前白蛋白与总胆红素比值对HBV相关慢加急性肝衰竭患者短期预后的预测价值

李文娟 ,  赵卫峰 ,  黄小平

临床肝胆病杂志 ›› 2025, Vol. 41 ›› Issue (11) : 2272 -2277.

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临床肝胆病杂志 ›› 2025, Vol. 41 ›› Issue (11) : 2272 -2277. DOI: 10.12449/JCH251112
病毒性肝炎

前白蛋白与总胆红素比值对HBV相关慢加急性肝衰竭患者短期预后的预测价值

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Value of prealbumin-to-total bilirubin ratio in predicting the short-term prognosis of patients with HBV-related acute-on-chronic liver failure

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摘要

目的 评估入院时前白蛋白与总胆红素比值(PA/TBil)对HBV相关慢加急性肝衰竭(HBV-ACLF)患者90天死亡或肝移植的预测价值,并分析其与MELD评分联合后对短期预后预测效能的影响。 方法 回顾性分析2020年4月—2025年5月苏州大学附属第一医院感染病科收住入院的216例HBV-ACLF患者的临床资料,对患者随访3个月,根据结局将患者分为生存组(n=104)和死亡/移植组(n=112)。采用Kolmogorov-Smirnov检验分析计量资料是否符合正态分布,符合正态分布的计量资料两组间比较采用成组t检验,偏态资料两组间比较采用Mann-Whitney U检验;计数资料两组间比较采用χ2检验;采用单因素及多因素二元Logistic回归分析影响预后的因素;采用受试者操作特征曲线分析各指标对ACLF预后的预测效能,计算曲线下面积(AUC),并使用Delong检验对AUC进行比较。 结果 216例患者90天生存率为48.15%(104/216),生存组PLT、淋巴细胞计数、Alb、PA/TBil水平均显著高于死亡/移植组(P值均<0.05);年龄、WBC、中性粒细胞计数、PT、国际标准化比值、AST、TBil、肌酐、MELD评分均显著低于死亡/移植组(P值均<0.05)。多因素Logistic回归分析显示,年龄(OR=1.05,95%CI:1.02~1.09,P<0.001)、PA/TBil(OR=0.16,95%CI:0.05~0.46,P<0.001)、MELD评分(OR=1.09,95%CI:1.01~1.17,P=0.024)是HBV-ACLF患者90天预后的独立影响因素。PA/TBil、MELD评分及二者联合预测HBV-ACLF患者预后的AUC分别为0.760、0.779、0.811;PA/TBil联合MELD评分预测的AUC优于单一指标AUC(Z值分别为-2.058、2.017,P值均<0.05)。 结论 血清PA/TBil、MELD评分均可以有效预测HBV-ACLF患者的预后,二者联合对患者的预后预测效果明显优于单独使用MELD评分,这为临床风险分层管理和及时干预提供了重要参考。

Abstract

Objective To investigate the value of prealbumin-to-total bilirubin (PA/TBil) ratio on admission in predicting 90-day mortality or liver transplantation in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF), as well as the effect of its combination with Model for End-Stage Liver Disease (MELD) score on the predictive performance for short-term prognosis. Methods A retrospective analysis was performed for the clinical data of 216 HBV-ACLF patients who were admitted to Department of Infectious Diseases in the First Affiliated Hospital of Soochow University from April 2020 to May 2025, and the patients were followed up for 3 months. According to the outcome, the patients were divided into survival group with 104 patients and death/transplantation group with 112 patients. The Kolmogorov-Smirnov test was used to check whether the continuous data was in accordance with the normal distribution; the two-independent-samples t test was used for comparison of normally distributed continuous data between two groups, while the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups. The chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate binary Logistic regression analyses were used to investigate the influencing factors for prognosis, and the receiver operating characteristic (ROC) curve was used to analyze the performance of each indicator in predicting the prognosis of ACLF. The area under the ROC curve (AUC) was calculated, and the Delong test was used for comparison of AUC. Results A total of 216 patients were enrolled in this study, with a 90-day survival rate of 48.15% (104/216). Compared with the death/transplantation group, the survival group had significantly higher platelet count, lymphocyte count, albumin, and PA/TBil ratio (all P<0.05) and significantly lower age, white blood cell count, neutrophil count, prothrombin time, international normalized ratio, aspartate aminotransferase, total bilirubin, creatinine, and MELD score (all P<0.05). The multivariate Logistic regression analysis showed that age (odds ratio [OR]=1.05, 95% confidence interval [CI]: 1.02 — 1.09, P<0.001), PA/TBil ratio (OR=0.16, 95%CI: 0.05 — 0.46, P<0.001), and MELD score (OR=1.09, 95%CI: 1.01 — 1.17, P=0.024) were independent influencing factors for 90-day prognosis in HBV-ACLF patients. PA/TBil ratio and MELD score used alone or in combination had an AUC of 0.760, 0.779, and 0.811, respectively, in predicting the prognosis of HBV-ACLF patients, and PA/TBil ratio combined with MELD score had a better AUC than PA/TBil ratio or MELD score used alone (Z=-2.058 and 2.017, both P<0.05). Conclusion Both serum PA/TBil ratio and MELD score can effectively predict the prognosis of patients with HBV-ACLF, and a combination of the two indicators had a better predictive performance than MELD score alone, which provides an important reference for clinical risk stratification management and timely intervention.

