IL-6联合终末期肝病模型评分对HBV相关慢加急性肝衰竭预后的预测价值

王艳; 徐英; 孙蔚; 陈丽; 甘建和; 顾静

doi:10.3969/j.issn.1001-5256.2022.08.011

IL-6联合终末期肝病模型评分对HBV相关慢加急性肝衰竭预后的预测价值

DOI: 10.3969/j.issn.1001-5256.2022.08.011

苏州大学附属第一医院感染科，江苏苏州 215006

基金项目:

国家科技部“十三五”重大专项 (2017ZX10203201002-002);

苏州市“科教兴卫”青年科技项目 (KJXW2020003)

伦理学声明：本研究经由苏州大学附属第一医院伦理委员会审批通过，批号：(2021)伦研批第135号。所有患者均签署知情同意书。

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突，特此声明。

作者贡献声明：王艳负责课题设计，资料分析，撰写论文；徐英、孙蔚、陈丽参与收集数据，修改论文；顾静负责拟定写作思路，指导撰写文章并最后定稿；甘建和负责指导写作思路。

详细信息

通信作者:
顾静, 296326823@qq.com

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出版历程
- 收稿日期: 2021-10-21
- 录用日期: 2021-12-06
- 出版日期: 2022-08-20

Value of interleukin-6 combined with Model for End-Stage Liver Disease score in predicting the prognosis of hepatitis B virus-related acute-on-chronic liver failure

Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China

Research funding:

the National S & T Major Project （2017ZX10203201002-002）

Suzhou Youth Science and Technology Fund （KJXW2020003）

More Information

Corresponding author: GU Jing, 296326823@qq.com(ORCID: 0000-0002-7904-2793)

摘要

摘要: 目的探讨IL-6联合终末期肝病模型(MELD)评分对HBV相关慢加急性肝衰竭(HBV-ACLF)患者预后的预测价值。方法选取2015年1月—2018年12月于苏州大学附属第一医院住院的86例HBV-ACLF患者，根据随访90 d的生存情况分为死亡组(n=50)和存活组(n=36)。采用ELISA法测定血清IL-6水平，统计患者的一般资料。符合正态分布的计量资料两组间比较采用t检验，不符合正态分布的计量资料两组间比较采用Mann-Whitney U检验；分类计数资料两组间比较采用χ²检验。IL-6与其他变量行Pearson相关性分析，采用二元logistic回归分析影响HBV-ACLF患者预后的独立危险因素，利用ROC曲线评价IL-6联合MELD评分对HBV-ACLF预后的预测价值。结果死亡组与存活组红细胞比积(Hct)(t=2.413)、PLT(t=6.584)、TBil(t=-8.070)、PT(U=77.500)、国际标准化比值(INR)(U=102.000)、HBV DNA(t=-2.767)、IL-6(t=-16.543)、MELD评分(t=-8.192)组间差异有统计学意义(P值均＜0.05)；死亡组IL-6水平高于存活组[(27.13±12.18) pg/mL vs (9.72±5.56) pg/mL，P < 0.001]。Pearson相关性分析结果显示，IL-6与TBil、PT呈显著正相关(r值分别为0.579、0.681，P值均＜0.001)。运用二元logistic回归分析结果显示，IL-6(OR=1.480，95%CI：1.196~1.833，P=0.007)、MELD评分(OR=1.128，95%CI：1.033~1.231，P < 0.001)是HBV-ACLF患者90 d死亡的独立预测因子。IL-6联合MELD评分模型的AUC(AUC=0.891，95%CI: 0.778~0.999)高于IL-6(AUC=0.838，95%CI: 0.687~0.989)、MELD评分(AUC=0.783，95%CI: 0.634~0.933)。IL-6联合MELD评分模型对HBV-ACLF预后的预测价值高于IL-6(Z=-2.257，P=0.024)。结论 IL-6联合MELD评分模型可作为评估HBV-ACLF患者短期预后较好的预测模型。
- 乙型肝炎病毒 /
- 慢加急性肝功能衰竭 /
- 预后
Abstract: Objective To investigate the value of interleukin-6 (IL-6) combined with Model for End-stage Liver Disease (MELD) score in predicting the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). Methods A total of 86 patients with HBV-ACLF who were hospitalized in The First Affiliated Hospital of Soochow University from January 2015 to December 2018 were enrolled, and according to their survival status after follow-up for 90 days, they were divided into death group with 50 patients and survival group with 36 patients. ELISA was used to measure the serum level of IL-6, and a statistical analysis was performed for general information. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Pearson correlation analysis was performed for IL-6 and other variables; a binary logistic regression analysis was used to investigate the independent risk factors for the prognosis of patients with HBV-ACLF; the receiver operating characteristic (ROC) curve was used to assess the value of IL-6 combined with MELD score in predicting the prognosis of HBV-ACLF. Results There were significant differences between the death group and the survival group in hematocrit (t=2.413), platelet count (t=6.584), total bilirubin (TBil) (t=-8.070), prothrombin time (PT) (U=77.500), international standardized ratio (U=102.000), HBV DNA (t=-2.767), IL-6 (t=-16.543), and MELD score (t=-8.192), and the death group had a significantly higher level of IL-6 than the survival group (27.13±12.18 pg/mL vs 9.72±5.56 pg/mL, P < 0.001). The Pearson correlation analysis showed that IL-6 was positively correlated with TBil and PT (r=0.579 and 0.681, both P < 0.001). The binary logistic regression analysis showed that IL-6 (odds ratio[OR]=1.480, 95% confidence interval [CI]: 1.196~1.833, P=0.007) and MELD score (OR=1.128, 95%CI: 1.033~1.231, P < 0.001) were independent risk factors for the death of HBV-ACLF patients within 90 days. IL-6 combined with MELD score had an area under the ROC curve (AUC) of 0.891 (95%CI: 0.778~0.999), with a higher AUC than IL-6 (AUC=0.838, 95%CI: 0.687~0.989) or MELD score (AUC=0.783, 95%CI: 0.634~0.933). IL-6 combined with MELD score had a significantly higher value than IL-6 alone in predicting the prognosis of patients with HBV-ACLF (Z=-2.257, P=0.024). Conclusion IL-6 combined with MELD score can be used as a good model for predicting the short-term prognosis of patients with HBV-ACLF.
- Hepatitis B Virus /
- Acute-On-Chronic Liver Failure /
- Prognosis

