Relationship between NKT cell phenotype and liver fibrosis degree in patients with chronic hepatitis C before and after treatment


DOI: https://dx.doi.org/10.18565/epidem.2024.14.4.60-9

Savchenko A.A., Tikhonova E.P., Anisimova A.A., Kudryavtsev I.V., Anisimova E.N., Borisov A.G.

1) Krasnoyarsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North, Krasnoyarsk, Russia; 2) Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia; 3) N.S. Karpovich Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medicine, Krasnoyarsk, Russia; 4) Research Institute of Experimental Medicine, Saint Petersburg, Russia; 5) Pavlov First Saint Petersburg State Medical University, Sant Petersburg, Russia
Objective. Determination of the features of the NKT cell phenotype in patients with chronic hepatitis C (CHC) with varying fibrosis degrees before and after treatment with direct-acting antiviral drugs (DAAs).
Materials and methods. A total of 112 patients with CHC aged 44.2 ± 7.4 years were examined. The diagnosis was confirmed by PCR-RNA of the hepatitis C virus (HCV). To diagnose liver fibrosis, the shear wave transient elastometry method was used. Patients with CHC were treated with DAAs, Sofosbuvir 400 mg/day and Velpatasvir 100 mg/day, for 12 weeks. Depending on the liver fibrosis degree before the start of DAA treatment, patients with CHC were divided into 3 groups: with fibrosis F0-F1, with fibrosis F2 and with fibrosis F3–F4. All patients were examined before and after DAA treatment. As a control, 23 healthy people of the same age range were examined. The study of the phenotypic composition of NKT cells was performed by flow cytometry.
Results. The features of the NKT cell phenotype which characterize the functional activity of this fraction of lymphocytes were established. Changes in the NKT cell phenotype in patients with CHC depended on the examination period (before or after DAA treatment). Before treatment, against the background of a high viral load and ALT activity in the blood, the NKT cell phenotype slightly depended on the fibrosis degree and was characterized by a high level of expression of the CD57 receptor on the membranes of total NKT cells, as well as lymphocytes of this fraction expressing CD8, CD62L and CD94 markers. After treatment, patients achieved complete HCV clearance. Against this background, the features of the NKT cell phenotype began to depend more significantly on the fibrosis degree, while characterizing the preservation of inflammatory imprinting in the immune system. The most significant changes in the NKT cell phenotype were found in patients with fibrosis F3–F4, which were expressed in a reduced number of CD62L+NKT cells, the maximum level of CD73+NKT cells, and the preservation of a high level of CD57 expression on the surface of CD8+ and CD94+NKT cells.
Conclusion. It is necessary to develop a differentiated approach to the treatment of liver fibrosis and methods for predicting the development of hepatocellular carcinoma in patients with a high degree of fibrosis after successful antiviral therapy.
Keywords: NKT cells, degree of fibrosis, subpopulations, chronic hepatitis C, phenotype, treatment
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About the Autors

Professor Andrey A. Savchenko, MD, Head, Laboratory of Cellular and Molecular Physiology and Pathology, Krasnoyarsk Scientific Center, Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North, Krasnoyarsk, Russia; aasavchenko@yandex.ru; https://orcid.org/0000-0001-5829-672Х
Professor Elena P. Tikhonova, MD, Head, Department of Infectious Diseases and Epidemiology with the Course of Postgraduate Education, Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, Russia; tihonovaep@mail.ru; https://orcid.org/0000-0001-6466-9609
Anna A. Anisimova, Physician, Infectious Diseases Department, N.S. Karpovich Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medicine, Krasnoyarsk, Russia; tada1@mail.ru.
Igor V. Kudryavtsev, Cand. Biol. Sci., Head, Cellular Immunology Laboratory, Immunology Department, Institute of Experimental Medicine; Associate Professor, Immunology Department, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia; igorek1981@yandex.ru,
Elena N. Anisimova, Cand. Med. Sci., Senior Researcher, Cellular and Molecular Physiology and Pathology Laboratory, Krasnoyarsk Scientific Center, Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North, Krasnoyarsk, Russia; foi-543@mail.ru; https://orcid.org/0000-0002-6120-159X
Aleksandr G. Borisov, Cand. Med. Sci., Leading Researcher, Laboratory of Cellular and Molecular Physiology and Pathology, Krasnoyarsk Scientific Center, Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North, Krasnoyarsk, Russia; 2410454@mail.ru; https://orcid.org/0000-0002-9026-2615


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