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

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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.

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作者简介

Andrey Savchenko

Krasnoyarsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences

编辑信件的主要联系方式.
Email: aasavchenko@yandex.ru
ORCID iD: 0000-0001-5829-672X

Research Institute of Medical Problems of the North, Professor, MD, Head, Laboratory of Cellular and Molecular Physiology and Pathology

俄罗斯联邦, Krasnoyarsk

Elena Tikhonova

Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Email: tihonovaep@mail.ru
ORCID iD: 0000-0001-6466-9609

MD, Head, Department of Infectious Diseases and Epidemiology with the Course of Postgraduate Education, Professor

俄罗斯联邦, Krasnoyarsk

Anna Anisimova

N.S. Karpovich Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medicine

Email: tada1@mail.ru

Physician, Infectious Diseases Department

俄罗斯联邦, Krasnoyarsk

Igor Kudryavtsev

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

Email: igorek1981@yandex.ru
ORCID iD: 0000-0001-5637-2143

Cand. Biol. Sci., Head, Cellular Immunology Laboratory, Immunology Department, Associate Professor, Immunology Department

俄罗斯联邦, Saint Petersburg; Saint Petersburg

Elena Anisimova

Krasnoyarsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences

Email: foi-543@mail.ru
ORCID iD: 0000-0002-6120-159X

Research Institute of Medical Problems of the North, Cand. Med. Sci., Senior Researcher, Cellular and Molecular Physiology and Pathology Laboratory

俄罗斯联邦, Krasnoyarsk

Aleksandr Borisov

Krasnoyarsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences

Email: 2410454@mail.ru
ORCID iD: 0000-0002-9026-2615

Research Institute of Medical Problems of the North, Cand. Med. Sci., Leading Researcher, Laboratory of Cellular and Molecular Physiology and Pathology

俄罗斯联邦, Krasnoyarsk

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