国际标准化比值/血小板比值指数对原发性胆汁性胆管炎相关肝纤维化的诊断价值

乔芳芳; 孙长宇; 何佳倩; 董少雨; 张建营

doi:10.3969/j.issn.1001-5256.2022.03.012

国际标准化比值/血小板比值指数对原发性胆汁性胆管炎相关肝纤维化的诊断价值

DOI: 10.3969/j.issn.1001-5256.2022.03.012

1.
郑州大学第一附属医院感染科，郑州 450052
2.
郑州大学公共卫生学院，郑州 450001

基金项目:

国家科技重大专项子课题 (2018ZX10302205-004)

伦理学声明：本研究方案于2021年9月25日经由郑州大学第一附属医院伦理委员会审批，批号：KY-2021-00520。

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。

作者贡献声明：乔芳芳负责课题设计，资料分析，撰写论文；何佳倩、董少雨负责收集数据和统计分析；张建营负责指导数据统计分析；孙长宇负责指导撰写文章并最后定稿。

详细信息

通信作者:
孙长宇，changyu8188@163.com

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出版历程
- 收稿日期: 2021-07-13
- 录用日期: 2021-08-16
- 出版日期: 2022-03-20

Value of international normalized ratio-to-platelet ratio in the diagnosis of liver fibrosis in patients with primary biliary cholangitis

1.
Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
2.
School of Public Health, Zhengzhou University, Zhengzhou 450001, China

Research funding:

Sub-project of the National Science and Technology Major Project (2018ZX10302205-004)

More Information

Corresponding author: SUN Changyu, changyu8188@163.com(ORCID:0000-0001-9993-8098)