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图 1 IL-6与TBil相关性分析

Figure 1. Correlation analysis of IL-6 and TBil

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图 2 IL-6与PT相关性分析

Figure 2. Correlation analysis of IL-6 and PT

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图 3 IL-6、MELD评分、IL-6联合MELD评分模型的ROC曲线

Figure 3. ROC curve of IL-6, MELD score and IL-6 combined MELD score model

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表 1 两组患者一般资料比较

Table 1. Comparison of general data between the two groups

指标	死亡组(n=50)	存活组(n=36)	统计值	P值
男性[例(%)]	32(64.00)	28(77.78)	χ²=0.624	0.498
年龄(岁)	50.76±11.26	53.52±12.36	t=0.427	0.649
WBC(×10⁹/L)	6.85±2.07	7.13±2.28	t=0.564	0.574
Hct(%)	0.38±0.06	0.41±0.07	t=2.413	0.018
PLT(×10⁹/L)	72.68±13.65	91.70±16.73	t=6.584	＜0.001
TBil(μmol/L)	344.70±37.58	282.63±50.08	t=-8.070	＜0.001
ALT(U/L)	629.51±146.54	577.34±113.26	t=-1.539	0.293
AST(U/L)	637.26±157.49	523.04±127.86	t=-3.457	0.346
Alb(g/L)	31.56±2.74	34.64±3.37	t=0.952	0.344
SCr(μmol/L)	76.35(69.65~88.78)	72.50(61.15~81.80)	U=601.500	0.349
PT(s)	31.80(25.15~33.10)	26.40(25.15~27.25)	U=77.500	＜0.001
INR	2.45(2.13~2.80)	1.70(1.60~1.85)	U=102.000	＜0.001
HBV DNA(×10⁷IU/mL)	2.54±0.59	2.39±0.59	t=-2.767	0.006
IL-6(pg/mL)	27.13±12.18	9.72±5.56	t=-16.543	＜0.001
MELD评分	27.15±3.48	22.54±2.85	t=-8.192	＜0.001

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表 2 HBV-ACLF患者预后相关因素分析

Table 2. Analysis of prognosis-associated factors in HBV-ACLF patients

指标	单因素分析			多因素分析
指标	OR	95%CI	P值	OR	95%CI	P值
年龄	0.994	0.955~1.035	0.774
性别	0.958	0.396~2.317	0.925
WBC	0.945	0.772~1.157	0.585
Hct	＜0.001	0~0.246	0.024	＜0.001	0~0.306	0.057
PLT	0.938	0.896~0.982	＜0.001	0.923	0.874~0.975	0.254
TBi	1.032	1.015~1.050	＜0.001	1.007	0.966~1.050	0.752
ALT	0.979	0.953~1.005	0.117
AST	1.021	0.994~1.049	0.128
Alb	0.921	0.784~1.081	0.314
SCr	0.976	0.940~1.013	0.201
PT	2.941	1.815~4.764	＜0.001		1.676~7.976	0.067
INR	740.685	40.543~13 531.609	＜0.001	737.956	39.347~15 051.320	0.493
HBV DNA	2.074	1.168~3.682	0.013	0.706	0.281~1.778	0.460
IL-6	1.150	1.066~1.240	＜0.001	1.480	1.196~1.833	0.007
MELD评分	1.584	1.311~1.915	0.001	1.128	1.033~1.231	＜0.001

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