Frequency of polymorphic variants of the IFNG (rs2069705) and IL28b (rs12979860) genes depending on the severity of clinical manifestations of Opisthorchis felineus invasion

Introduction. The study of the role of cytokines in cellular interactions in liver diseases is currently given great importance. However, studies in this area in patients with Opisthorchis felineus (O. felineus) invasion are still limited.

Aim. To study the relationship between laboratory and instrumental manifestations of pathology with polymorphisms of the genes IFNG (rs2069705) and IL28b (rs12979860) in patients with O. felineus invasion.

Materials and methods. A total of 360 patients with O. felineus invasion (170 men and 192 women, mean age 42.1 ± 0.7 years) and 124 control group individuals (65 men and 59 women, mean age 48.3 ± 1.1 years) were examined. O. felineus invasion was diagnosed using duodenal bile microscopy and coproovoscopy. All patients underwent complete blood count, biochemical blood test, abdominal ultrasound, and liver elastometry with liver fibrosis assessment using the METAVIR scale. Genotyping of single nucleotide polymorphisms of the genes IFNG (rs2069705) and IL28b (rs12979860) was performed using real-time PCR. Results. In patients with O. felineus invasion, liver fibrosis was associated with the heterozygous TC genotype for the rs2069705 IFNG polymorphism. Elevated alkaline phosphatase levels and an increased proportion of blood eosinophils were more prevalent in patients with the homozygous CC genotype of the rs2069705 IFNG polymorphism. We found no association between the rs12979860 IL28b polymorphism and manifestations of O. felineus invasion.

Conclusion. From our point of view, patients with opisthorchiasis who have the rs2069705 IFNG polymorphism should be identified during dispensary observation as a risk group to prevent the development of complications of parasitic invasion, which include liver fibrosis and hepatocellular carcinoma.

1. Tsukanov VV, Vasyutin AV, Tonkikh JL. Parasites of the liver: A global problem? World J Gastroenterol. 2024;30(30):3554–3559. https://doi.org/10.3748/wjg.v30.i30.3554.

2. Peters L, Burkert S, Grüner B. Parasites of the liver – epidemiology, diagnosis and clinical management in the European context. J Hepatol. 2021;75(1):202–218. https://doi.org/10.1016/j.jhep.2021.02.015.

3. Busabong W, Woradet S, Songserm N. Impact of self-efficacy-based health education programs on behavior modification for Opisthorchis viverrini and cholangiocarcinoma prevention in Thailand: A systematic review and meta-analysis. Parasites Hosts Dis. 2025;63(1):1–11. https://doi.org/10.3347/PHD.24074.

4. Fedorova OS, Fedotova MM, Sokolova TS, Golovach EA, Kovshirina YV, Ageeva TS et al. Opisthorchis felineus infection prevalence in Western Siberia: A review of Russian literature. Acta Trop. 2018;178:196–204. https://doi.org/10.1016/j.actatropica.2017.11.018.

5. Tsukanov VV, Gorchilova EG, Kolenchukova OA, Gvozdev II, Savchenko AA, Kasparov EV et al. Functional activity of blood neutrophilic granulocytes in patients with opisthorchiasis, depending on the severity of liver fibrosis. Terapevticheskii Arkhiv. 2021;93(11):1271–1277. (In Russ.) https://doi.org/10.26442/00403660.2021.11.201165.

6. Vasyutin AV, Tsukanov VV, Veselova NE, Gorchilova EG, Tonkikh JuL, Savchenko AA, Borisov AG. Association of neutropenia and decreased neutrophil function with liver fibrosis in patients with Opisthorchis felineus invasion. Meditsinskiy Sovet. 2024;18(15):62–69. (In Russ.) https://doi.org/10.21518/ms2024-339.

7. Tsukanov VV, Veselova NE, Savchenko AA, Kolenchukova OA, Gvozdev II, Vasyutin AV et al. Functional activity of blood eosinophils in patients with Opisthorchis felineus invasion. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2023;33(6):26–35. (In Russ.) https://doi.org/10.22416/1382-4376-2023-33-6-26-35.

8. Karbysheva N, Nikonorova M, Matros O, Kiushkina I, Nemilostiva E, Choroshilova I et al. Clinical polymorphism in patients with Opisthorchis felineus infection in the Western Siberia. IDCases. 2021;24:e01064. https://doi.org/10.1016/j.idcr.2021.e01064.

9. Huang YL, Zhang KY, Sun YL, Qian MB, Wang Z. The risk of hepatobiliary complications in Clonorchis and Opisthorchis infection: A systematic review and meta-analysis. Acta Trop. 2024;260:107457. https://doi.org/10.1016/j.actatropica.2024.107457.

