Identification of hepatitis B virus mutations in patients with hepatocellular carcinoma
https://doi.org/10.51793/OS.2025.28.2.006
Abstract
Background. Hepatocellular carcinoma is one of the most serious healthcare issues, particularly in the context of hepatitis B virus infection. Hepatitis B virus is associated with a high risk of developing hepatocellular carcinoma, and there is evidence that certain mutations in the viral genome may increase this risk. However, studies conducted on the Russian population remain insufficient.
Objective. The aim of this study is to identify hepatitis B virus mutations that may be associated with an increased risk of developing hepatocellular carcinoma in patients of the Russian population.
Materials and methods. The study included 7 male patients diagnosed with hepatocellular carcinoma secondary to hepatitis B and a control group of 30 participants. Viral genomes were determined using the latest generation sequencing panel HBV-seq. Statistical analysis was performed using Pearson's χ² test.
Results. All viral genomes analyzed were genotype D, which is the most prevalent in Russia. Several mutations were identified in the hepatocellular carcinoma patient group that occurred significantly more frequently compared to the control group. These include: Core protein (C-protein): cT67N, cP130Q/L; Polymerase protein (P-protein): pT66S, pT239A, pS285A, pH289C/P, pL335H/I, pN388D, pL450M, pC667R/Y. Additionally, oncogenic mutations xK130M and xV131I were found in 3 out of 7 patients, cA80I/T in 2 out of 7, as well as single cases of mutations sP120T and sY134F.
Conclusion. The results of the present study demonstrate high genetic variability among patients with hepatocellular carcinoma. Determining the significance of specific hepatitis B virus mutations and their associations with hepatocellular carcinoma development represents an important direction for further research in the field of medicine.
Keywords
About the Authors
A. A. GrishaevaRussian Federation
Antonina A. Grishaeva, Cand. of Sci. (Med.), Researcher of the Clinical Department of Infectious Pathology
3a Novogireevskaya str., Moscow, 111123
M. D. Chanyshev
Russian Federation
Mikhail D. Chanyshev, Cand. of Sc. (Biol.), Senior Researcher, Laboratory for Genomic Research
3a Novogireevskaya str., Moscow, 111123
A. G. Glushchenko
Russian Federation
Albina G. Glushchenko, laboratory research assistant, Laboratory for Genomic Research
3a Novogireevskaya str., Moscow, 111123
V. V. Makashova
Russian Federation
Vera V. Makashova, Dr. of Sci. (Med.), Leading Researcher, Clinical Department of Infectious Diseases
3a Novogireevskaya str., Moscow, 111123
A. S. Chernyshova
Russian Federation
Anastasia S. Chernyshova, laboratory assistant of Laboratory for Genomic Research
3a Novogireevskaya str., Moscow, 111123
K. F. Khafizov
Russian Federation
Kamil F. Khafizov, Cand. of Sc. (Biol.), Head of Laboratory for Genomic Research
3a Novogireevskaya str., Moscow, 111123
Zh. B. Ponezheva
Russian Federation
Zhanna B. Ponezheva, Dr. of Sci. (Med.), Head of the Clinical Department of Infectious Diseases
3a Novogireevskaya str., Moscow, 111123
References
1. El-Serag H. B., Rudolph K. L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007; 132: 2557-2576.
2. Venook A. P., Papandreou C., Furuse J., de Guevara L. L. The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist. 2010; 15: 5-13.
3. Cancer IARC. Globocan. Estimated cancer incidence, mortality and prevalence worldwide in 2012. World Health Organization; 2012. 9, http://globocaniarc fr/Pages/fact_sheets_cancer aspx.
4. Fattovich G., Stroffolini T., Zagni I., Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004; 127: S35-S50.
5. Sherman M. Risk of hepatocellular carcinoma in hepatitis B and prevention through treatment. Cleve Clin J Med. 2009; 76: S6-S9.
6. Chan H. L., Hui A. Y., Wong M. L., Tse A. M., Hung L. C., Wong V. W., et al. Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma. Gut. 2004; 53: 1494-1498.
7. Kuang S. Y., Jackson P. E., Wang J. B., et al. Specific mutations of hepatitis B virus in plasma predict liver cancer development. Proc Natl Acad Sci USA. 2004; 101: 3575-3580.
8. Pollicino T., Cacciola I., Saffioti F., Raimondo G. Hepatitis B virus PreS/S gene variants: pathobiology and clinical implications. J Hepatol. 2014; 61: 408-417.
9. Liu S., Zhang H., Gu C., Yin J., He Y., Xie J., et al. Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis. J Natl Cancer Inst. 2009; 101: 1066-1082.
10. Chen C. H., Hung C. H., Lee C. M., Hu T. H., Wang J. H., Wang J. C., et al. Pre-S deletion and complex mutations of hepatitis B virus related to advanced liver disease in HBeAg-negative patients. Gastroenterology. 2007; 133: 1466-1474.
