Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis

Background. In recent years, as a result of the growing expansion of the pharmaceutical market, there has been a clear trend towards an increase in the incidence of chronic toxic drug-induced hepatitis of drug genesis (TDIH). The appearance of fibrosis is considered the most important histological c...

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Main Authors: V.I. Didenko, O.M. Tatarchuk, O.P. Petishko, I.S. Konenko, S.L. Melanich
Format: Article
Language:English
Published: Zaslavsky O.Yu. 2021-06-01
Series:Gastroenterologìa
Subjects:
Online Access:http://gastro.zaslavsky.com.ua/article/view/233629
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author V.I. Didenko
O.M. Tatarchuk
O.P. Petishko
I.S. Konenko
S.L. Melanich
author_facet V.I. Didenko
O.M. Tatarchuk
O.P. Petishko
I.S. Konenko
S.L. Melanich
author_sort V.I. Didenko
collection DOAJ
description Background. In recent years, as a result of the growing expansion of the pharmaceutical market, there has been a clear trend towards an increase in the incidence of chronic toxic drug-induced hepatitis of drug genesis (TDIH). The appearance of fibrosis is considered the most important histological change that determines the further course of the disease. Therefore, the search for non-invasive or minimally invasive markers for assessing fibrotic changes in the liver remains an urgent issue in clinical practice. The purpose was to determine the diagnostic value of immunological parameters for stratification of the severity of liver fibrosis in patients with TDIH. Materials and methods. The study included 41 patients with TDIH, who were divided into three groups: group I consisted of 12 people without liver fibrosis (F0), group II — 22 patients with moderate fibrosis (F1-F2), group III — 7 individuals with severe liver fibrosis (F3-F4). Shear wave elastography was performed using a Soneus P7 system (Ukraine-Switzerland). All patients underwent a biochemical blood test with the determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST). The subpopulation composition of lymphocytes, circulating immune complexes (CIC), the level of interleukins (IL-6, IL-10) and tumor necrosis factor α were assessed. Results. The progression of liver fibrosis is accompanied by an increase in cytolytic syndrome: patients with severe fibrosis have a 3.3-fold increase in the ALT (p < 0.05) compared to the controls and a 2.1-fold (p < 0.05) compared to that in patients with moderate fibrosis. The AST level is significantly higher — by 4.6 times (p = 0.023) in patients with severe fibrosis than in those with moderate fibrosis. With the progression of liver fibrosis, there is a significant decrease in cellular immunity, an increase in the level of CIC and pro-inflammatory cytokines with a simultaneous decrease in the content of anti-inflammatory cytokines, which is confirmed by correlations between the liver stiffness index according to shear wave elastography data and the level of T-helpers (r = –0.466; p = 0.03), IL-6 (r = 0.364; p = 0.01), IL-10 (r = –0.331; p = 0.039) and CIC (r = 0.381; p = 0.017). Conclusions. Markers of the diagnosis of severe liver fibrosis in patients with TDIH are indicators such as the ratio of IL-6/IL-10 higher than 0.83 (sensitivity 81.8 %, specificity 78.9 %), CIC level more than 4.3 optical density units (sensitivity 77.3 %, specificity 72.2 %), the ratio of T-helpers/T-suppressors is less than or equal to 1.6 (sensitivity 72.7 %, specificity 57.9 %).
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spelling doaj.art-5457ba312578488fb347364b100ebb092022-12-22T04:13:59ZengZaslavsky O.Yu.Gastroenterologìa2308-20972518-78802021-06-01552919710.22141/2308-2097.55.2.2021.233629271267Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitisV.I. Didenko0https://orcid.org/0000-0001-8953-396XO.M. Tatarchuk1https://orcid.org/0000-0002-0672-972XO.P. Petishko2https://orcid.org/0000-0002-4559-4055I.S. Konenko3https://orcid.org/0000-0002-7619-699XS.L. Melanich4https://orcid.org/0000-0003-3756-8882State Institution “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, UkraineState Institution “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, UkraineState Institution “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, UkraineState Institution “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, UkraineState Institution “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro, UkraineBackground. In recent years, as a result of the growing expansion of the pharmaceutical market, there has been a clear trend towards an increase in the incidence of chronic toxic drug-induced hepatitis of drug genesis (TDIH). The appearance of fibrosis is considered the most important histological change that determines the further course of the disease. Therefore, the search for non-invasive or minimally invasive markers for assessing fibrotic changes in the liver remains an urgent issue in clinical practice. The purpose was to determine the diagnostic value of immunological parameters for stratification of the severity of liver fibrosis in patients with TDIH. Materials and methods. The study included 41 patients with TDIH, who were divided into three groups: group I consisted of 12 people without liver fibrosis (F0), group II — 22 patients with moderate fibrosis (F1-F2), group III — 7 individuals with severe liver fibrosis (F3-F4). Shear wave elastography was performed using a Soneus P7 system (Ukraine-Switzerland). All patients underwent a biochemical blood test with the determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST). The subpopulation composition of lymphocytes, circulating immune complexes (CIC), the level of interleukins (IL-6, IL-10) and tumor necrosis factor α were assessed. Results. The progression of liver fibrosis is accompanied by an increase in cytolytic syndrome: patients with severe fibrosis have a 3.3-fold increase in the ALT (p < 0.05) compared to the controls and a 2.1-fold (p < 0.05) compared to that in patients with moderate fibrosis. The AST level is significantly higher — by 4.6 times (p = 0.023) in patients with severe fibrosis than in those with moderate fibrosis. With the progression of liver fibrosis, there is a significant decrease in cellular immunity, an increase in the level of CIC and pro-inflammatory cytokines with a simultaneous decrease in the content of anti-inflammatory cytokines, which is confirmed by correlations between the liver stiffness index according to shear wave elastography data and the level of T-helpers (r = –0.466; p = 0.03), IL-6 (r = 0.364; p = 0.01), IL-10 (r = –0.331; p = 0.039) and CIC (r = 0.381; p = 0.017). Conclusions. Markers of the diagnosis of severe liver fibrosis in patients with TDIH are indicators such as the ratio of IL-6/IL-10 higher than 0.83 (sensitivity 81.8 %, specificity 78.9 %), CIC level more than 4.3 optical density units (sensitivity 77.3 %, specificity 72.2 %), the ratio of T-helpers/T-suppressors is less than or equal to 1.6 (sensitivity 72.7 %, specificity 57.9 %).http://gastro.zaslavsky.com.ua/article/view/233629chronic toxic drug-induced hepatitis, liver fibrosis, diagnostic markers
spellingShingle V.I. Didenko
O.M. Tatarchuk
O.P. Petishko
I.S. Konenko
S.L. Melanich
Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis
Gastroenterologìa
chronic toxic drug-induced hepatitis, liver fibrosis, diagnostic markers
title Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis
title_full Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis
title_fullStr Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis
title_full_unstemmed Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis
title_short Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis
title_sort markers of progression of liver fibrotic changes in patients with chronic toxic drug induced hepatitis
topic chronic toxic drug-induced hepatitis, liver fibrosis, diagnostic markers
url http://gastro.zaslavsky.com.ua/article/view/233629
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AT oppetishko markersofprogressionofliverfibroticchangesinpatientswithchronictoxicdruginducedhepatitis
AT iskonenko markersofprogressionofliverfibroticchangesinpatientswithchronictoxicdruginducedhepatitis
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