Biochemical and molecular-genetic indicators of inflammation and apoptosis in liver cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis

Aim. A comparative analysis of the complex of clinical and laboratory indicators (including the content of cytokines in blood plasma and the level of expression of TNF and IL6 genes in peripheral leukocytes, as well as the level of biochemical and molecular-genetic indicators of apoptosis, such as t...

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Main Authors: I V Kurbatova, L V Topchieva, O P Dudanova, A A Shipovskaya
Format: Article
Language:Russian
Published: "Consilium Medicum" Publishing house 2019-04-01
Series:Терапевтический архив
Subjects:
Online Access:https://ter-arkhiv.ru/0040-3660/article/viewFile/33565/pdf
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author I V Kurbatova
L V Topchieva
O P Dudanova
A A Shipovskaya
author_facet I V Kurbatova
L V Topchieva
O P Dudanova
A A Shipovskaya
author_sort I V Kurbatova
collection DOAJ
description Aim. A comparative analysis of the complex of clinical and laboratory indicators (including the content of cytokines in blood plasma and the level of expression of TNF and IL6 genes in peripheral leukocytes, as well as the level of biochemical and molecular-genetic indicators of apoptosis, such as the content of tissue polypeptide-specific antigen (TPS) in the blood, the activity of caspases 3, 8 and 9 and the expression level of the encoding genes in peripheral blood leukocytes) in patients with non-alcoholic fatty liver disease (NAFLD) with non-alcoholic steatohepatitis (NASH) of different activity, liver cirrhosis (LC) classes A and B and in the donors of control group. Materials and methods. 158 patients with NAFLD were examined: 116 patients with NASH diagnosed for the first time (NASH of weak, moderate and high activity) and 42 patients with the NAFLD at the stage of liver cirrhosis diagnosed for the first time (classes A and B according to the Child-Pugh classification). The control group consisted of 54 healthy donors. The clinical blood biochemistry, cytokine profile, tissue polypeptide-specific antigen content, the level of the TNF, IL6 gene and caspase gene transcription as well as caspase activity in peripheral blood leukocytes (PBL) were evaluated. Results and discussion. In the progression of NASH to LC, together with changes in general clinical parameters, the cytokine profile are changed due to an increase in the level of IL-6 and IL-1β; in peripheral leukocytes, the activity of caspase 9 increases and the activity of caspase 8 decreases compared to NASH, and the level of the TNF gene expression decreases as compared to NASH of high activity. These parameters can be considered as promising minimally invasive markers of progression of NAFLD to LC. Conclusion. In nonalcoholic cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis changes in clinical parameters (indicating the development of hepatocellular deficiency, violation of protein and lipid metabolism, progressive inflammation) are accompanied by specific changes in levels of biochemical and molecular-genetic indicators of apoptosis and inflammation. With the progression of NASH to LC, the cytokine profile changes due to an increase in the level of proinflammatory cytokines, the apoptosis processes triggered by the internal pathway increase and the activity of apoptosis activated via the external pathway decreases in PBL
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spelling doaj.art-63c09ea3fc934c2f8a3f0307d7a9f0642022-12-21T20:34:26Zrus"Consilium Medicum" Publishing houseТерапевтический архив0040-36602309-53422019-04-01914212710.26442/00403660.2019.04.00005730295Biochemical and molecular-genetic indicators of inflammation and apoptosis in liver cirrhosis as an outcome of the progression of non-alcoholic steatohepatitisI V Kurbatova0L V Topchieva1O P Dudanova2A A Shipovskaya3Institute of Biology of the Karelian Research Centre of the Russian Academy of Sciences (IB KarRC RAS), Laboratory for GeneticsInstitute of Biology of the Karelian Research Centre of the Russian Academy of Sciences (IB KarRC RAS), Laboratory for GeneticsPetrozavodsk State University, Institute of Medicine, Department of Propaedeutics of Internal Diseases and HygienePetrozavodsk State University, Institute of Medicine, Department of Propaedeutics of Internal Diseases and HygieneAim. A comparative analysis of the complex of clinical and laboratory indicators (including the content of cytokines in blood plasma and the level of expression of TNF and IL6 genes in peripheral leukocytes, as well as the level of biochemical and molecular-genetic indicators of apoptosis, such as the content of tissue polypeptide-specific antigen (TPS) in the blood, the activity of caspases 3, 8 and 9 and the expression level of the encoding genes in peripheral blood leukocytes) in patients with non-alcoholic fatty liver disease (NAFLD) with non-alcoholic steatohepatitis (NASH) of different activity, liver cirrhosis (LC) classes A and B and in the donors of control group. Materials and methods. 158 patients with NAFLD were examined: 116 patients with NASH diagnosed for the first time (NASH of weak, moderate and high activity) and 42 patients with the NAFLD at the stage of liver cirrhosis diagnosed for the first time (classes A and B according to the Child-Pugh classification). The control group consisted of 54 healthy donors. The clinical blood biochemistry, cytokine profile, tissue polypeptide-specific antigen content, the level of the TNF, IL6 gene and caspase gene transcription as well as caspase activity in peripheral blood leukocytes (PBL) were evaluated. Results and discussion. In the progression of NASH to LC, together with changes in general clinical parameters, the cytokine profile are changed due to an increase in the level of IL-6 and IL-1β; in peripheral leukocytes, the activity of caspase 9 increases and the activity of caspase 8 decreases compared to NASH, and the level of the TNF gene expression decreases as compared to NASH of high activity. These parameters can be considered as promising minimally invasive markers of progression of NAFLD to LC. Conclusion. In nonalcoholic cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis changes in clinical parameters (indicating the development of hepatocellular deficiency, violation of protein and lipid metabolism, progressive inflammation) are accompanied by specific changes in levels of biochemical and molecular-genetic indicators of apoptosis and inflammation. With the progression of NASH to LC, the cytokine profile changes due to an increase in the level of proinflammatory cytokines, the apoptosis processes triggered by the internal pathway increase and the activity of apoptosis activated via the external pathway decreases in PBLhttps://ter-arkhiv.ru/0040-3660/article/viewFile/33565/pdfnon-alcoholic fatty liver disease (nafld)liver cirrhosisinflammationcytokinesapoptosis
spellingShingle I V Kurbatova
L V Topchieva
O P Dudanova
A A Shipovskaya
Biochemical and molecular-genetic indicators of inflammation and apoptosis in liver cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis
Терапевтический архив
non-alcoholic fatty liver disease (nafld)
liver cirrhosis
inflammation
cytokines
apoptosis
title Biochemical and molecular-genetic indicators of inflammation and apoptosis in liver cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis
title_full Biochemical and molecular-genetic indicators of inflammation and apoptosis in liver cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis
title_fullStr Biochemical and molecular-genetic indicators of inflammation and apoptosis in liver cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis
title_full_unstemmed Biochemical and molecular-genetic indicators of inflammation and apoptosis in liver cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis
title_short Biochemical and molecular-genetic indicators of inflammation and apoptosis in liver cirrhosis as an outcome of the progression of non-alcoholic steatohepatitis
title_sort biochemical and molecular genetic indicators of inflammation and apoptosis in liver cirrhosis as an outcome of the progression of non alcoholic steatohepatitis
topic non-alcoholic fatty liver disease (nafld)
liver cirrhosis
inflammation
cytokines
apoptosis
url https://ter-arkhiv.ru/0040-3660/article/viewFile/33565/pdf
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