CORRELATION OF APOPTOSIS MARKERS LEVELS WITH THE DEVELOPMENT OF HEPATIC FAILURE IN MALIGNANT OBSTRUCTIVE JAUNDICE

Authors

  • O. DRONOV Bogomolets National Medical University, First Department of General Surgery, Kyiv, Ukraine
  • I. KOVALSKA Bogomolets National Medical University, First Department of General Surgery, Kyiv, Ukraine
  • L. ROSHCHYNA Bogomolets National Medical University, First Department of General Surgery, Kyiv, Ukraine
  • L. LEVCHENKO Bogomolets National Medical University, First Department of General Surgery, Kyiv, Ukraine
  • D. VLASENKO Bogomolets National Medical University, First Department of General Surgery, Kyiv, Ukraine

DOI:

https://doi.org/10.15407/exp-oncology.2025.01.068

Keywords:

apoptosis, jaundice, biliary decompression, hepatic failure

Abstract

Obstructive jaundice (OJ) is a common diagnosis in everyday clinical practice, which requires a thorough understanding of pathophysiological changes occurring in the liver to plan ongoing treatment and predict its effectiveness in the postoperative period. The study aimed to determine the dynamics of changes in the levels of apoptosis markers (caspase-3 and BCL-2) at the time of preoperative biliary decompression (PBD) and major surgery depending on the severity of the hepatic failure (HF) and to evaluate their correlation with the severity grade of HF in patients with malignant obstructive jaundice (MOJ). Materials and Methods. The study included 104 patients with MOJ who underwent PBD. All patients were diagnosed with HF of moderate severity (n = 65) or severe HF (n = 39). During PBD and main surgical intervention, the levels of caspase-3 and BCL-2 were determined in blood serum and bile by the Sandwich-ELISA method. Results. The values of apoptosis markers in patients with moderate and severe HF were significantly different at the time of PBD and major surgery (p < 0.001). PBD significantly reduced the levels of caspase-3 and increased the levels of BCL-2 in sera of patients with MOJ and HF, which was confirmed by further intraoperative values of the indicators, p < 0.001. Imbalance of serum caspase-3 (R2 Nagelkerke = 0.553, p = 0.013) and BCL-2 (R2 Nagelkerke = 0.327, p = 0.003) levels was associated with severe HF. Conclusions. The indicators of apoptosis after PBD can serve as additional markers of the effectiveness of a patient’s treatment in the preoperative period and can be included in the diagnostic and therapeutic algorithm for patients with MOJ.

References

Liu JJ, Sun YM, Xu Y, et al. Pathophysiological consequences and treatment strategy of obstructive jaundice. World J Gastrointest Surg. 2023;15(7):1262. https://doi.org/10.4240/wjgs.v15.i7.1262

Soares PFDC, Gestic MA, Utrini MP, et al. Epidemiological profile, referral routes and diagnostic accuracy of cases of acute cholangitis among individuals with obstructive jaundice admitted to a tertiary-level university hospital: a cross-sectional study. Sao Paulo Med. J. 2019;137:491-497. https://doi.org/10.1590/1516-3180.2019.0109170919

Kurniawan J, Hasan I, Gani RA. Mortality-related factors in patients with malignant obstructive jaundice. Acta Med Indones. 2016;48:282-288. PMID: 28143989

Hong, JY, Sato EF, Hiramoto K, et al. Mechanism of liver injury during obstructive jaundice: role of nitric oxide, splenic cytokines, and intestinal flora. J Clin Biochem Nutr. 2007;40(3):184-193. https://doi.org/10.3164/jcbn.40.184

Donald W, Nicholson DW, Thornberry NA. Killer protease. Trends Biochem Sci. 1998;22(8):299-306. https://doi. org/:10.1083/jcb.140.6.1485

Xu F, Dai CL, Peng SL, et al. Preconditioning with glutamine protects against ischemia/reperfusion-induced hepatic injury in rats with obstructive jaundice. Pharmacology. 2014;93(3-4):155-165. https://doi.org/:10. 1159/000360181

Zhou M, Zhang Q, ZhaoJ, et al. Phosphorylation of Bcl-2 plays an important role in glycochenodeoxycholate-induced survival and chemoresistance in HCC. Oncol Rep. 2017;38(3):1742-1750. https://doi.org/:10.3892/or.2017.5830

