CHANGES ANALYSIS OF THE HEPATOCYTE APOPTOSIS MARKERS LEVELS IN MALIGNANT OBSTRUCTIVE JAUNDICE COMPLICATED BY CHOLANGITIS

Abstract

The aim: To evaluate changes in the levels of hepatocyte apoptosis markers in malignant obstructive jaundice (MOJ) depending on the performance of preoperative biliary decompression (PBD) and the severity degree of primary ascending cholangitis (PAC). Materials and methods: 136 patients with MOJ complicated by cholangitis were included in the study: group A (n=84) – patients who underwent PBD; group B (n=52) – patients without PBD. The level of CASP3 and Bcl-2 (Human Bcl-2(B-cell Leukemia/Lymphoma 2) in blood serum and bile was assessed according to the principle of Sandwich-ELISA. Material collection for research was performed at the PBD stage and intraoperatively. Results: Comparative analysis of CASP3 levels in patients of the study groups revealed that the level of this indicator in the blood and bile of group A patients was statistically significantly higher compared to group B, p=0,004 and p<0,001, respectively. There was no statistically significant difference between the study groups in the intraoperative levels of blood serum Bcl-2 (p=0,786) and bile Bcl-2 (p=0,439). The presence of a correlation between apoptosis markers in group A patients with I and II degree of PAC at the time of PBD and the main surgical intervention was determined: blood serum CASP3 – r=0,733, p<0,001 and r=0,753, p<0,001; bile CASP3 – r=0,716, p<0,001 and r=0,792, p<0,001; blood serum Bcl-2 – r=0,609, p<0,001 and r=0,495, p=0,002; bile Bcl-2- r=0,744, p<0,001 and r=0,497, p=0,002, respectively. Binary logistic regression analysis showed that the development of grade I and II PAC did not relate with the levels of apoptosis markers (p>0.05). Linear regression analysis revealed a correlation between the levels of Bcl-2 in bile during PBD and intraoperatively in group A patients with moderate grade OJ (R2=0,547, p<0,001) and between the levels of CASP3 in blood serum (R2=0,614, p<0,001), CASP3 in bile (R2=0,603, p<0,001), Bcl-2 in blood serum (R2=0,484, p<0,001) and Bcl-2 in bile (R2=0,485, p<0,001) in PBD and intraoperatively in patients with severe grade OJ. A statistically significant difference in the levels of Bcl-2 in blood serum (p<0,001) and Bcl-2 in bile (p=0,016) was found when comparing apoptosis markers in patients with moderate grade OJ of the study groups. Binary logistic analysis showed that the performance of PBD had a significant (reducing) effect on CASP3 levels in blood serum and bile taken intraoperatively in study groups patients with moderate grade OJ (R2= 0,292, p<0,001; R2= 0,184, p<0,001). Conclusions: Prolonged OJ leads to the pathological apoptosis process. The performance of PBD statistically significantly reduces the level of CASP3 in blood serum and bile, which is confirmed by further determination intraoper¬atively in patients with OJ complicated by PAC, p<0,001. Staged surgical intervention with the performance of PBD according to clear indications is a necessary treatment strategy in patients with MOJ complicated by cholangitis.