摘要

摘要: 目的探究国际标准化比值/PLT比值指数(INPR)对原发性胆汁性胆管炎(PBC)患者肝纤维化程度的诊断价值，并与AST/PLT比值指数(ARRI)和肝纤维化4因子指数(FIB- 4)进行比较。方法回顾性纳入2013年10月—2021年3月在郑州大学第一附属医院行肝穿刺活检明确诊断为PBC的患者。采用Scheuer评分系统评估肝纤维化程度，分为S0~S4期。根据肝穿刺病理结果将患者的肝纤维化程度分为显著肝纤维化(≥S2)、进展期肝纤维化(≥S3)和肝硬化(S4)。收集患者一般资料、肝功能、血常规、血凝等指标，利用公式计算血清学无创模型INPR、APRI及FIB-4。计量资料多组间比较采用Kruskal-Wallis H秩和检验；计数资料多组间比较采用χ²检验。采用Spearman相关分析评估无创模型与肝纤维化分期的相关性，应用受试者工作特征曲线(ROC曲线)评估血清学无创模型对肝纤维化程度的诊断效能，ROC曲线下面积(AUC)的比较采用DeLong法。结果共纳入143例PBC患者，其中肝纤维化S0、S1、S2、S3和S4期分别为4、50、46、26和17例。INPR评分在不同肝纤维化程度PBC患者间差异显著(χ²=27.347，P＜0.001)。随着肝纤维化程度加重，INPR评分逐渐升高，INPR与肝纤维化程度呈正相关(r=0.419，P＜0.01)。ROC曲线分析显示，INPR、APRI、FIB-4用于诊断PBC显著肝纤维化(≥S2)的AUC分别为0.691、0.706、0.742，对应的cut-off值分别为0.63、0.59、2.68。INPR、APRI、FIB-4用于诊断PBC进展期肝纤维化(≥S3)的AUC分别为0.731、0.675、0.756，对应的cut-off值分别为0.64、1.23、4.63。INPR、APRI、FIB-4用于诊断PBC肝硬化(S4)的AUC分别为0.820、0.786、0.818，对应的cut-off值分别为0.95、1.26、4.63。在评估显著肝纤维化、进展期肝纤维化和肝硬化方面，INPR的AUC与APRI和FIB-4比较，差异均无统计学意义(P值均＞0.05)。结论 INPR是一种简单、准确的肝纤维化无创评估模型，对PBC肝纤维化有一定的诊断价值。
- 肝硬化 /
- 胆管炎 /
- 诊断
Abstract: Objective To investigate the value of international standardized ratio-to-platelet ratio (INPR) versus aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) in the diagnosis of liver fibrosis in patients with primary cholangitis (PBC). Methods A retrospective analysis was performed for the patients who underwent liver biopsy and were diagnosed with PBC in The First Affiliated Hospital of Zhengzhou University from October 2013 to March 2021. Scheuer score was used to systematically evaluate the degree of liver fibrosis (S0-S4 stage). According to the results of liver biopsy, the degree of liver fibrosis was classified as significant liver fibrosis (≥S2), progressive liver fibrosis (≥S3), and liver cirrhosis (S4). Related data including general information, liver function, routine blood test results, and blood coagulation were collected, and related formulas were used to calculate the values of the noninvasive serological models INPR, APRI, and FIB-4. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the chi-square test was used for comparison of categorical data between multiple groups. A Spearman correlation analysis was used to evaluate the correlation between noninvasive models and liver fibrosis stage. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the noninvasive serological models in the diagnosis of liver fibrosis degree, and the DeLong method was used for comparison of the area under the ROC curve (AUC). Results A total of 143 patients with PBC were enrolled in the study, among whom 4 had stage S0 liver fibrosis, 50 had stage S1 liver fibrosis, 46 had stage S2 liver fibrosis, 26 had stage S3 liver fibrosis, and 17 had stage S4 liver fibrosis. There was a significant difference in INPR value between the PBC patients with different liver fibrosis degrees (χ²=27.347, P < 0.001). INPR value gradually increased with the aggravation of liver fibrosis degree, and INPR was positively correlated with liver fibrosis degree (r=0.419, P < 0.01). The ROC curve analysis showed that INPR, APRI, and FIB-4 had an AUC of 0.691, 0.706, and 0.742, respectively, in the diagnosis of significant liver fibrosis (≥S2) in PBC patients, at the corresponding cut-off values of 0.63, 0.59, and 2.68, respectively. INPR, APRI, and FIB-4 had an AUC of 0.731, 0.675, and 0.756, respectively, in the diagnosis of progressive hepatic fibrosis (≥S3) in PBC patients, at the corresponding cut-off values of 0.64, 1.23, and 4.63, respectively. INPR, APRI, and FIB-4 had an AUC of 0.820, 0.786, and 0.818, respectively, in the diagnosis of liver cirrhosis (S4) in PBC patients, at the corresponding cut-off values of 0.95, 1.26, and 4.63, respectively. In the evaluation of significant liver fibrosis, progressive liver fibrosis, and liver cirrhosis, there was no significant difference in AUC between INPR and APRI/FIB-4 (all P > 0.05). Conclusion INPR is a simple and accurate noninvasive model for the evaluation of liver fibrosis and has a certain value in the diagnosis of liver fibrosis in PBC.
- Liver Cirrhosis /
- Cholangitis /
- Diagnosis

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图 1 INPR、APRI、FIB-4诊断不同肝纤维化分期的ROC曲线

