血浆置换与双重血浆分子吸附系统单用或联合使用治疗HBV相关慢加急性肝衰竭患者预后预测模型的建立与评估

黄贝贝; 宁玲; 李文渊; 郑晓玮; 张玥; 江守伟; 张振华; 李磊

doi:10.3969/j.issn.1001-5256.2021.12.015

血浆置换与双重血浆分子吸附系统单用或联合使用治疗HBV相关慢加急性肝衰竭患者预后预测模型的建立与评估

DOI: 10.3969/j.issn.1001-5256.2021.12.015

1.
安徽医科大学附属省立医院感染病科，合肥 230001
2.
安徽医科大学第二附属医院感染和肝病科，合肥 230601

基金项目:

安徽省自然科学基金资助项目 (1208085QH147);

北京肝胆相照公益基金会人工肝专项基金课题 (RGGJJ-2021-002)

详细信息

通信作者:
李磊，lilei0403@163.com

中图分类号: R575.3
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出版历程
- 收稿日期: 2021-07-14
- 录用日期: 2021-08-16
- 出版日期: 2021-12-20

Establishment of a predictive model for the prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure treated with plasma exchange and double plasma molecular adsorption system alone or in combination

1.
Department of Infectious Diseases, The Affiliated Provincial Hospital of Anhui Medical University, Hefei 230001, China
2.
Department of Infectious and Liver Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China

Research funding:

Natural Science Foundation of Anhui Province (1208085QH147);

Artificial liver support system Special Fund project of Beijing Hepatology Charity Foundation (RGGJJ-2021-002)

摘要

摘要: 目的观察采用血浆置换(PE)与双重血浆分子吸附系统(DPMAS)单用或联合使用(PE+DPMAS)治疗的HBV感染相关慢加急性肝衰竭(HBV-ACLF)患者的24周生存情况，建立评估患者24周预后的预测模型。方法收集2015年1月—2019年12月在安徽医科大学附属省立医院行PE+DPMAS治疗的133例HBV-ACLF患者的临床资料，根据治疗后24周随访生存情况分为生存组(n=71)和死亡组(n=62)。另收集2018年1月—2020年1月在安徽医科大学第二附属医院接受PE+DPMAS治疗的55例HBV-ACLF患者为验证组验证模型效能。收集临床资料包括采用人工肝治疗的模式、性别、年龄、TBil、INR、肌酐(Cr)、血清钠、PLT、Alb，是否有腹水、肝肾综合征、肝性脑病和消化道出血。正态分布的计量资料2组间比较采用t检验，偏态分布的计量资料2组间比较采用Wilcoxon秩和检验; 计数资料组间比较采用χ²检验和Fisher检验；PE+DPMAS治疗的HBV-ACLF患者预后因素分析采用Cox回归分析法，并建立预测模型；绘制受试者工作特征曲线(ROC曲线)，采用DeLong法比较新的预测模型与MELD及MELD-Na评分的ROC曲线下面积(AUC)。结果治疗后24周建模组共存活71例，死亡62例。Cox回归分析显示年龄(HR=1.030，P=0.013)、TBil(HR=1.018，P＜0.001)、INR(HR=1.517，P＜0.001)和PLT(HR=0.993，P=0.04)是患者24周生存的独立影响因素。根据Cox回归分析结果建立了行PE+DPMAS治疗的HBV-ACLF患者的预后模型(ATIP)=0.029×年龄(岁)+0.018×TBil(mg/dL)+0.417×INR-0.007×PLT(10⁹/L)。建模组和验证组均显示ATIP模型的预测效能优于MELD和MELD-Na评分(P值均＜0.05)。结论行PE+DPMAS治疗的HBV-ACLF患者的年龄、TBil、INR和PLT为24周生存的独立影响因素；ATIP模型对行PE+DPMAS治疗的HBV-ACLF患者的24周预后预测效能良好。
- 肝功能衰竭 /
- 乙型肝炎病毒 /
- 肝, 人工 /
- 预后
Abstract: Objective To observe the 24-week survival status of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) treated with plasma exchange (PE) and double plasma molecular adsorption system (DPMAS) alone or in combination, and to establish a predictive model for 24-week prognosis. Methods Related clinical data were collected from 133 patients with HBV-ACLF who received PE and DPMAS alone or in combination in The Affiliated Provincial Hospital of Anhui Medical University from January 2015 to December 2019, and according to the survival status at the 24-week follow-up after treatment, they were divided into survival group with 71 patients and death group with 62 patients. A total of 55 patients with HBV-ACLF who received PE and DPMAS alone or in combination in The Second Affiliated Hospital of Anhui Medical University from January 2018 to January 2020 were enrolled as validation group to validate the performance of the model. Related clinical data included mode of artificial liver support therapy, age, sex, total bilirubin (TBil), international normalized ratio (INR), creatinine (Cr), serum sodium, platelet count (PLT), albumin (Alb), and presence or absence of ascites, hepatorenal syndrome, hepatic encephalopathy, and gastrointestinal bleeding. The t-test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon rank-sum test was used for comparison of continuous data with skewed distribution between two groups; the chi-square test and the Fisher's exact test were used for comparison of categorical data between groups. The Cox regression model was used to analyze the influencing factors for the prognosis of HBV-ACLF patients after PE and DPMAS alone or in combination and establish a predictive model; the receiver operator characteristic (ROC) curve was plotted and the DeLong method was used to compare the area under the ROC curve (AUC) between the new predictive model and Model for End-Stage Liver Disease (MELD)/MELD combined with serum sodium concentration (MELD-Na) scores. Results At 24 weeks after treatment, 71 patients survived and 62 patients died in the modeling group. The Cox regression analysis showed age (hazard ratio [HR]=1.030, P=0.013), TBil (HR=1.018, P < 0.001), INR (HR=1.517, P < 0.001), and PLT (HR=0.993, P=0.04) were independent influencing factors for 24-week survival. According to the results of the Cox regression analysis, a prognostic model for HBV-ACLF patients treated with PE and DPMAS alone or in combination was established as ATIP=0.029×age (years)+0.018×TBil (mg/dL)+0.417×INR-0.007×PLT (10⁹/L). Both the modeling group and the validation group showed that the ATIP model had a better predictive performance than MELD and MELD-NA scores(all P < 0.05). Conclusion Age, TBil, INR, and PLT are independent influencing factors for the 24-week survival of HBV-ACLF patients treated with PE and DPMAS alone or in combination, and the ATIP model has a good performance in predicting the 24-week prognosis of HBV-ACLF patients treated with PE and DPMAS alone or in combination.
- Liver Failure /
- Hepatitis B virus /
- Liver, Artificial /
- Prognosis

