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EFFECT OF ALPHA-1-DEFENSIN ON THE LEVEL OF ENDOTOXINEMIA IN LIVER CIRRHOSIS

Keywords: liver cirrhosis, endotoxinemia, lipopolysaccharide, alpha-1-defensin, nonspecific resistance factors

Abstract

Background. Endotoxinemia is an important link in the pathogenesis of liver cirrhosis and its complications. At the same time, the impaired production of nonspecific humoral defense factors of the immunity system can also lead to the
development of endotoxinemia. Objective. To evaluate the influence of alpha-1-defensin, as a nonspecific humoral defense factor of the body, on the development of endotoxinemia. Material and methods. The study was conducted in accordance with the parallel-group controlled study protocol (with a control group receiving standard care of an underlying disorder) in the departments of Gastroenterology and Anesthesiology and Resuscitation of Vitebsk regional clinical specialized center. The study included 34 patients with alcohol-related liver cirrhosis. The experimental group included 23 practically healthy people. Lipopolysaccharide and alpha-1-defensin levels were determined by ELISA method using Human LPS ELISA Kit, Human DEFA1 ELISA Kit, respectively. Results. The study found that the serum LPS level in patients with cirrhosis was higher (91.4; 67.95 - 99.97 pg/mL) than that in the experimental group (64.0; 49.88 - 71.51 pg/mL, Z=3.99, p=0.00003). The serum DEFA1 level in patients with cirrhosis was also higher (370.46; 260.96 - 408.83 pg/mL) than that in the experimental group (181.5; 130.38 - 276.6 pg/mL, Z=2.4, p=0.014). There was a strong inverse correlation between serum LPS and DEFA1 levels in patients with cirrhosis (r=-0.79, p<0.05). Conclusion. The patients with liver cirrhosis had a statistically significant increase in serum levels of lipopolysaccharide and alpha-1-defensin, there being a strong inverse correlation of the studied parameters. Moreover, an increase in the level of LPS in the blood serum alongside with relatively lower levels of DEFA1 is observed in a number of patients with
liver cirrhosis, that is confirmed by a strong inverse correlation of the studied parameters. Such changes indicate that the decrease in the activity of nonspecific humoral defense factors of the body leads to the accumulation of bacterial
endotoxins in blood serum, which further contributes to the development of complications of liver cirrhosis.

References

Seo YS, Shah VH. The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension. Clin Mol Hepatol. 2012;18(4):337-346. https://doi.org/10.3350/cmh.2012.18.4.337.

Artis D. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol. 2008;8(6):411-420. https://doi.org/10.1038/nri2316.

Bull-Otterson L, Feng W, Kirpich I, Wang Y, Qin X, Liu Y, Gobejishvili L, Joshi-Barve S, Ayvaz T, Petrosino J, Kong M, Barker D, McClain C, Barve S. Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment. PLoS One. 2013;8(1):e53028. https://doi.org/10.1371/journal.pone.0053028.

Bajaj JS, Heuman DM, Hylemon PB, Sanyal AJ, White MB, Monteith P, Noble NA, Unser AB, Daita K, Fisher AR, Sikaroodi M, Gillevet PM. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol. 2014;60(5):940-947. https://doi.org/10.1016/j.jhep.2013.12.019.

Chen Y, Yang F, Lu H, Wang B, Chen Y, Lei D, Wang Y, Zhu B, Li L. Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology. 2011;54(2):562-572. https://doi.org/10.1002/hep.24423.

Mutlu EA, Gillevet PM, Rangwala H, Sikaroodi M, Naqvi A, Engen PA, Kwasny M, Lau CK, Keshavarzian A. Colonic microbiome is altered in alcoholism. Am J Physiol Gastrointest Liver Physiol. 2012;302(9):G966-G978. https://doi.org/10.1152/ajpgi.00380.2011.

Liu Q, Duan ZP, Ha DK, Bengmark S, Kurtovic J, Riordan SM. Synbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis. Hepatology. 2004;39(5):1441-9. https://doi.org/10.1002/hep.20194.

Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L, Guo J, Le Chatelier E, Yao J, Wu L, Zhou J, Ni S, Liu L, Pons N, Batto JM, Kennedy SP, Leonard P, Yuan C, Ding W, Chen Y, Hu X, Zheng B, Qian G, Xu W, Ehrlich SD, Zheng S, Li L. Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014;513(7516):59-64. https://doi.org/10.1038/nature13568.