Graphical abstract

关键词

乙型肝炎病毒 / 慢加急性肝功能衰竭 / 预后 / 前白蛋白 / 胆红素 / MELD评分

Key words

Hepatitis B Virus / Acute-on-Chronic Liver Failure / Prognosis / Prealbumin / Bilirubin / MELD Score

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李文娟,赵卫峰,黄小平. 前白蛋白与总胆红素比值对HBV相关慢加急性肝衰竭患者短期预后的预测价值[J]. 临床肝胆病杂志, 2025, 41(11): 2272-2277 DOI:10.12449/JCH251112

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慢加急性肝衰竭(ACLF)是一种发生于慢性肝病基础上的急性肝功能失代偿,可导致多器官功能衰竭,病情进展迅速,短期内病死率高达50%~90%1-4。因此,准确预测患者预后对于优化治疗策略、改善临床治疗效果具有重要意义5。目前临床常用的预后评估模型主要是Child-Pugh评分6、终末期肝病模型(model for end-stage liver disease,MELD)评分7、白蛋白-胆红素(albumin bilirubin,ALBI)分期模型8,然而,上述模型预测准确性有限,因此需要更准确、更易应用的HBV相关ACLF(HBV-ACLF)预后指标和模型。前白蛋白(PA)也称为转甲状腺素运载蛋白,主要由肝脏合成9,是评估肝脏疾病严重程度的敏感生物标志物10,已被证明是预测肝衰竭的独立预后指标11-12。有研究表明,总胆红素(TBil)是判断HBV-ACLF患者短期预后的独立危险因素13。故本研究探讨PA/TBil联合MELD评分对HBV-ACLF患者短期预后的预测价值,以期指导临床治疗。

1 资料与方法

1.1 研究对象

回顾性分析2020年4月—2025年5月本院感染病科收住入院的HBV-ACLF患者的临床资料,所有患者均接受积极治疗。纳入标准:入选患者均符合《肝衰竭诊治指南(2018年版)》14中关于HBV-ACLF的诊断标准。排除标准:(1)妊娠或哺乳期妇女;(2)合并其他肝炎病毒感染;(3)合并免疫性、酒精性、遗传代谢性、药物性、寄生虫性肝病;(4)合并HIV感染、恶性肿瘤、血液系统疾病的患者;(5)缺失随访资料者;(6)年龄<18岁者。

1.2 研究方法

收集HBV-ACLF患者姓名、年龄、性别、病因、既往史等基本信息资料,所有对象均于入院后24 h内抽取清晨空腹静脉血。检测实验室指标包括:血常规、肝肾功能等生化指标及凝血指标,观察患者肝性脑病、腹水、消化道出血等并发症情况,记录患者肝硬化相关并发症15。计算PA/TBil比值、MELD评分;MELD评分=3.78×ln[TBil(mg/dL)]+9.57×ln[Cr(mg/dL)]+11.2×ln [国际标准化比值(INR)]+6.43×病因,其中病因为胆汁性或酒精性时赋值为0,其他赋值为1,本研究对象均为HBV相关,故赋值均为116。通过电话随访形式获得患者出院后90天内的生存状况。

1.3 统计学方法

采用SPSS 27.0和GraphPad 10.1.2统计软件进行数据分析。采用Kolmogorov-Smirnov检验分析计量资料是否符合正态分布,符合正态分布的计量资料以x¯±s表示,两组间比较采用成组t检验;偏态资料以MP25P75)表示,两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ2检验。采用单因素及多因素二元Logistic回归分析影响预后的因素;采用受试者操作特征曲线(ROC曲线)分析各指标对ACLF预后的预测效能,并计算曲线下面积(AUC),使用Delong检验对AUC进行比较,利用约登指数寻找最佳截点。P<0.05为差异有统计学意义。

2 结果

2.1 一般资料

共纳入HBV-ACLF患者216例,其中男 174例(80.56%),女42例(19.44%),中位年龄55 (49~64)岁。根据患者生存状况分为生存组(n=104)与死亡/移植组(n=112)。两组间年龄、淋巴细胞计数、中性粒细胞计数、WBC、PLT、PT、INR、AST、TBil、Alb、PA/TBil、Cr、MELD评分比较,差异均有统计学意义(P值均<0.05)(表1)。

2.2 HBV-ACLF患者预后影响因素的Logistic回归分析

将单因素分析有统计学意义(P<0.05)的临床指标纳入多因素分析,在排除指标之间共线性及校正后,进行多因素Logistic回归分析,筛选出年龄、MELD评分、PA/TBil为HBV-ACLF患者90天预后的独立影响因素(P值均<0.05)(表2)。

