Association of neutropenia and decreased neutrophil function with liver fibrosis in patients with Opisthorchis felineus invasion
A. V. Vasyutin,
V. V. Tsukanov,
N. E. Veselova,
E. G. Gorchilova,
J. L. Tonkikh,
A. A. Savchenko,
A. G. Borisov https://doi.org/10.21518/ms2024-339
Abstract
Introduction. Neutrophils are important participants in the innate immune response, are the first to react to a pathogenic factor and quickly develop non-specific reactions. At the same time, there are no studies on the functional activity of neutrophils in patients with Opisthorchis felineus (O. felineus) invasion.
Aim. To study the clinical and laboratory manifestations of opisthorchiasis depending on the leukocyte indicators of the complete blood count.
Materials and methods. A total of 328 patients with O. felineus invasion (120 men and 208 women) and 51 practically healthy patients (28 men and 23 women) were examined. Opisthorchiasis was diagnosed using coproovoscopy and microscopy of duodenal contents. All patients with O. felineus invasion underwent complete and biochemical blood tests. Liver elastometry using Aixplorer (France) or Siemens Acuson S2000 (Germany) with determination of the liver fibrosis degree according to METAVIR, and blood neutrophils functional activity study were performed in 103 patients with chronic opisthorchiasis (58 men and 45 women).
Results. A tendency was found to increase the proportion of leukopenia by 3.5 times (p = 0.12) and neutropenia by 1.9 times (p = 0.15) in patients with liver fibrosis F2-F3 according to METAVIR compared to individuals with liver fibrosis F0 according to METAVIR. The absolute neutrophil content in patients with O. felineus invasion and liver fibrosis F2-F3 according to METAVIR was decreased in comparison with individuals with liver fibrosis F0 according to METAVIR (2.24 × 109/l versus 3.06 × 109/l, p = 0.04). A decrease in the functional activity of neutrophils in the blood was also registered in patients with liver fibrosis F2-F3 according to METAVIR in comparison with individuals with F0 according to METAVIR.
Conclusion. A decrease in the number and functional activity of neutrophils in the blood may be markers of an increased risk of liver fibrosis in patients with opisthorchiasis. It is advisable to study the possibilities of immunomodulatory drugs on the course of O. felineus invasion.
About the Authors
A. V. Vasyutin
Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences of Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Alexander V. Vasyutin, Cand. Sci. (Med.), Senior Researcher of the Clinical Department of the Clinical Department of the Digestive System Pathology of Adults and Children
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
V. V. Tsukanov
Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences of Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Vladislav V. Tsukanov, Dr. Sci. (Med.), Professor, Head of the Clinical Department of the Digestive System Pathology of Adults and Children
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
N. E. Veselova
Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences of Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Natalia E. Veselova, Junior Researcher of the Clinical Department of the Clinical Department of the Digestive System Pathology of Adults and Children
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
E. G. Gorchilova
Clinical Hospital RZD-Medicine of Krasnoyarsk City
Russian Federation
Russian Federation
Ekaterina G. Gorchilova, Gastroenterologist of the Gastroenterological Department
47, Lomonosov St., Krasnoyarsk, 660058
J. L. Tonkikh
Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences of Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Julia L. Tonkikh, Cand. Sci. (Med.), Leading Researcher of the Clinical Department of the Clinical Department of the Digestive System Pathology of Adults and Children
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
A. A. Savchenko
Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences of Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Andrey A. Savchenko, Dr. Sci. (Med.), Professor, Head of the Laboratory of Cellular and Molecular Physiology and Pathology
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
A. G. Borisov
Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences of Scientific Research Institute of Medical Problems of the North
Russian Federation
Russian Federation
Alexander G. Borisov, Cand. Sci. (Med.), Leading Researcher of the Laboratory of Cellular and Molecular Physiology and Pathology
3g, Partizan Zheleznyak St., Krasnoyarsk, 660022
References
1. 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.
2. Plotnikova EY, Baranova EN. Plotnikova E.Yu., Baranova Е.N. Problems of treatment of opisthorchiasis. RMJ. Medical Review. 2018;2(3):53–56. (In Russ.) Available at: https://www.rmj.ru/articles/gastroenterologiya/Problemy_lecheniyaopistorhoznoy_invazii.
3. Tsukanov VV, Tonkikh YuL, Gilyuk AV, Vasyutin AV, Kolenchukova OA, Rzhavicheva OS et al. Opisthorchiasis: Diagnostics, Clinical Manifestations, and Management. Doctor.Ru. 2019;8(163):49–53. (In Russ.) https://doi.org/10.31550/1727-2378-2019-163-8-49-53.
4. 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.
5. Kovner AV, Pakharukova MY, Maksimova GA, Mordvinov VA. Characteristics of liver fibrosis associated with chronic Opisthorchis felineus infection in Syrian hamsters and humans. Exp Mol Pathol. 2019;110:104274. https://doi.org/10.1016/j.yexmp.2019.104274.
6. Thuwajit C, Thuwajit P, Uchida K, Daorueang D, Kaewkes S, Wongkham S, Miwa M. Gene expression profiling defined pathways correlated with fibroblast cell proliferation induced by Opisthorchis viverrini excretory/ secretory product. World J Gastroenterol. 2006;12(22):3585–3592. https://doi.org/10.3748/wjg.v12.i22.3585.
7. Tan S, Machrumnizar M. Fish and Food-Fatale: Food-borne Trematode Opisthorchis viverrini and Cholangiocarcinoma. Helminthologia. 2023;60(4):287–299. https://doi.org/10.2478/helm-2023-0036.
