşılması ve HCV/HDV epidemiyolojisinin iyileştirilmesi, tanı ve tedavi için yeni fırsatlar yaratmaktadır. Bu makale, yüksek riskli popülasyonlarda erken tanı, antiviral tedavi, yenilikçi tedavi yaklaşımları ve düzenli izlemelerin HCC insidansını azaltmadaki önemini vurgulamaktadır.
Kaynakça
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Roudot-Thoraval F. Epidemiology of hepatitis C virus infection. Clinics and research in hepatology and gastroenterology. 2021;45(3):101596.
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Li H-C, Yang C-H, Lo S-Y. Hepatitis C viral replication complex. Viruses. 2021;13(3):520.
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Deng L, Solichin MR, Adyaksa DNM, Septianastiti MA, Fitri RA, Suwardan GNR, et al. Cellular Release of Infectious Hepatitis C Virus Particles via Endosomal Pathways. Viruses. 2023;15(12):2430.
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Hepatitis C Virus (HCV) and Hepatitis D Virus (HDV): Divergent Pathways to Hepatocellular Carcinoma (HCC) and Therapeutic Strategies
Yıl 2026,
Cilt: 7 Sayı: 1, 255 - 263, 31.01.2026
Abolfazl Jafarı-sales
,
Parniya Nouri-dizaj
,
Soheyla Hosseyni-nasababad
,
Sanam Karzar-torkambour
,
Aylin Golestani
,
Zahra Ghahremani
,
Mehrdad Pashazadeh
,
Sara Naebi
Öz
Hepatitis C virus (HCV) and hepatitis D virus (HDV) are two significant viral agents that can lead to hepatic injury, particularly hepatocellular carcinoma (HCC). HCV is an RNA virus that primarily leads to infection via blood contact and ultimately causes chronic liver inflammation. Studies indicate that HCV infection induces genetic and cellular alterations that subsequently increase the risk of liver cancer. HDV plays a crucial role in exacerbating liver disease through both HCV-dependent and independent pathways. By causing dual damage to hepatocytes and increasing cirrhosis risk, HDV significantly elevates HCC incidence. Coinfection with HCV and HDV is particularly hazardous, as both viruses promote hepatocarcinogenesis through alterations in cellular signaling pathways, chromosomal instability, and inhibition of tumor suppressor genes in hepatocytes. Despite preventive advances such as hepatitis B virus vaccination (which prevents HDV superinfection) and direct-acting antivirals for HCV treatment, the burden of virus-associated cancers remains prevalent, especially in low and middle-income countries. Understanding the complex molecular mechanisms underlying viral hepatitis-related hepatocarcinogenesis, along with improved epidemiology of HCV/HDV, creates new opportunities for diagnosis and treatment. This article emphasizes the importance of early detection, antiviral therapy, innovative treatment approaches, and regular surveillance in high-risk populations to reduce HCC incidence.
Kaynakça
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Man S, Luo C, Yan M, Zhao G, Ma L, Gao W. Treatment for liver cancer: From sorafenib to natural products. European journal of medicinal chemistry. 2021;224:113690.
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Anwanwan D, Singh SK, Singh S, Saikam V, Singh R. Challenges in liver cancer and possible treatment approaches. Biochimica et biophysica acta (BBA)-Reviews on cancer. 2020;1873(1):188314.
-
Gao Y-X, Yang T-W, Yin J-M, Yang P-X, Kou B-X, Chai M-Y, et al. Progress and prospects of biomarkers in primary liver cancer. International Journal of Oncology. 2020;57(1):54-66.
-
Chan LK, Tsui YM, Ho DW, Ng IO. Cellular heterogeneity and plasticity in liver cancer. Semin Cancer Biol. 2022;82:134-49.
-
El-Serag HB. Epidemiology of hepatocellular carcinoma. The liver: Biology and pathobiology. 2020:758-72.
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Paul B, Lewinska M, Andersen JB. Lipid alterations in chronic liver disease and liver cancer. JHEP reports. 2022;4(6):100479.
-
Jayachandran A, Shrestha R, Bridle KR, Crawford DHG. Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review. Hepatoma Research. 2020;6(0):8.
-
Rizzo GEM, Cabibbo G, Craxì A. Hepatitis B virus-associated hepatocellular carcinoma. Viruses. 2022;14(5):986.
-
Elgretli W, Chen T, Kronfli N, Sebastiani G. Hepatitis C virus-lipid interplay: pathogenesis and clinical impact. Biomedicines. 2023;11(2):271.
-
Rumgay H, Ferlay J, de Martel C, Georges D, Ibrahim AS, Zheng R, et al. Global, regional and national burden of primary liver cancer by subtype. European Journal of Cancer. 2022;161:108-18.
-
Wang C, Cao Y, Yang C, Bernards R, Qin W. Exploring liver cancer biology through functional genetic screens. Nature reviews Gastroenterology & hepatology. 2021;18(10):690-704.
-
Galicia-Moreno M, Silva-Gomez JA, Lucano-Landeros S, Santos A, Monroy-Ramirez HC, Armendariz-Borunda J. Liver cancer: therapeutic challenges and the importance of experimental models. Canadian Journal of Gastroenterology and Hepatology. 2021;2021(1):8837811.
-
Li Q, Cao M, Lei L, Yang F, Li H, Yan X, et al. Burden of liver cancer: From epidemiology to prevention. Chinese Journal of Cancer Research. 2022;34(6):554.
-
Mazzola S, Vittorietti M, Fruscione S, De Bella DD, Savatteri A, Belluzzo M, et al. Factors Associated with Primary Liver Cancer Survival in a Southern Italian Setting in a Changing Epidemiological Scenario. Cancers. 2024;16(11):2046.