注：a，显著肝纤维化；b，进展期肝纤维化；c，肝硬化。

下载: 全尺寸图片幻灯片

表 1 不同肝纤维化分期患者的临床资料比较

指标	S0(n=4)	S1(n=50)	S2(n=46)	S3(n=26)	S4(n=17)	χ²值	P值
男/女(例)	0/4	6/44	7/39	1/25	1/16	2.485	0.640
年龄(岁)	54.0(49.3~64.8)	55.0(44.8~62.0)	52.0(47.0~63.0)	60.5(50.3~65.0)	54.0(49.5~65.5)	4.761	0.313
INPR	0.39(0.33~1.02)	0.52(0.43~0.69)	0.64(0.46~1.02)	0.81(0.63~1.18)²⁾	1.39(0.81~1.78)¹⁾²⁾³⁾	27.347	＜0.001
APRI	0.34(0.20~0.71)	0.64(0.37~1.32)	1.06(0.69~2.50)	1.30(0.72~1.71)	2.19(1.28~3.81)¹⁾²⁾	23.942	＜0.001
FIB-4	1.40(1.02~2.36)	2.02(1.19~3.76)	3.09(1.88~5.19)	5.00(2.48~6.01)²⁾	7.89(4.98~10.30)¹⁾²⁾³⁾	34.211	＜0.001
INR	0.96(0.90~1.02)	0.95(0.90~1.00)	0.99(0.94~1.04)	0.96(0.91~1.04)	1.11(0.96~1.22)	15.843	0.003
PLT(×10⁹/L)	248.0(121.3~289.3)	172.0(145.3~225.0)	158.0(102.5~223.0)	116.0(85.8~156.5)	88.0(67.5~107.5)	24.518	＜0.001
ALT(U/L)	29.0(21.3~38.3)	46.5(24.0~91.0)	59.0(35.8~101.2)	39.5(23.2~62.0)	63.0(29.5~96.0)	7.308	0.120
AST(U/L)	24.0(23.0~40.0)	45.5(24.0~70.5)	61.5(34.5~114.2)	55.5(33.0~70.2)	69.0(38.0~110.5)	13.626	0.009
GGT(U/L)	102.5(46.8~418.5)	140.5(47.5~311.5)	163.5(76.5~379.3)	243.0(115.5~386.8)	178.0(78.0~261.5)	4.826	0.306
ALP(U/L)	151.5(77.0~229.0)	151.0(97.5~232.8)	223.0(121.8~359.5)	229.0(103.0~315.3)	202.0(152.0~371.0)	7.420	0.115
Alb(g/L)	43.6(40.5~46.7)	39.8(38.5~42.3)	38.5(34.6~41.3)	38.4(34.3~42.4)	34.6(29.5~38.7)	21.543	＜0.001
RDW(%)	13.5(12.8~14.7)	13.5(12.7~15.0)	14.5(13.3~16.1)	14.2(13.6~16.8)	16.5(14.9~16.8)	20.972	＜0.001
TBil(μmol/L)	12.4(10.6~13.7)	10.7(7.7~18.0)	12.9(9.1~34.2)	15.3(12.3~19.2)	25.0(12.9~70.1)	13.120	0.011
DBil(μmol/L)	5.5(4.2~7.7)	5.0(3.5~9.0)	7.0(4.8~29.9)	9.1(5.9~13.2)	14.4(7.2~50.1)	14.498	0.006
IBil(μmol/L)	6.4(5.7~7.2)	4.9(3.5~8.0)	5.4(4.1~7.0)	5.6(4.2~7.0)	6.2(4.8~9.0)	5.126	0.275
注：与S0分期比较，1)P＜0.05；与S1分期比较，2)P＜0.05；与S2分期比较，3)P＜0.05。

下载: 导出CSV

表 2 INPR、APRI及FIB-4对PBC显著肝纤维化的诊断价值

指标	AUC	P值	95%CI	cut-off值	敏感度(%)	特异度(%)	准确度(%)
INPR	0.691	＜0.001	0.609~0.766	0.63	67.42	68.52	67.80
APRI	0.706	＜0.001	0.625~0.780	0.59	82.02	51.85	70.60
FIB-4	0.742	＜0.001	0.662~0.811	2.68	69.66	70.37	69.20

下载: 导出CSV

表 3 INPR、APRI及FIB-4对PBC进展期肝纤维化的诊断价值

指标	AUC	P值	95%CI	cut-off值	敏感度(%)	特异度(%)	准确度(%)
INPR	0.731	＜0.001	0.650~0.801	0.64	84.09	62.63	69.90
APRI	0.675	0.0003	0.591~0.751	1.23	65.91	67.68	66.40
FIB-4	0.756	＜0.001	0.677~0.824	4.63	68.18	81.82	76.90

下载: 导出CSV

表 4 INPR、APRI及FIB-4对PBC肝硬化的诊断价值

指标	AUC	P值	95%CI	cut-off值	敏感度(%)	特异度(%)	准确度(%)
INPR	0.820	＜0.001	0.747~0.879	0.95	77.78	77.60	77.60
APRI	0.786	＜0.001	0.709~0.850	1.26	88.89	64.80	66.40
FIB-4	0.818	＜0.001	0.745~0.878	4.63	88.89	68.80	74.80

下载: 导出CSV

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