2.3 MELD评分和PA/TBil对HBV-ACLF患者90天预后的预测价值

ROC曲线显示,PA/TBil、MELD评分以及二者联合对HBV-ACLF患者的短期预后均有预测价值(P值均<0.001),其AUC分别为0.760、0.779、0.811(图1表3)。PA/TBil与MELD评分的AUC相比,差异无统计学意义(Z=-0.554,P>0.05)。PA/TBil、MELD评分的AUC明显低于二者联合,差异均有统计学意义(Z值分别为-2.058、2.017,P值均<0.05),表明PA/TBil联合MELD评分可以提高预测效能。

3 讨论

HBV-ACLF是我国常见的肝衰竭类型,病死率较高。肝移植是提高HBV-ACLF患者生存率的主要手段17-18,但费用高昂,普通患者难以负担,因此早期识别并及时治疗是改善预后的关键。PA/TBil作为一种简便、经济且易于重复检测的指标,在预测肝衰竭的病情进展和短期预后方面显示出良好的潜力19。根据本研究结果,PA/TBil比值、MELD评分及二者联合均能有效预测HBV-ACLF患者的短期预后(P值均<0.001),二者联合模型对HBV-ACLF患者预后的预测效能(AUC=0.811),显著优于单一指标,提示其预测能力更强。

目前,传统的肝功能评分系统如Child-Pugh评分、MELD评分、ALBI评分虽广泛应用于临床,但均存在一定的局限性。Child-Pugh评分常用来评估患者的肝功能和肝损伤情况,但该评分系统存在一定的主观性和滞后性,难以准确、实时地反映患者当前的肝脏储备功能和损伤程度,在快速变化的临床情境中可能会延误最佳治疗时机20-21。MELD评分作为评估肝功能障碍的经典模型,最初用于预测慢性肝病(如终末期肝病)患者在器官移植等治疗前的中短期死亡风险22。ACLF病程的急性特征决定了患者的预后受到多因素的复杂影响,如炎症标志物的动态变化、器官衰竭的数量和严重程度等23。MELD评分虽然能够较好地反映患者的部分生理损伤,但其未能充分考量急性炎症反应、肝外器官衰竭(如心、肺、脑)以及一些其他病理机制(如PA、胆汁淤积标志物)的影响24。因此,单纯依赖于MELD评分可能会低估部分患者的死亡风险。ALBI评分仅包含Alb和胆红素两项指标,但Alb水平极易受到外源性输注等人为因素的影响,评估预后可能存在偏倚25-26。为弥补不足,本研究将PA/TBil与MELD评分进行联合评估。既往研究发现,PA水平与肝衰竭预后密切相关10-12。血清PA由于半衰期短(约1.9天),对肝功能变化反应更为敏感,是评估肝脏合成功能及储备能力的重要指标。当PA的水平持续性下降时,往往提示预后不良,而治疗过程中PA水平的逐渐回升则提示肝脏再生修复能力良好。入院时PA水平可作为HBV-ACLF患者30天死亡的独立预测指标27。肝衰竭发生时,由于肝细胞严重变性、坏死、小叶结构重建,短时间内发生胆管梗阻,从而引起胆红素急剧升高。TBil是HBV-ACLF预后评估中最早出现异常、最易获得且最稳定的实验室指标之一,其水平与ACLF患者肝衰竭的危险性和严重程度成正比28,是反映肝功能和判断短期预后的常用实验室指标,也是死亡的独立危险因素,但其单项指标预测能力有限29。多中心证据表明,PA/TBil相较单纯PA或TBil具有更优的生存预测性能30,整体判别力更高。当肝脏合成功能受损时,PA水平降低;胆汁排泄受阻时,TBil水平升高。由于两项指标反映的病理过程不同且变化方向相反,构建PA/TBil比值能够在一定程度上增强对肝脏合成功能与胆汁淤积程度的综合反映,使其成为一个更敏感的复合指标。本研究中PA/TBil与MELD评分联合应用的模型,通过结合反映肝脏合成功能的PA与代表肝细胞损伤的TBil,更全面地评估了HBV-ACLF患者的肝功能储备和损伤状态,弥补了现有评分系统单一维度的不足。这与最新研究强调多维度评估ACLF预后的趋势相符31-32,值得在临床实践中推广应用。

综上所述,PA/TBil和MELD评分均可预测HBV-ACLF患者的预后,且相较于单一指标,联合使用可更准确地预测患者预后情况,有助于及早识别高风险患者。同时PA/TBil比值计算简便,基于常规血液生化检测即可快速获得,简便易行、成本较低、可重复性好,还可连续动态监测,便于及时掌握患者病情变化,具有潜在的临床应用价值,特别是在资源有限的医疗环境中,PA/TBil可能成为一种实用的替代指标。本研究也存在一定的局限性:首先,作为一项单中心回顾性研究,例数有限,无法完全排除偏倚及某些未测量混杂因素的影响,应进一步开展多中心研究验证;其次,本研究仅针对因HBV感染所致ACLF住院的患者进行分析,结论可能无法外推至其他病因人群;最后,本研究未监测肝衰竭的病程转归及其他预后相关指标的动态变化,有待进一步的前瞻性临床研究予以探讨。

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基金资助

“十三五”国家科技重大专项(2017ZX10203201002-002)

中国肝炎防治基金会专项(TGQB20180371)

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