10. Veselova NE, Tsukanov VV, Savchenko AA, Vasyutin AV, Tonkikh JuL, Fursova YE. Association of clinical manifestations of Opisthorchis felineus invasion with elevated FIB-4 index levels. Meditsinskiy Sovet. 2025;19(8):120–125. (In Russ.) https://doi.org/10.21518/ms2025-216.

11. Zhang Z, Wang J, Li H, Niu Q, Tao Y, Zhao X et al. The role of the interleukin family in liver fibrosis. Front Immunol. 2025;16:1497095. https://doi.org/10.3389/fimmu.2025.1497095.

12. Bozward AG, Davies SP, Morris SM, Kayani K, Oo YH. Cellular interactions in selfdirected immune-mediated liver diseases. J Hepatol. 2025;82(6):1110–1124. https://doi.org/10.1016/j.jhep.2025.01.002.

13. Gao Y, Yin Y, Xie P, Zhang D, Li H, Qi X. Interferon in Liver Diseases: Recent Advances. Adv Ther. 2025;42(9):4210–4223. https://doi.org/10.1007/s12325-025-03291-8.

14. Boehmer D, Ghosh S, Jena KK, Akusjärvi SS, Zanoni I. Molecular, Cellular, Tissue, and Organismal Functions of Type III Interferons. Annu Rev Immunol. 2026;44(1):121–147. https://doi.org/10.1146/annurev-immunol-083024-032807.

15. Surapaitoon A, Suttiprapa S, Mairiang E, Khuntikeo N, Pairojkul C, Bethony J et al. Subsets of Inflammatory Cytokine Gene Polymorphisms are Associated with Risk of Carcinogenic Liver Fluke Opisthorchis viverrini-Associated Advanced Periductal Fibrosis and Cholangiocarcinoma. Korean J Parasitol. 2017;55(3):295–304. https://doi.org/10.3347/kjp.2017.55.3.295.

16. Sitthirak S, Wangwiwatsin A, Jusakul A, Namwat N, Klanrit P, Dokduang H et al. Whole exome sequencing of multi-regions reveals tumor heterogeneity in Opisthorchis viverrini-associated cholangiocarcinoma. Sci Rep. 2025;15(1):10886. https://doi.org/10.1038/s41598-025-95142-3.

17. Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349(9055):825–832. https://doi.org/10.1016/s0140-6736(96)07642-8.

18. Li L, Li X, Zhang F. The pivotal role of cytokines in liver disease pathogenesis and therapeutic potential. Front Immunol. 2025;16:1694582. https://doi.org/10.3389/fimmu.2025.1694582.

19. Balagopal A, Thomas DL, Thio CL. IL28B and the control of hepatitis C virus infection. Gastroenterology. 2010;139(6):1865–1876. https://doi.org/10.1053/j.gastro.2010.10.004.

20. Miri HH, Fazeli P, Ali-Hassanzadeh M, Bemani P, Kabelitz D, Kalantar K. Correlation between IL-28 polymorphism and spontaneous clearance in HCV patients: systematic review and meta-analysis. Arch Virol. 2021;166(9):2469–2478. https://doi.org/10.1007/s00705-021-05141-8.

21. Boglione L, Cusato J, Cariti G, Di Perri G, D’Avolio A. Role of IL28B genotype in the liver stiffness increase in untreated patients with chronic hepatitis C. Infect Genet Evol. 2017;53:195–198. https://doi.org/10.1016/j.meegid.2017.05.026.

22. Khalil FO, Alsebaey A, Kasemy ZA, Abdelmageed SM, Bedair HM, Abdelsattar S. IL28B, TLR7 SNPs, and cytomegalovirus infection are risk factors for advanced liver disease in chronic hepatitis C patients. Expert Rev Anti Infect Ther. 2022;20(1):121–129. https://doi.org/10.1080/14787210.2021.1935239.

23. Ataherian MR, Hafezi N, Ferdosi-Shahandashti E, Abdinia FS. IFN-γ Approaches in Tumor Suppression, Its Challenges, and Future Directions: A Review of Recent Advances. J Interferon Cytokine Res. 2025;45(5):164–173. https://doi.org/10.1089/jir.2024.0259.

24. Cui J, Zhang Y, Yang L. IFN-gamma in the tumor microenvironment: dual roles in cancer progression and therapy. EXCLI J. 2025;24:1352–1371. https://doi.org/10.17179/excli2025-8617.

25. Suri P, Badalov A, Ruggiu M. Alternative Splicing as a Modulator of the Interferon-Gamma Pathway. Cancers. 2025;17(4):594. https://doi.org/10.3390/cancers17040594.

26. Rafiq K, Khan S, Khan MB, Yaqoob M, Adnan M. Genetic Influence of IFN-γ gene Polymorphisms on Hepatitis C Progression and Recovery. J Virol Methods. 2026;342:115337. https://doi.org/10.1016/j.jviromet.2026.115337.