A relation between T cell phenotypic profile and virus genotype in patients with chronic viral hepatitis (before and after treatment with direct antiviral agents)

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Abstract

The aim of the study was to investigate the phenotype of effector T lymphocytes in patients with chronic viral hepatitis C (CVHC) before and after of treatment with direct antiviral drugs depending on the genotype of the virus. 50 patients with CVHC without signs of liver cirrhosis were examined. The diagnosis was made on the basis of epidemiological and clinical laboratory data as recommended by the European Association for the Study of the Liver when specific serological markers of CHCV and RNA of hepatitis C virus (HCV) were detected (EASL, 2016). The determination of HCV RNA was carried out by the method of quantitative polymerase chain reaction in real time. The degree of liver fibrosis in patients with CVHC was assessed using ultrasound elastography. Patients were treated for 3 months with direct antiviral drugs according to the recommendations of the European Association for the Study of the Liver (2016). The control group included 46 practically healthy individuals with severe chronic diseases of various organs and systems excluded during a routine examination, no health complaints, having normal clinical and biochemical blood tests in the absence of markers for viral hepatitis B and C, antibodies to opisthorchis and denying history of alcohol abuse. The study of the subpopulation composition of helper and cytotoxic T lymphocytes was carried out by direct immunofluorescence of whole peripheral blood. We obtained a 100% sustained virological response in patients with 1, 2 and genotypes of CHCV without signs of liver cirrhosis when using therapy with Sofosbuvir (400 mg) and Daclatasvir (60 mg) for 12 weeks. It was found that in CVHC patients were found characteristic features in the phenotypic composition of effector T lymphocytes before and after treatment with direct antiviral drugs in depending on the genotype of HCV. Patients with HCV genotypes 1 and 3 had an increase in the content of terminal differentiated effector (TEMRA) T helpers and effector memory (EM). Only patients with HCV genotype 2 had a decrease in the level of EM T-helper cells in the blood. A decrease in the relative number of T helpers of central memory (СM) was independent of the HCV genotype. The level of effector subpopulations of cytotoxic T lymphocytes in patients with CVHC was consistent with or exceeded control levels in depending on the genotype of HCV. The level of all investigated subpopulations of effector cytotoxic T lymphocytes in patients with HCV genotype 1 was equal to the control values. The number of naïve cytotoxic T cells and CM in peripheral blood in patients with HCV genotype 2 was increased. The content of naïve cytotoxic T lymphocytes, CM and TEMRA in patients with genotype 3 HCV in the blood was increased. The highest viral load was detected in patients with CVHC with genotype 1 HCV. Liver fibrosis was most pronounced in patients with CVHC infection with HCV genotypes 2 and 3. After 3 months of treatment with direct antiviral drugs the patients with CVHC had a reduced content of CM T helpers regardless of the HCV genotype. In addition, patients with HCV genotypes 1 and 3 had a decrease in the number of naïve T helpers and patients with HCV genotypes 2 and 3 had a normalization of the content of naïve cytotoxic T lymphocytes.

About the authors

A. A. Savchenko

Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North

Email: aasavchenko@yandex.ru

PhD, MD (Medicine), Professor, Head of the Laboratory of Cellular-Molecular Physiology and Pathology, Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North.

Krasnoyarsk.

Russian Federation

V. V. Tsukanov

Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North

Email: aasavchenko@yandex.ru

PhD, MD (Medicine), Professor, Head of the Clinical Department of Digestive System Pathology, Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North.

Krasnoyarsk.

Russian Federation

I. V. Kudryavtsev

Institute of Experimental Medicine; Pavlov First Saint Petersburg State Medical University

Author for correspondence.
Email: igorek1981@yandex.ru

Igor V. Kudryavtsev - PhD (Biology), Head of the Cell Immunology Laboratory, Department of Immunology, Institute of Experimental Medicine; Assistant Professor, Department of Immunology, Pavlov First Saint Petersburg State Medical University.

197376, St. Petersburg, Academician Pavlov str., 12.

Phone: +7 812 234-29-29

Russian Federation

J. L. Tonkih

Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North

Email: aasavchenko@yandex.ru

PhD (Medicine), Leading Researcher, Clinical Department of Digestive System Pathology, Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North.

Krasnoyarsk.

Russian Federation

V. D. Belenjuk

Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North

Email: dyh.88@mail.ru

Junior Researcher, Laboratory of Cellular-Molecular Physiology and Pathology, Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North.

Krasnoyarsk.

Russian Federation

M. A. Cherepnin

Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North

Email: fake@neicon.ru

Junior Researcher, Clinical Department of Digestive System Pathology, Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North.

Krasnoyarsk.

Russian Federation

A. A. Anisimova

Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North

Email: fake@neicon.ru

Junior Researcher, Clinical Department of Digestive System Pathology, Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North.

Krasnoyarsk.

Russian Federation

A. G. Borisov

Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North

Email: 2410454@mail.ru

PhD (Medicine), Leading Researcher, Laboratory of Cellular-Molecular Physiology and Pathology, Krasnoyarsk Research Center of the Siberian Branch of the Russian Academy of Sciences, Research Institute of Medical Problems of the North.

Krasnoyarsk.

Russian Federation

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Copyright (c) 2021 Savchenko A.A., Tsukanov V.V., Kudryavtsev I.V., Tonkih J.L., Belenjuk V.D., Cherepnin M.A., Anisimova A.A., Borisov A.G.

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