8. Sripa B, Brindley PJ, Mulvenna J, Laha T, Smout MJ, Mairiang E et al. The tumorigenic liver fluke Opisthorchis viverrini-multiple pathways to cancer. Trends Parasitol. 2012;28(10):395–407. https://doi.org/10.1016/j.pt.2012.07.006.
9. Zhang CY, Liu S, Yang M. Treatment of liver fibrosis: Past, current, and future. World J Hepatol. 2023;15(6):755–774. https://doi.org/10.4254/wjh.v15.i6.755.
10. Pakharukova MY, Lishai EA, Zaparina O, Baginskaya NV, Hong SJ, Sripa B, Mordvinov VA. Opisthorchis viverrini, Clonorchis sinensis and Opisthorchis felineus liver flukes affect mammalian host microbiome in a speciesspecific manner. PLoS Negl Trop Dis. 2023;17(2):e0011111. https://doi.org/10.1371/journal.pntd.0011111.
11. Kovner AV, Kapushchak YK, Zaparina O, Mordvinov VA, Pakharukova MY. Hepatic vascular changes associated with Opisthorchis felineus infection in Syrian hamsters and humans. Acta Trop. 2024;250:107100. https://doi.org/10.1016/j.actatropica.2023.107100.
12. Hata T, Hiromichi I. Biliary Parasitic Diseases Associated with Hepatobiliary Carcinoma. Visc Med. 2023;39(3-4):71–75. https://doi.org/10.1159/000531599.
13. Sivanand A, Talati D, Kalariya Y, Patel P, Gandhi SK. Associations of Liver Fluke Infection and Cholangiocarcinoma: A Scoping Review. Cureus. 2023;15(10):e46400. https://doi.org/10.7759/cureus.46400.
14. Qian M-B, Keiser J, Utzinger J, Zhou X-N. Clonorchiasis and opisthorchiasis: epidemiology, transmission, clinical features, morbidity, diagnosis, treatment, and control. Clin Microbiol Rev. 2024;37(1):e0000923. https://doi.org/10.1128/cmr.00009-23.
15. Reis ES, Mastellos DC, Hajishengallis G, Lambris JD. New insights into the immune functions of complement. Nat Rev Immunol. 2019;19(8):503–516. https://doi.org/10.1038/s41577-019-0168-x.
16. Zhang H, He F, Li P, Hardwidge PR, Li N, Peng Y. The Role of Innate Immunity in Pulmonary Infections. Biomed Res Int. 2021;2021:6646071. https://doi.org/10.1155/2021/6646071.
17. Orsini EM, Perelas A, Southern BD, Grove LM, Olman MA, Scheraga RG. Stretching the Function of Innate Immune Cells. Front Immunol. 2021;12:767319. https://doi.org/10.3389/fimmu.2021.767319.
18. Hu S, Liu X, Gao Y, Zhou R, Wei M, Dong J et al. Hepatitis B Virus Inhibits Neutrophil Extracellular Trap Release by Modulating Reactive Oxygen Species Production and Autophagy. J Immunol. 2019;202(3):805–815. https://doi.org/10.4049/jimmunol.1800871.
19. Lacy BE, Mearin F, Chang L, Chey WD, Lembo AJ, Simren M et al. Bowel Disorders. Gastroenterology. 2016;150(6):1393–1407. https://doi.org/10.1053/j.gastro.2016.02.031.
20. Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J et al. Gastroduodenal Disorders. Gastroenterology. 2016;150(6):1380–1392. https://doi.org/10.1053/j.gastro.2016.02.011.
21. Liew PX, Kubes P. The Neutrophil’s Role During Health and Disease. Physiol Rev. 2019;99(2):1223–1248. https://doi.org/10.1152/physrev.00012.2018.
22. Hammerich L, Tacke F. Hepatic inflammatory responses in liver fibrosis. Nat Rev Gastroenterol Hepatol. 2023;20(10):633–646. https://doi.org/10.1038/s41575-023-00807-x.
23. Liu K, Wang FS, Xu R. Neutrophils in liver diseases: pathogenesis and therapeutic targets. Cell Mol Immunol. 2021;18(1):38–44. https://doi.org/10.1038/s41423-020-00560-0.
24. Moreau R, Périanin A, Arroyo V. Review of Defective NADPH Oxidase Activity and Myeloperoxidase Release in Neutrophils From Patients With Cirrhosis. Front Immunol. 2019;10:1044. https://doi.org/10.3389/fimmu.2019.01044.
25. Taylor NJ, Manakkat Vijay GK, Abeles RD, Auzinger G, Bernal W et al. The severity of circulating neutrophil dysfunction in patients with cirrhosis is associated with 90-day and 1-year mortality. Aliment Pharmacol Ther. 2014;40(6):705–715. https://doi.org/10.1111/apt.12886.
26. Boussif A, Rolas L, Weiss E, Bouriche H, Moreau R, Périanin A. Impaired intracellular signaling, myeloperoxidase release and bactericidal activity of neutrophils from patients with alcoholic cirrhosis. J Hepatol. 2016;64(5):1041–1048. https://doi.org/10.1016/j.jhep.2015.12.005.
27. Agraz-Cibrian JM, Segura-Ortega JE, Delgado-Rizo V, Fafutis-Morris M. Alterations in neutrophil extracellular traps is associated with the degree of decompensation of liver cirrhosis. J Infect Dev Ctries. 2016;10(5):512–517. https://doi.org/10.3855/jidc.7165.
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For citations:
Vasyutin AV, Tsukanov VV, Veselova NE, Gorchilova EG, Tonkikh JL, Savchenko AA, Borisov AG. Association of neutropenia and decreased neutrophil function with liver fibrosis in patients with Opisthorchis felineus invasion. Meditsinskiy sovet = Medical Council. 2024;(15):62–69. (In Russ.) https://doi.org/10.21518/ms2024-339
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