11. Bruss V. Revisiting the cytopathic effect of hepatitis B virus infection. Hepatology. 2002; 36: 1327-1329.
12. Warner N., Locarnini S. The antiviral drug selected hepatitis B virus rtA181T/ sW172⁄ mutant has a dominant negative secretion defect and alters the typical profile of viral rebound. Hepatology. 2008; 48: 88-98.
13. Jiang D.-K., Sun J., Cao G., et al. Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. Nat Genet. 2013; 45: 72-75.
14. Ning Q., Yang T., Guo X., Huang Y., Gao Y., Liu M., Yang P., Guan Y., Liu N., Wang Y., Chen D. CHB patients with rtA181T-mutated HBV infection are associated with higher risk hepatocellular carcinoma due to increases in mutation rates of tumour suppressor genes. J Viral Hepat. 2023; 30 (12): 951-958. DOI: 10.1111/jvh.13886. Epub 2023 Sep 21. PMID: 37735836.
15. Ostankova Yu. V., Serikova E. N., Semenov A. V., Zueva E. B., Valutite D. E., Schemelev A. N., Zurochka V. A., Totolyan A. A. Molecular and genetic characterization of the hepatitis B virus full-length genome sequences identified in HBsAg-negative blood donors in Ural Federal District. Zhurnal mikrobiologii, èpidemiologii i immunobiologii. 2022; 99 (6): 637-650. (In Russ.) DOI: https://doi.org/10.36233/0372-9311-325
16. Ostankova Yu. V., Semenov A. V. , Totolian Areg A. Hepatitis B virus identification in a blood plasma at a low viral load. Klinicheskaya Laboratornaya Diagnostika. 2019; 64 (10): 635-640 (In Russ.) DOI: http://dx.doi.org/10.18821/0869-2084-2019-64-10-635-640
17. Чанышев М. Д., Власенко Н. В., Роев Г. В., Котов И. А., Глущенко А. Г., Макашова В. В., Хафизов К. Ф., Акимкин В. Г. Амплификационная панель NGS для секвенирования ДНК вируса гепатита В (Hepadnaviridae: Orthohepadnavirus). Вопросы вирусологии. 2024; 1 (69): 65-75. DOI: 10.36233/0507-4088-212.
18. Al-Qahtani A. A., Al-Anazi M. R., Nazir N., Abdo A. A., Sanai F. M., Al-Hamoudi W. K., Alswat K. A., Al-Ashgar H. I., Khan M. Q., Albenmousa A., El-Shamy A., Alanazi S. K., Dela Cruz D., Bohol M. F. F., Al-Ahdal M. N. The Correlation Between Hepatitis B Virus Precore/Core Mutations and the Progression of Severe Liver Disease. Front Cell Infect Microbiol. 2018; 8: 355. DOI: 10.3389/fcimb.2018.00355. PMID: 30406036; PMCID: PMC6204459.
19. Sanaei N., Hashemi S. M. A., Dehno S. Z. S., Asl M. M., Moini M., Malek-Hosseini S. A., Hosseini S. Y., Sarvari J. Precore/core mutations of hepatitis B virus genotype D arising in different states of infection. Clin Exp Hepatol. 2022; 8 (1): 21-28. DOI: 10.5114/ceh.2022.114253. Epub 2022 Mar 23. PMID: 35415256; PMCID: PMC8984791.
20. Al-Qahtani A. A., Al-Anazi M. R., Nazir N., Ghai R., Abdo A. A., Sanai F. M., Al-Hamoudi W. K., Alswat K. A., Al-Ashgar H. I., Khan M. Q., Albenmousa A., Cruz D. D., Bohol M. F. F., Al-Ahdal M. N. Hepatitis B virus (HBV) X gene mutations and their association with liver disease progression in HBVinfected patients. Oncotarget. 2017; 8 (62): 105115-105125. DOI: 10.18632/oncotarget.22428. PMID: 29285238; PMCID: PMC5739625.
21. Lin X., Xu X., Huang QL., Liu Y. Q., Zheng D. L., Chen W. N., Lin J. Y. Biological impacts of "hot-spot" mutations of hepatitis B virus X proteins are genotype B and C differentiated. World J Gastroenterol. 2005; 11 (30): 47034708. DOI: 10.3748/wjg.v11.i30.4703. PMID: 16094714; PMCID: PMC4615415.
22. Coppola N., Onorato L., Minichini C., Di Caprio G., Starace M., Sagnelli C., Sagnelli E. Clinical significance of hepatitis B surface antigen mutants. World J Hepatol. 2015; 7 (27): 2729-2739. DOI: 10.4254/wjh.v7.i27.2729. PMID: 26644816; PMCID: PMC4663392.
Review
For citations:
Grishaeva A.A., Chanyshev M.D., Glushchenko A.G., Makashova V.V., Chernyshova A.S., Khafizov K.F., Ponezheva Zh.B. Identification of hepatitis B virus mutations in patients with hepatocellular carcinoma. Lechaschi Vrach. 2025;(2):38-43. (In Russ.) https://doi.org/10.51793/OS.2025.28.2.006
JATS XML



















