恶性胆道梗阻介入术后胆道感染患者TLR2 mRNA、HDC和CD64表达特征及预测价值

Expression characteristics and predictive value of TLR2 mRNA, HDC, and CD64 for biliary infection after interventional therapy for malignant biliary obstruction

摘要:

背景与目的 胆道感染是恶性胆道梗阻介入治疗后的常见并发症之一，但目前缺乏有效的早期预测指标。本研究探讨Toll样受体2（TLR2）mRNA、组氨酸脱羧酶（HDC）及中性粒细胞CD64在恶性胆道梗阻患者数字减影血管造影（DSA）引导胆道支架联合放射性粒子链植入术后胆道感染的表达变化及其预测价值。方法 回顾性纳入2021年1月—2024年2月河北省邢台市人民医院285例接受DSA引导胆道支架联合放射性粒子链植入术的恶性胆道梗阻患者，根据术后是否发生胆道感染分为感染组（46例）和未感染组（239例）。比较两组基线资料及术前、术后1 d炎症指标［C-反应蛋白（CRP）、降钙素原（PCT）、白细胞］及TLR2 mRNA、HDC、CD64水平。采用Pearson相关分析，评价其与CRP的相关性，采用多因素Logistic回归分析影响因素，并通过受试者工作特征曲线（ROC）评估其预测价值。另纳入2024年3月—2024年10月50例患者进行前瞻性验证。结果 感染组糖尿病、胆结石及高位梗阻比例高于未感染组（均P<0.05）。术后1 d感染组CRP、TLR2 mRNA、HDC及CD64水平均高于未感染组（均P<0.05）。TLR2 mRNA、HDC及CD64与CRP水平均呈正相关（r=0.729、0.682、0.755，均P<0.05），并与感染严重程度呈正相关。多因素Logistic回归分析显示，校正糖尿病、胆结石及梗阻类型后，TLR2 mRNA、HDC及CD64仍为术后胆道感染的独立相关因素（均P<0.05）。ROC分析显示三者联合预测术后胆道感染的曲线下面积为0.923，敏感度为89.13%，特异度为84.10%，优于单项指标。前瞻性验证结果显示预测模型与实际结果一致性良好（κ=0.864）。结论 恶性胆道梗阻患者DSA引导胆道支架联合放射性粒子链植入术后TLR2 mRNA、HDC及CD64水平升高与胆道感染发生相关，三者联合检测具有较高的早期预测价值，可为术后胆道感染的早期识别提供参考。

Abstract:

Background and Aims Biliary tract infection is a common complication after interventional treatment for malignant biliary obstruction (MBO), yet reliable early predictive markers are lacking. This study aimed to investigate the expression of Toll-like receptor 2 (TLR2) mRNA, histidine decarboxylase (HDC), and neutrophil CD64 and evaluate their predictive value for postoperative biliary infection after DSA-guided biliary stent combined with radioactive seed chain implantation.Methods A retrospective cohort of 285 patients with MBO who underwent DSA-guided biliary stent combined with radioactive seed chain implantation between January 2021 and February 2024 was analyzed. Patients were divided into an infection group (n=46) and a non-infection group (n=239) according to the occurrence of postoperative biliary infection. Baseline characteristics, inflammatory markers (CRP, PCT, and white blood cells), and the expression levels of TLR2 mRNA, HDC, and CD64 before surgery and on postoperative day 1 were compared. Pearson correlation analysis was performed to evaluate correlations with CRP levels. Multivariate logistic regression was used to identify independent factors associated with postoperative infection. Receiver operating characteristic (ROC) curves were used to assess predictive performance. An additional prospective cohort of 50 patients (March-October 2024) was used for validation.Results The proportions of diabetes, gallstones, and high-level obstruction were significantly higher in the infection group (all P<0.05). On postoperative day 1, levels of CRP, TLR2 mRNA, HDC, and CD64 were significantly higher in the infection group than in the non-infection group (all P<0.05). TLR2 mRNA, HDC, and CD64 levels were positively correlated with CRP (r=0.729, 0.682, and 0.755, respectively; all P<0.05) and infection severity. After adjusting for diabetes, gallstones, and obstruction level, TLR2 mRNA, HDC, and CD64 remained independent factors associated with postoperative biliary infection (all P<0.05). ROC analysis showed that the combined detection of TLR2 mRNA, HDC, and CD64 achieved an AUC of 0.923, with a sensitivity of 89.13% and specificity of 84.10%. Prospective validation demonstrated good agreement between predicted and actual outcomes (κ=0.864).Conclusion Elevated levels of TLR2 mRNA, HDC, and CD64 are associated with postoperative biliary infection in patients with malignant biliary obstruction. Combined detection of these biomarkers may serve as a promising strategy for early prediction of postoperative biliary infection.