CYTOKINE IMBALANCE AND COLLAGEN IV LEVEL IN CHRONIC HEPATITIS C PATIENTS WITH DIFFERENT ZINC CONTENTS

Derbak M. A., Sitkar A. D.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Introduction. Continuous replication of hepatitis C virus leads to a strong inflammatory response characterized by a large number of activated immune cells in the liver, as well as elevated levels of serum aminotransferases and pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). As a result, chronic damage to hepatocytes mediated by an ineffective immune response contributes to the development of liver fibrosis. In general, studies show that chronic zinc (Zn) deficiency occurs in chronic hepatitis C (CHC). As a result of HCV-mediated mitochondrial dysfunction, the presence of oxidative stress disrupts Zn homeostasis. With CHC, a decrease in the level of Zn can also be a consequence of liver fibrosis. The concentration of Zn in blood serum can also decrease due to the influence of pro-inflammatory cytokines, which have been proven to play an important role in the homeostasis of this trace element. Therefore, the question of the association of Zn content in blood serum with the severity of inflammation and liver fibrosis in patients with CHC remains open. The aim. To evaluate the levels of interleukins IL-1β, IL-4 and IL-6, TNF-α and collagen IV depending on the content of Zn in blood serum in patients with chronic hepatitis C. Materials and methods. 88 patients with a verified diagnosis of CHC were under observation, and the levels of Zn, interleukins IL-1β, IL-4, and IL-6, TNF-α, and collagen IV in blood serum were determined. Depending on the serum Zn level, all patients were divided into 2 groups: Group I – patients with a reduced level of Zn (n=42), Group II – patients with a normal level of Zn (n=46). Results. A higher frequency of moderate degree of inflammation (ALT above 5 norms) was observed in the group of patients with a reduced serum Zn level (23,8% vs. 6,5%, p=0,02). ALT activity was 1,8 times higher in the group of patients with a reduced level of Zn, compared to the group with a normal level of Zn (p=0,019), and the activity of AST is 1,6 times higher (p=0,024). It was found that in group I, the level of IL-1β was 1,5 times higher, and the level of IL-6 was 1,4 times higher (p<0,001), and the level of IL-4 was lower by 33,0%, compared to II group (p<0,001). It was shown that Zn was negatively correlated with the levels of IL-1β (ρ=–0,542, p<0,001), IL-6 (ρ=–0,556, p<0,001) and TNF-α (ρ=–0,476, p<0,001). On the contrary, there was a moderate positive correlation between Zn and IL-4 levels (ρ=0,485, p<0,001). It was also established that the level of collagen IV in the serum of patients of the I group was higher by 18,9% compared to the II group (p=0,036). A moderate negative correlation was found between serum Zn and collagen IV levels (ρ=–0,379, p<0,001). A higher frequency of higher degree of fibrosis (F3-F4) was observed in the group of patients with a reduced serum Zn level, compared to patients whose Zn level was within the normal range (52,5% vs. 32,6%). Conclusions. It was found that serum Zn level in patients with CHC is related to the activity of the inflammatory process and cytokine levels. A correlation between serum Zn and collagen IV levels and a higher frequency of a higher degree of fibrosis (F3-F4) in patients with a reduced serum Zn level compared to patients with a normal Zn level (52,5% vs. 32,6%) were shown. Therefore, Zn imbalance and its association with an active inflammatory process and the progression of liver fibrosis require further pathogenetic justifications.

chronic hepatitis C,zinc,inflammation,cytokines,fibrosis.

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«Bulletin of problems biology and medicine» Issue 4 (167), 2022 year, 131-137 pages, index UDK 616.36-002.2:577.118:612.017.1

10.29254/2077-4214-2022-4-167-131-137