Pryshchepenka VA, Yupatau GI, Svirko DA, Shuverova KV, Denisenko NV. Osobennosti mikroorganizmov tolstogo kishechnika u pacientov s cirrozom pecheni. In: Asirjan EG, Adaskevich VP, Alekseenko YV, Bekish VJa, Bolshakov LV, Vyhristenko LR, Glushanko VS, Kadushko RV, Karpuk IJu, Kiseleva NI, Kozlovskij VI, Kulik SP, Kuncevich ZS, Novikova VI, Petuhov VI, Podpalov VP, Semenov VM, Tihonova LV, Hishova OM, editors. Dostizhenija fundamentalnoj, klinicheskoj mediciny i farmacii. Materialy 78 nauchnoj sessii VGMU; 2023 Jan. 25-26; Vitebsk [Internet]. Vitebsk: VGMU; 2023. edn: NOCHJB. Available from: https://elib.vsmu.by/handle/123/25100 (Russian).

Wilde B, Katsounas A. Immune Dysfunction and Albumin-Related Immunity in Liver Cirrhosis. Mediators Inflamm. 2019;2019:7537649. https://doi.org/10.1155/2019/7537649.

An L, Wirth U, Koch D, Schirren M, Drefs M, Koliogiannis D, Nieß H, Andrassy J, Guba M, Bazhin AV, Werner J, Kühn F. The Role of Gut-Derived Lipopolysaccharides and the Intestinal Barrier in Fatty Liver Diseases. J Gastrointest Surg. 2022;26(3):671-683. https://doi.org/10.1007/s11605-021-05188-7.

Sipeki N, Antal-Szalmas P, Lakatos PL, Papp M. Immune dysfunction in cirrhosis. World J Gastroenterol. 2014;20(10):2564-2577. https://doi.org/10.3748/wjg.v20.i10.2564.

Ehmann D, Wendler J, Koeninger L, Larsen IS, Klag T, Berger J, Marette A, Schaller M, Stange EF, Malek NP, Jensen BAH, Wehkamp J. Paneth cell α-defensins HD-5 and HD-6 display differential degradation into active antimicrobial fragments. Proc Natl Acad Sci U S A. 2019;116(9):3746-3751. https://doi.org/10.1073/pnas.1817376116.

Ibusuki R, Uto H, Oda K, Ohshige A, Tabu K, Mawatari S, Kumagai K, Kanmura S, Tamai T, Moriuchi A, Tsubouchi H, Ido A. Human neutrophil peptide-1 promotes alcohol-induced hepatic fibrosis and hepatocyte apoptosis. PLoS One. 2017;12(4):e0174913. https://doi.org/10.1371/journal.pone.0174913.

Aceti A, Mangoni ML, Pasquazzi C, Fiocco D, Marangi M, Miele R, Zechini B, Borro M, Versace I, Simmaco M. Alpha-defensin increase in peripheral blood mononuclear cells from patients with hepatitis C virus chronic infection. J Viral Hepat. 2006;13(12):821-827. https://doi.org/10.1111/j.1365-2893.2006.00762.x.

Pryschepenko VA, Yupatov GI, Okulich VK. Study of Interleukin-13 and Alpha-1-defensin levels in patients with chronic diffuse liver diseases. Immunopathology, allergology, infectology. 2018;4:87-95. https://doi.org/10.14427/jipai.2018.4.87. https://www.elibrary.ru/evsjhs. (Russian).

Pryshchepenka V, Yupatau H, Akulich V, Generalau I, Ypatava Z. Features of the level of human beta-1-defensin in patients with alcohol-related liver diseases. In: 28th United European Gastroenterology Week Virtual; 2020 Okt. 11-13; Vienna, Austria. Vienna; 2020. p. 585. (United European Gastroenterology Journal; vol. 8, suppl. 8). https://doi.org/10.1177%2F205064062000800801.

Published
2025-12-17
How to Cite
1.
Pryshchepenka VA, Yupatau G. EFFECT OF ALPHA-1-DEFENSIN ON THE LEVEL OF ENDOTOXINEMIA IN LIVER CIRRHOSIS. journalHandG [Internet]. 2025Dec.17 [cited 2025Dec.19];9(2):108-12. Available from: http://www.journal-grsmu.by/index.php/journalHandG/article/view/376
Section
Оригинальные исследования