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图 1 不同预后模型预测HBV-ACLF患者24周生存的ROC曲线

注：a，模型组；b，验证组。

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表 1 建模组和验证组患者一般资料比较

指标	建模组(n=133)	验证组(n=55)	统计值	P值
年龄(岁)	47.89±11.98	51.15±14.83	t=1.575	0.153
女/男(例)	17/116	11/44	χ²=1.081	0.746
腹水[例(%)]	85(63.91)	31(56.36)	χ²=0.645	0.422
肝肾综合征[例(%)]	21(15.79)	11(20.00)	χ²=0.236	0.627
肝性脑病[例(%)]	28(21.05)	8(14.55)	χ²=0.685	0.408
消化道出血[例(%)]	9(6.77)	1(1.82)		0.286
TBil(mg/dL)	23.88(18.92~27.44)	21.8(15.79~26.56)	Z=-1.791	0.073
INR	2.18(1.66~2.72)	1.64(1.51~2.21)	Z=-3.20	0.001
Alb(g/dL)	32.0(29.3~34.7)	32.6(29.8~36.5)	Z=-1.416	0.157
Na(mmol/L)	136(134~139)	137(133~138)	Z=-0.983	0.326
Cr(mg/dL)	0.78(0.66~0.96)	0.61(0.48~0.77)	Z=-4.158	＜0.001
PLT(10⁹/L)	89(59~119)	106(56~181)	Z=-1.513	0.131
MELD	24.67(21.00~29.36)	19.23(16.23~26.00)	Z=-4.061	＜0.001
MELD-Na	25.66(22.14~31.93)	21.03(16.75~28.16)	Z=-3.042	0.002
ALSS模式[例(%)]			χ²=1.600	0.449
PE	45(33.83)	21(38.18)
DPMAS	39(29.32)	19(34.55)
PE+DPMAS	49(36.84)	15(23.27)

下载: 导出CSV

表 2 建模组患者24周生存预后的单因素和多因素Cox回归分析

参数	单因素Cox回归分析				多因素Cox回归分析
参数	B值	SE	HR(95%CI)	P值	B值	SE	HR(95%CI)	P值
年龄	0.044	0.010	1.045(1.025~1.065)	＜0.001	0.029	0.012	1.030(1.006~1.054)	0.013
性别	-0.201	0.401	0.818(0.372~1.795)	0.616
腹水	0.468	0.285	1.597(0.914~2.792)	0.100
肝肾综合征	0.814	0.291	2.257(1.276~3.995)	0.005
肝性脑病	0.833	0.273	2.301(1.348~3.928)	0.002
消化道出血	1.011	0.381	2.749(1.304~5.795)	0.008
TBil	0.017	0.005	1.017(1.007~1.026)	0.001	0.018	0.005	1.018(1.008~1.028)	＜0.001
INR	0.435	0.079	1.546(1.323~1.807)	＜0.001	0.417	0.109	1.517(1.226~1.877)	＜0.001
Alb	-0.043	0.020	0.958(0.920~0.997)	0.035
Na	-0.050	0.026	0.952(0.940~1.001)	0.057
Cr	0.765	0.316	2.149(1.157~3.991)	0.015
PLT	-0.010	0.003	0.990(0.984~0.996)	0.002	-0.007	0.004	0.993(0.986~1.000)	0.040
ALSS模式
PE
DPMAS	0.25653	0.31632	1.292(0.695~2.402)	0.417
PE+DPMAS	0.05008	0.30897	1.051(0.574~1.926)	0.871

下载: 导出CSV

表 3 行PE+DPMAS治疗的HBV-ACLF患者预后评分系统预测价值比较

模型	建模组					验证组
模型	灵敏度(%)	特异度(%)	cut off值	AUC	95% CI	AUC	95% CI
ATIP	67.74	94.37	0.31	0.863	0.800~0.926	0.768	0.636~0.899
MELD	69.35	81.69	25.55	0.777¹⁾	0.695~0.858	0.712¹⁾	0.575~0.850
MELD-Na	77.42	67.61	25.22	0.768¹⁾	0.688~0.849	0.691¹⁾	0.545~0.837
注：与ATIP比较，1) P＜0.05。

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