BLOOD PLASMA СYTOKINE LEVELS IN PATIENTS WITH CHRONIC VIRAL HEPATITIS B STAGE-DEPENDENT LIVER FIBROSIS



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Abstract

Abstract

Introduction. Hepatitis B is an infectious inflammatory liver disease resulting from hepatitis B virus infection. According to the WHO estimates, 254 million people with chronic hepatitis B (CHB) were recorded worldwide in 2022. CHB is accompanied by developing liver fibrosis, which leads to impaired liver function. The progression of liver fibrosis involves multilayered cellular interactions between hepatic stellate cells, resident macrophages, and specialized immune cells. this cell interplay is regulated by humoral factors, among which cytokines play a key role. Due to this, the analysis of peripheral blood cytokines in CHB patients allows assessment of immune process activity in the liver, fibrosis progression intensity, and therapeutic effectiveness. The aim of our work was to evaluate blood plasma cytokine spectrum in CHB patients related to liver fibrosis staging. Materials and methods. The study included 53 patients diagnosed with chronic viral hepatitis B, subdivided into three groups based on liver fibrosis stage. Blood plasma samples were collected from all study subjects. Concentration for 42 cytokines was assessed by xMAP multiplexing technology. The results underwent statistical processing using nonparametric statistical methods. Results. Compared to apparently healthy group, CHB patients showed: significantly elevated concentrations for IL-6, IL-27, CCL11/Eotaxin, CXCL9/MIG, CXCL-10/IP-10, M-CSF; significantly decreased levels for IL-2, IL-4, IL-12(p70), IL-13, IL-17A, IFN2α, sCD40L, CCL3/MIP-1α, CCL7/MCP-3, CXCL1/GROα, CXCL8/IL-8, CX3CL1/Fractalkine, EGF, PDGF-AA, PDGF-AB/BB, VEGF-A. Based on different liver fibrosis stages, significant differences in cytokine levels were found between patient groups for: IL-6, IL-10, IL-12(p70), IL-27, sCD40L, CXCL9/MIG, CXCL-10/IP-10, M-CSF, PDGF-AA, PDGF-AB/BB. Correlation analysis revealed a positive relationship between liver fibrosis severity and levels for IL-6, IL-27, TNFα, CXCL8/IL-8, CXCL9/MIG, CXCL10/IP-10, and M-CSF, and a negative relationship between the severity of liver fibrosis and levels for IL-12(p70), IFN2α, sCD40L, CX3CL1/Fractalkine, EGF, PDGF-AA and PDGF-AB/BB. Thus, blood plasma cytokine spectrum in CHB patients was evaluated, identifying factors involved in CHB immunopathogenesis, including those playing a significant role for developing liver fibrosis.

About the authors

Oleg K. Batsunov

Saint Petersburg Pasteur Institute, St. Petersburg, Russian Federation;
Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation

Email: batsunov@gmail.com
ORCID iD: 0000-0002-0954-6662
SPIN-code: 3440-4022
Scopus Author ID: 57206671620
ResearcherId: ELV-2518-2022

junior researcher, laboratory of Molecular immunology; assistant of the department, department of Immunology 

Россия, St. Petersburg; St. Petersburg

Natalia A. Arsentieva

Saint Petersburg Pasteur Institute, St. Petersburg, Russian Federation;
Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation

Email: arsentieva_n.a@bk.ru
ORCID iD: 0000-0003-2490-308X
SPIN-code: 7300-0182

PhD (Biology), Senior Researcher, Laboratory of Molecular Immunology; Assistant Professor, Department of Immunology

Россия, St. Petersburg; St. Petersburg

Natalia E. Liubimova

Saint Petersburg Pasteur Institute, St. Petersburg, Russian Federation

Email: natelu@mail.ru
ORCID iD: 0009-0003-7092-6773
SPIN-code: 9981-9188

PhD (Biology), Researcher, Laboratory of Molecular Immunology

Россия, St. Petersburg

Duc Trong Duong

Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation

Email: ductrong@yandex.ru

infectious disease doctor of the Department of epidemiology

Россия, St. Petersburg

Valentina V. Basina

Saint Petersburg State Pediatric Medical University, St. Petersburg, Russian Federation

Email: v.basina@mail.ru
ORCID iD: 0000-0001-8095-1428

PhD (Medicine), Assistant of the Department of Infectious Diseases Adults and Epidemiology

Россия, Saint-Petersburg

Elena V. Esaulenko

Saint Petersburg Pasteur Institute, St. Petersburg, Russian Federation;
Saint Petersburg State Pediatric Medical University, St. Petersburg, Russian Federation

Email: eve-gpmu@mail.ru

PhD, MD (Medicine), Professor, Head of the Viral Hepatitis Laboratory

Россия, 14, Mira str., St. Petersburg, 197101

Areg A. Totolian

Saint Petersburg Pasteur Institute, St. Petersburg, Russian Federation;
Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation

Author for correspondence.
Email: totolian@pasteurorg.ru
ORCID iD: 0000-0003-4571-8799
SPIN-code: 3369-8560

RAS Full Member, PhD, MD (Medicine), Professor, Director; Head of the Department of Immunology

Россия, St. Petersburg; St. Petersburg

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