FIBROGENESIS MARKERS AND CYTOKINE PROFILE IN CHILDREN WITH AUTOIMMUNE HEPATITIS DEPENDING ON THERAPY EFFECTIVENESS



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Abstract

Autoimmune hepatitis (AHH) in children is characterized by high inflammatory activity and the risk of rapid progression of liver fibrosis, however, the dynamics of fibrogenesis markers and cytokine profile during therapy have not been sufficiently studied. The aim of the study was to evaluate changes in fibrosis markers and cytokine profile in children with AH depending on the effectiveness of therapy and to determine their prognostic significance.

The study included 48 children with AH (Me age 11.6 [7.9;16.0] years). The stage of liver fibrosis was assessed before the start of glucocorticosteroid therapy and after 6 months of treatment according to the METAVIR scale (F0-F4). Depending on the dynamics of fibrosis, patients were divided into groups with a good effect of therapy, who had regression of fibrosis (HE, n=22) and with insufficient effect of therapy, all patients in this group had stage F4 fibrosis before and after therapy (HE, n=26). The levels of CTGF, VEGF, TGF-β1, PDGF-BB, hyaluronic acid (HA) in blood serum were determined by ELISA. 14 cytokines using were determined by a multiplex analysis of a ProcartaPlex reagent kit (Invitrogen, USA) on a QuattroPlex Lab multiplex analyzer (Ivok, Russia).

In patients with CE, there was a significant decrease in HA levels (p<0.001), an increase in TGF-β1 (p<0.001), and a decrease in IL-10 (p=0.006). In the NE group, signs of immuno-inflammatory activity persisted, accompanied by an increase in IL-1a and a higher level of IL-21 after 6 months of therapy (p<0.001). PDGF-BB before the start of therapy (AUC=0.876), IL-21 after 6 months of treatment (AUC=0.867), TGF-β1 (AUC=0.825) and HA (AUC=0.762) had the highest prognostic informative value. The data obtained show that in children with AH, the processes of liver fibrosis have different dynamics and are associated not only with classical markers of extracellular matrix formation, but also with cytokine profile features.

A comprehensive assessment of fibrogenesis markers and cytokine profile can be considered as a promising noninvasive approach to predicting the dynamics of fibrosis and the effectiveness of therapy.

About the authors

Olga V. Kurbatova

National Medical Research Center for Children’s Health

Email: putintseva@mail.ru
ORCID iD: 0000-0002-9213-5281

Ph.D. (Medicine), Senior Researcher, Head of laboratory of Experimental Immunology and Virology

Russian Federation, 2 Lomonosovsky Ave, Bldg 1Moscow 119991

Goar B. Movsisyan

National Medical Research Center for Children’s Health

Email: movsisyan@nczd.ru
ORCID iD: 0000-0003-2881-4703

Senior Researcher of the Laboratory of Rare Hereditary Diseases, Gastroenterologist of the Gastroenterology Department with the Hepatological Group

Russian Federation, 2/1 Lomonosovsky Ave, Moscow, 119991

Tatiana V. Radygina

National Medical Research Center for Children’s Health

Email: tvradigina@mail.ru
ORCID iD: 0000-0003-4704-6885

Ph.D. (Medicine), Senior  Research  Associate, Laboratory of Experimental Immunology and Virology

Russian Federation, 2/1, Lomonosovskiy Pr-t, Moscow, 119991

A. P. Fisenko

National Medical Research Center for Children’s Health

Email: fisenko@nczd.ru
ORCID iD: 0000-0001-8586-7946

PhD, MD (Medicine), Professor, Head, National Medical Research Center for Children’s Health

Russian Federation, Moscow

Matvey V. Konyashin

National Medical Research Center for Children’s Health

Email: matele99@mail.ru

Clinical Laboratory Doctor, Laboratory of Experimental Immunology and Virology

Russian Federation, Moscow

Anastasia A. Zhuzhula

National Medical Research Center for Children’s Health

Email: Anas-zh@inbox.ru
ORCID iD: 0000-0002-6292-7229
SPIN-code: 8783-9571
Scopus Author ID: 57226395657
ResearcherId: AGU-5991-2022

Junior Researcher at the Laboratory of Experimental Immunology and Virology

Russian Federation, 2 Lomonosovsky Ave, Bldg 1Moscow 119991

Marina A. Snovskaya

National Medical Research Center for Children’s Health

Email: snows@inbox.ru
ORCID iD: 0000-0002-5263-6743

PhD (Medicine), Leading Researcher, Laboratory of Experimental Immunology and Virology

Russian Federation, 2 Lomonosovsky Ave, Bldg 1, Moscow, 119991

Ekaterina V. Freidlyn

National Medical Research Center for Children’s Health

Email: frdl-cito@mail.ru
ORCID iD: 0000-0002-5645-5181

Research Laboratory Assistant, Laboratory of Experimental Immunology and Virology

Russian Federation, 2/1, Lomonosovsky prospect., Moscow, 119296

Elena Kulebina

National Medical Research Center for Children’s Health

Email: Putintseva@mail.ru
ORCID iD: 0000-0001-9798-9617

Candidate of Medical Sciences, Acting Head of the Gastroenterology Department

Russian Federation, Ломоносовский пр-т 2 стр1

Elena L. Semikina

National Medical Research Center for Children’s Health;
I. Sechenov First Moscow State Medical University (Sechenov University)

Email: semikinaelena@yandex.ru
ORCID iD: 0000-0001-8923-4652
SPIN-code: 3647-4967

PhD, MD (Medicine), Chief Researcher, Head, Laboratory Department, National Medical Research Center of Children’s Health; Professor, Department of Pediatrics and Pediatric Rheumatology, Pediatric Faculty, I. Sechenov First Moscow State Medical University (Sechenov University)

Russian Federation, Moscow; Moscow

Alexander S. Potapov

National Medical Research Center for Children’s Health;
I. Sechenov First Moscow State Medical University (Sechenov University)

Email: potapov@nczd.ru
ORCID iD: 0000-0003-4905-2373

PhD, MD (Medicine), Professor, Chief Researcher, Professor, Department of Pediatrics and Pediatric Rheumatology

Russian Federation, 2 Lomonosovsky Ave, Bldg 1, Moscow, 119991; Moscow

Svetlana V. Petrichuk

National Medical Research Center for Children’s Health

Author for correspondence.
Email: cito@list.ru
ORCID iD: 0000-0003-0896-6996

PhD, MD (Biology), Professor,  Chief Scientist,  Laboratory of  Experimental Immunology and Virology

Russian Federation, 2/1, Lomonosovskiy Pr-t, Moscow, 119991

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Copyright (c) Kurbatova O.V., Movsisyan G.B., Radygina T.V., Fisenko A.P., Konyashin M.V., Zhuzhula A.A., Snovskaya M.A., Freidlyn E.V., Kulebina E., Semikina E.L., Potapov A.S., Petrichuk S.V.

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