Drichits ОА, Kiziukevich LS, Kapytski AV, et al. Experimental subhepatic obstructive jaundice and BCL-2 gene expression. Biol Markers Fundam Clin Med. 2019;3(2):4-5. https://doi.org/:10.29256/v.03.02.2019.escbm01

Dronov OI, Kovalska IO, Kozachuk YS, et al. Сhanges analysis of the hepatocyte apoptosis markers levels in ma- lignant obstructive jaundice complicated by cholangitis. Wiad Lek. 2023;76(3):560-567. https://doi.org/:10.36740/ WLek202303115

National Cancer Institute Available from: https://unci.org.ua/standarty-diagnostyky-ta-likuvannya/

National Comprehensive Cancer Network (NCCN Guidelines) Available from: https://www.nccn.org/guidelines/ category_1

Donelli MG, Zucchetti M, Munzone E, et al. Pharmacokinetics of anticancer agents in patients with impaired liver function. Eur J Cancer. 1998;34:33-46. https://doi.org/10.1016/s0959-8049(97)00340-7

Tchambaz L, Schlatter C, Jakob M, et al. Dose adaptation of antineoplastic drugs in patients with liver disease. Drug Safety. 2006;29(6):509-522. https://doi.org/10.2165/00002018-200629060-00004

Xing TJ. Clinical classification of liver failure: consensus, contradictions and new recommendations. J Clin Gastro- enterol Hepatol. 2017;1(2). https://doi.org/10.21767/2575-7733.1000016

Tokyo Guidelines recommendation, 2018. Available from: http://onlinelibrary.wiley.com/doi/10.1002/jhbp.512/full

Shen Z, Zhang J, Zhao S, et al. Preoperative biliary drainage of severely obstructive jaundiced patients decreases overall postoperative complications after pancreaticoduodenectomy: a retrospective and propensity score-matched analysis. Pancreatology. 2020;20(3):529-536. https://doi.org/10.1016/j.pan.2020.02.002

Shojaie L, Iorga A, Dara L. Cell death in liver diseases: a review. Int J Mol Sci. 2020;21(24):9682. https://doi. org/10.3390/ijms21249682

Guicciardi ME, Gores GJ. Apoptosis: a mechanism of acute and chronic liver injury. Gut. 2020;54(7):1024-1033. https://doi.org/10.1136/gut.2004.053850

Sodeman T, Bronk SF, Roberts PJ, et al. Bile salts mediate hepatocyte apoptosis by increasing cell surface trafficking of Fas. Am J Physiol Gastrointest Liver Physiol. 2000;278:G992-G999. https://doi.org/10.1152/ajpgi.2000.278.6.G992

Wang K. Molecular mechanisms of hepatic apoptosis. Cell Death Dis. 2014;5(1):e996-e996. https://doi.org/10.1038/ cddis.2013.499

Elsaied N, Samy A, Mosbah E, et al. Induction of surgical obstructive cholestasis in rats: morphological, bio- chemical and immunohistochemical changes. Mansoura Vet Med J. 2020;21(3):107-115. https://doi.org/:10.21608/ mvmj.2020.21.318

Zhang Y, Liu C, Barbier O, et al. Bcl2 is a critical regulator of bile acid homeostasis by dictating Shp and lncRNA H19 function. Sci Rep. 2016;3(6):20559. https://doi.org/:10.1038/srep20559

Nzeako UC, Guicciardi ME, Yoon JH, et al. COX‐2 inhibits Fas‐mediated apoptosis in cholangiocarcinoma cells.

Hepatology. 2002;35(3):552-559. https://doi.org/:10.1053/jhep.2002.31774

Mancini M, Nicholson DW, Roy S, et al. The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling. J Cell Biol. 1998;140(6):1485-1495. https://doi.org/:10.1083/jcb.140.6.1485

Persad R, Liu C, Wu TT, et al. Overexpression of caspase-3 in hepatocellular carcinomas. Mod Pathol. 2004;17(7):861- 867. https://doi.org/:10.1038/modpathol.3800146

Downloads

Published

11.07.2025

How to Cite

DRONOV, O., KOVALSKA, I., ROSHCHYNA, L., LEVCHENKO, L., & VLASENKO, D. (2025). CORRELATION OF APOPTOSIS MARKERS LEVELS WITH THE DEVELOPMENT OF HEPATIC FAILURE IN MALIGNANT OBSTRUCTIVE JAUNDICE. Experimental Oncology, 47(1), 68–75. https://doi.org/10.15407/exp-oncology.2025.01.068

Issue

Section

Original contributions