血细胞计数相关标志物对慢加急性乙型肝炎肝衰竭患者28天预后的诊断价值

doi:10.6040/j.issn.1671-7554.0.2024.1354

摘要/Abstract

摘要： 目的探讨血细胞计数相关标志物对慢加急性乙型肝炎肝衰竭(acute-on-chronic hepatitis B liver failure, ACHBLF)患者28天预后的诊断价值。方法回顾性纳入2010年1月至2024年7月在山东大学齐鲁医院肝病科住院的ACHBLF患者,单因素和多因素Logistic回归分析筛选患者28 d预后的风险因素,机器学习XGBoost算法评估风险因素效应值,受试者工作特征(receiver operator characteristic, ROC)曲线评估标志物对ACHBLF患者预后判断的准确度,校准曲线评估标志物的校准度,Kaplan-Meier生存曲线评估患者28 d预后。结果共纳入ACHBLF患者261例,其中99例(37.93%)在28 d内死亡。与生存组相比,死亡组血细胞计数相关标志物(中性粒细胞+单核细胞)/淋巴细胞比值［(neutrophil + monocyte)to lymphocyte ratio, NmLR］、全身炎症反应指数(systemic inflammatory response index, SIRI)和中性粒细胞/血小板比值(neutrophil-to-platelet ratio, NPR)显著升高。单因素Logistic回归分析显示年龄、白蛋白、血钠离子、嗜酸性粒细胞比率、嗜酸性粒细胞计数、凝血酶原活动度(prothrombin activity, PTA)、国际标准化比值(international normalized ratio, INR)、总胆红素(total bilirubin, TBIL)、终末期肝病模型(model for end-stage liver disease, MELD)评分、NmLR、SIRI及NPR为ACHBLF患者28 d生存结局的影响因素。多因素Logistic回归分析显示,SIRI(OR=1.15,95%CI:1.03~1.29,P=0.011)和MELD评分(OR=1.23,95%CI:1.14~1.31,P<0.001)是患者28 d预后的独立风险因素,机器学习XGBoost算法提示MELD评分和SIRI的SHAP值分别为0.839和0.278。SIRI诊断ACHBLF患者28 d不良预后的ROC曲线下面积(area under the curve, AUC)为0.693(95%CI:0.628~0.758),特异度为0.469,敏感度为0.828,联合MELD评分的AUC为0.807(95%CI:0.753~0.861),特异度为0.772,灵敏度为0.727,表现出良好的校准度。Kaplan-Meier分析显示,SIRI联合MELD评分模型>1.9的患者生存时间显著低于≤1.9的患者(P=0.012)。在符合中国标准的ACHBLF患者中,SIRI联合MELD评分诊断ACHBLF患者28 d不良预后的AUC为0.749(95%CI:0.677~0.820),特异度为0.677,灵敏度为0.733,同样表现出良好的诊断效能。结论 SIRI联合MELD评分可用于评估慢加急性乙型肝炎肝衰竭患者的28 d预后。

关键词: 慢加急性乙型肝炎肝衰竭, 全身炎症反应指数, 预后, 风险因素, 血细胞计数相关标志物

Abstract: Objective To investigate the diagnostic value of blood cell count-related biomarkers in predicting 28-day morality in patients with acute-on-chronic hepatitis B liver failure(ACHBLF). Methods A total of 261 patients with ACHBLF were retrospectively included from January 2010 to July 2024. Univariate and multivariate Logistic regression analyses were performed to identify the risk factors, which were further evaluated by machine learning using XGBoost algorithm. The receiver operating characteristic(ROC)curve was analyzed to evaluate the prognostic accuracy and the calibration curve was used to evaluate the calibration. Furthermore, Kaplan-Meier survival analysis was performed to evaluate the performance of the model in diagnosing the 28-day mortality. Results There were 99(37.93%)patients who died within 28 days. Univariate Logistic regression analysis identified age, albumin, serum sodium, eosinophil ratio, eosinophil count, prothrombin activity(PTA), international normalized ratio(INR), total bilirubin(TBIL), model for end-stage liver disease(MELD)score,(neutrophil+monocyte)/lymphocyte ratio(NmLR), systemic inflammatory response index(SIRI), and neutrophil/platelet ratio(NPR)as risk factors. Multivariate Logistic regression analysis showed that SIRI(OR=1.15,95%CI:1.03-1.29,P=0.011)and MELD score(OR=1.23,95%CI:1.14-1.31,P<0.001)were independent risk factors for 28-day mortality. XGBoost algorithm showed that the SHAP values of SIRI and MELD score were 0.278 and 0.839, respectively. The area under the ROC curve(AUC)of SIRI was 0.693(95%CI: 0.628-0.758)with a specificity of 0.469 and a sensitivity of 0.828. In addition, the combination of SIRI and MELD score showed an AUC of 0.807(95%CI: 0.753-0.861)with a specificity of 0.722 and a sensitivity of 0.727. The calibration curve showed that the predicted probability was consistent with the actual probability. Kaplan-Meier analysis showed that patients with a combined diagnostic score above the cut-off value of 1.9 had a worse survival than those with a combined diagnostic score below 1.9(P=0.012). In ACHBLF patients diagnosed by Chinese criteria, the combination of SIRI and MELD score showed an AUC of 0.749(95%CI: 0.677-0.820)with a specificity of 0.677 and a sensitivity of 0.733, validating the performance of the combined model in predicting 28-day prognosis. Conclusion SIRI combined with MELD score has good diagnostic value for predicting 28-days mortality in ACHBLF.

Key words: Acute-on-chronic hepatitis B liver failure, Systemic inflammatory response index, Prognosis, Risk factor, Blood cell counts related biomarkers

中图分类号:

R575.3

贾若曦,吕丽,刘涵云,吴寅平,李凤彩,赵泽华,王凯,范玉琛. 血细胞计数相关标志物对慢加急性乙型肝炎肝衰竭患者28天预后的诊断价值[J]. 山东大学学报 (医学版), 2025, 63(6): 89-99.

JIA Ruoxi, LYU Li, LIU Hanyun, WU Yinping, LI Fengcai, ZHAO Zehua, WANG Kai, FAN Yuchen. Diagnostic value of blood cell count-related biomarkers in predicting 28-day mortality in acute-on-chronic hepatitis b liver failure[J]. Journal of Shandong University (Health Sciences), 2025, 63(6): 89-99.

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