-
Mohammadian M, Mahdavifar N, Mohammadian-Hafshejani A, Salehiniya H. Liver cancer in the world: epidemiology, incidence, mortality and risk factors. World Cancer Res J. 2018;5(2):e1082.
-
Capasso M, Cossiga V, Guarino M, Ranieri L, Morisco F. The role of hepatitis viruses as drivers of Hepatocancerogenesis. Cancers. 2024;16(8):1505.
-
Osiowy C, Swidinsky K, Haylock-Jacobs S, Sadler MD, Fung S Wong D, et al. Molecular epidemiology and clinical characteristics of hepatitis D virus infection in Canada. JHEP Reports. 2022;4(5):100461.
-
Roudot-Thoraval F. Epidemiology of hepatitis C virus infection. Clinics and research in hepatology and gastroenterology. 2021;45(3):101596.
-
Li H-C, Yang C-H, Lo S-Y. Hepatitis C viral replication complex. Viruses. 2021;13(3):520.
-
Tréguier Y, Bull-Maurer A, Roingeard P. Apolipoprotein E, a Crucial Cellular Protein in the Lifecycle of Hepatitis Viruses. International Journal of Molecular Sciences. 2022;23(7):3676.
-
Saraceni C, Birk J. A review of hepatitis B virus and hepatitis C virus immunopathogenesis. Journal of Clinical and Translational Hepatology. 2021;9(3):409.
-
Roudot-Thoraval F. Epidemiology of hepatitis C virus infection. Clin Res Hepatol Gastroenterol. 2021;45(3):101596.
-
Liu C-H, Kao J-H. Acute hepatitis C virus infection: clinical update and remaining challenges. Clinical and molecular hepatology. 2023;29(3):623.
-
Farci P, Niro GA, Zamboni F, Diaz G. Hepatitis D virus and hepatocellular carcinoma. Viruses. 2021;13(5):830.
-
Pérez-Vargas J, Pereira de Oliveira R, Jacquet S, Pontier D, Cosset F-L, Freitas N. HDV-like viruses. Viruses. 2021;13(7):1207.
-
Alvarado-Mora MV, Locarnini S, Rizzetto M, Pinho JRR. An update on HDV: virology, pathogenesis and treatment. Antiviral therapy. 2013;18(3_part_2):541-8.
-
Abbas Z, Afzal R. Life cycle and pathogenesis of hepatitis D virus: A review. World journal of hepatology. 2013;5(12):666.
-
Dziri S, Rodriguez C, Gerber A, Brichler S, Alloui C, Roulot D, et al. Variable in vivo hepatitis D virus (HDV) RNA editing rates according to the HDV genotype. Viruses. 2021;13(8):1572.
-
Karimzadeh H, Usman Z, Frishman D, Roggendorf M. Genetic diversity of hepatitis D virus genotype-ı in Europe allows classification into subtypes. Journal of Viral Hepatitis. 2019;26(7):900-10.
-
Thiyagarajah K, Basic M, Hildt E. Cellular factors involved in the hepatitis D virus life cycle. Viruses. 2023;15(8):1687.
-
Puigvehí M, Moctezuma-Velázquez C, Villanueva A, Llovet JM. The oncogenic role of hepatitis delta virus in hepatocellular carcinoma. JHEP Reports. 2019;1(2):120-30.
-
Almeida PH, Matielo CE, Curvelo LA, Rocco RA, Felga G, Della Guardia B, et al. Update on the management and treatment of viral hepatitis. World journal of gastroenterology. 2021;27(23):3249.
-
Shen C, Jiang X, Li M, Luo Y. Hepatitis virus and hepatocellular carcinoma: recent advances. Cancers. 2023;15(2):533.
-
Li H-C, Yang C-H, Lo S-Y. Cellular factors involved in the hepatitis C virus life cycle. World Journal of Gastroenterology. 2021;27(28):4555.
-
Chu Y-D, Chen M-C, Yeh C-T, Lai M-W. Hijacking host extracellular vesicle machinery by hepatotropic viruses: current understandings and future prospects. Journal of Biomedical Science. 2024;31(1):97.
-
Deng L, Solichin MR, Adyaksa DNM, Septianastiti MA, Fitri RA, Suwardan GNR, et al. Cellular Release of Infectious Hepatitis C Virus Particles via Endosomal Pathways. Viruses. 2023;15(12):2430.
-
Romero-López C, Berzal-Herranz A. The role of the RNA-RNA interactome in the hepatitis C virus life cycle. International Journal of Molecular Sciences. 2020;21(4):1479.
-
Suarez B, Prats-Mari L, Unfried JP, Fortes P. LncRNAs in the type I interferon antiviral response. International Journal of Molecular Sciences. 2020;21(17):6447.
-
Carriquí-Madroñal B, Lasswitz L, von Hahn T, Gerold G. Genetic and pharmacological perturbation of hepatitis-C virus entry. Current opinion in virology. 2023;62:101362.
-
Deest M, Westhaus S, Steinmann E, Manns MP, von Hahn T, Ciesek S. Impact of single nucleotide polymorphisms in the essential HCV entry factor CD81 on HCV infectivity and neutralization. Antiviral research. 2014;101:37-44.
-
Gerold G, Meissner F, Bruening J, Welsch K, Perin PM, Baumert TF, et al. Quantitative proteomics identifies serum response factor binding protein 1 as a host factor for hepatitis C virus entry. Cell reports. 2015;12(5):864-78.
-
Colpitts CC, Tsai P-L, Zeisel MB. Hepatitis C virus entry: an intriguingly complex and highly regulated process. International journal of molecular sciences. 2020;21(6):2091.
-
Lee GS, Purdy MA, Choi Y. Cell Culture systems for studying Hepatitis B and Hepatitis D Virus infections. Life. 2023;13(7):1527.
-
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