53 -9 (83) 2025 - Abdulazizkhozhiev B.R., Aleynik V.A. - CHANGES IN DNA METHYLATION OF LEUCOCYTES AND STERILE INFLAMMATION OF THE BLOOD IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE AND CIRRHOSIS OF THE LIVER

CHANGES IN DNA METHYLATION OF LEUCOCYTES AND STERILE INFLAMMATION OF THE BLOOD IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE AND CIRRHOSIS OF THE LIVER

Abdulazizkhozhiev B.R. - Andijan State Medical Institute of Uzbekistan

Aleynik V.A. - Andijan branch of the Institute of Human Immunology and Genomics of the Academy of Sciences of the Republic of Uzbekistan

Zhuraeva M.A. - Andijan State Medical Institute of Uzbekistan

Babich S.M. - Andijan State Medical Institute of Uzbekistan

Resume

The work studied changes in DNA methylation of leukocytes and sterile inflammation of the blood in patients with non-alcoholic fatty liver disease and cirrhosis of the liver. It is concluded that the progression of non-alcoholic fatty liver disease (NAFLD) is accompanied by significant changes in the systemic cytokine profile: a significant increase in proinflammatory mediators (TNF-α, IL-1β, IL-1α, IL-33, HMGB1) and a significant decrease in the level of anti-inflammatory cytokine IL-10 are noted. These changes intensify as steatosis progresses to steatohepatitis and cirrhosis, confirming the leading role of chronic inflammation in the pathogenesis of the disease. Epigenetic disorders reflected by a decrease in DNMT1 activity and 5-mdC levels in leukocytes were detected already at the stage of steatohepatitis and become most pronounced in cirrhosis. These changes indicate the development of global DNA hypomethylation in immune cells, which can contribute to deregulation of the expression of genes involved in inflammation, immune response and fibrogenesis. DNA hypomethylation in leukocytes reflects not only local changes in the liver, but also systemic epigenetic rearrangement that contributes to the chronicity of inflammation and the formation of fibrosis. These markers can be considered as potential bioindicators of the disease stage, as well as targets for epigenetically targeted therapy. An increase in the level of HMGB1 and IL-33, as alarmins or DAMP molecules, enhances the inflammatory cascade and confirms the activation of cellular damage mechanisms and the innate immune response in severe forms of NAFLD. The level of uric acid consistently increases from steatosis to cirrhosis, indicating the involvement of metabolic disorders and oxidative stress in the pathogenesis of the disease. Taken together, the assessment of the cytokine profile, epigenetic markers (DNMT1, 5-mdC) and metabolic parameters (uric acid) is of diagnostic value for the early detection of progressive forms of NAFLD, risk assessment and personalization of therapeutic approaches.

Key words: non-alcoholic fatty liver disease, liver cirrhosis, interleukins, DNA methyltransferase 1, 5-methyl-2'-deoxycytidine, alarmins, epigenetic DNA methylatio

First page

325

Last page

331

For citation:Abdulazizkhozhiev B.R., Aleynik V.A., Zhuraeva M.A., Babich S.M. - CHANGES IN DNA METHYLATION OF LEUCOCYTES AND STERILE INFLAMMATION OF THE BLOOD IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE AND CIRRHOSIS OF THE LIVER//New Day in Medicine 9(83)2025 325-331 https://newdayworldmedicine.com/en/new_day_medicine/9-83-2025

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