血管性血友病因子抗原与白蛋白比值和糖萼素指数评分对乙型肝炎肝硬化食管静脉曲张的预测价值

韩才均; 黄媛; 粘彬; 朴美花

doi:10.3969/j.issn.1001-5256.2022.12.013

血管性血友病因子抗原与白蛋白比值和糖萼素指数评分对乙型肝炎肝硬化食管静脉曲张的预测价值

DOI: 10.3969/j.issn.1001-5256.2022.12.013

韩才均^a,
黄媛^b,
粘彬^c,
朴美花^a, , ,

a.
延边大学附属医院检验科，吉林延吉 133000
b.
延边大学附属医院消化内科，吉林延吉 133000
c.
延边大学附属医院超声科，吉林延吉 133000

基金项目:

延边大学应用基础项目 (2020-45)

伦理学声明：本研究方案于2020年12月5日经由延边大学附属医院伦理委员会审批，批号：(2020)伦审字(211)。

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：韩才均负责课题设计，资料分析，撰写论文；黄媛、粘彬参与收集数据，拟定写作思路及修改论文；朴美花参与修改论文及最后定稿。

详细信息

通信作者:
朴美花，2224595359@qq.com

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出版历程
- 收稿日期: 2022-06-21
- 录用日期: 2022-07-25
- 出版日期: 2022-12-20

Value of von Willebrand factor antigen-to-albumin ratio and glycocalicin index in predicting esophageal varices in hepatitis B cirrhosis

a.
Department of Medical Laboratory, The Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, China
b.
Department of Gastroenterology, The Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, China
c.
Department of Ultrasonography, The Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, China

Research funding:

Applied Foundation Research Project of Yanbian University (2020-45)

More Information

Corresponding author: PIAO Meihua, 2224595359@qq.com (ORCID: 0000-0003-2621-6590)

摘要

摘要: 目的与血管性血友病因子抗原(vWF-Ag)与血小板比值(VITRO)评分比较，探讨vWF-Ag与白蛋白比值(VAR)和糖萼素指数(GCI)评分在预测食管静脉曲张(EV)发生及分级中的临床价值。方法回顾性分析2020年4月—2021年12月于延边大学附属医院住院的乙型肝炎肝硬化患者146例，以胃镜检查为标准，对EV进行诊断和分级。计算VITRO、VAR和GCI值，分析其与EV相关性。正态分布计量资料两组间比较采用t检验，多组间比较采用单因素方差分析；非正态性分布计量资料两组间比较采用Mann-Whitney U检验。计数资料组间比较采用χ²检验。采用Logistic回归模型分析EV的预测因素。使用受试者工作特征曲线(ROC曲线)评估各指标的诊断准确性。结果胃镜检查显示无EV患者54例，轻、中、重度EV患者分别为30、33和29例。EV患者的VAR和GCI评分显著高于无EV患者，差异有统计学意义(t值分别为-5.819、-3.449，P值均＜0.001)。线性回归显示VAR和GCI均随EV分级而升高(P值分别为0.002、0.005)。多变量回归分析确定VAR(风险比=1.46，95%CI：1.21~ 1.75，P＜0.001)和GCI(风险比=1.84，95%CI：1.22~2.77，P=0.003)与EV独立相关。VITRO评分诊断EV和重度EV的ROC曲线下面积(AUC)分别为0.718和0.863；临界值分别为2.77和5.37。VAR和GCI诊断EV的AUC分别为0.745和0.710，临界值分别为8.88和1.70；两者诊断重度EV的AUC分别为0.755和0.787，临界值分别为9.81和2.00。VAR联合GCI对EV诊断效能明显优于VITRO(P=0.009)，其AUC为0.808，敏感度为55.43%，特异度为94.44%；而联合模型对重度EV的AUC为0.869，与VITRO比较差异无统计学意义(P=0.421)。结论 VAR和GCI评分是预测乙型肝炎肝硬化患者EV和风险分层的潜在非侵入性标志物。
- 乙型肝炎 /
- 肝硬化 /
- 食管和胃静脉曲张
Abstract: Objective To investigate the clinical value of von Willebrand factor antigen-to-albumin ratio (VAR) score and glycocalicin index (GCI) score in predicting the development and classification of esophageal varices in comparison with von Willebrand factor antigen-to-platelet ratio (VITRO) score. Methods A retrospective analysis was performed for 146 patients with hepatitis B cirrhosis who were hospitalized from April 2020 to December 2021, and esophageal varices (EV) was diagnosed and graded with the results of gastroscopy as the standard. VITRO, VAR, and GCI were calculated, and their association with EV was analyzed. The t-test was used for comparison of normally distributed continuous data between two groups, and a one-way analysis of variance was used for comparison between multiple groups; 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 groups. A logistic regression model analysis was used to identify the predictive factors for EV, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of each index. Results Gastroscopy showed 54 patients without EV, 30 with mild EV, 33 with moderate EV, and 29 with severe EV. The patients with EV had significantly higher VAR and GCI scores than those without EV (t=-5.819 and -3.449, both P < 0.001). The linear regression analysis showed that VAR and GCI increased with the increase in EV grade (P=0.002 and 0.005). The multivariate logistic regression analysis showed that VAR (odds ratio [OR]=1.46, 95% confidence interval [CI]: 1.21-1.75, P < 0.001) and GCI (OR=1.84, 95%CI: 1.22-2.77, P=0.003) were independently associated with EV. VITRO score had an area under the ROC curve (AUC) of 0.718 in diagnosing EV and 0.863 in diagnosing severe EV, with the optimal cut-off values of 2.77 and 5.37, respectively. VAR and GCI had an AUC of 0.745 and 0.710, respectively, in diagnosing EV, with the optimal cut-off values of 8.88 and 1.70, respectively; VAR and GCI had an AUC of 0.755 and 0.787, respectively, in diagnosing severe EV, with the optimal cut-off values of 9.81 and 2.00, respectively. VAR combined with GCI had significantly better efficacy than VITRO in diagnosing EV (P=0.009), with an AUC of 0.808, a sensitivity of 55.43%, and a specificity of 94.44%; VAR combined with GCI had an AUC of 0.869 in diagnosing severe EV, which was similar to VITRO (P=0.421). Conclusion VAR and GCI scores are potential noninvasive markers for the prediction and risk stratification of EV in patients with hepatitis B cirrhosis.
- Hepatitis B /
- Liver Cirrhosis /
- Esophageal and Gastric Varices

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图 1 VAR与食管静脉曲张的相关性

Figure 1. The association of VAR score with esophageal varices

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图 2 GCI与食管静脉曲张的相关性

Figure 2. The association of GCI score with esophageal varices

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图 3 GCI、VAR和VITRO诊断EV(图a)及重度EV(图b)的ROC曲线比较

Figure 3. Comparison of the areas under the receiver operating curve for the GCI, VAR and VITRO score for diagnosing esophageal varices and severe esophageal varices

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表 1 EV组和无EV组患者基本特征

Table 1. Comparisons of characteristics between EV and non-EV in patients with cirrhosis

指标	无EV组(n=54)	EV组(n=92)	统计值	P值
年龄(岁)	56.97±12.97	57.55±12.26	t=-0.276	0.345
男/女(例)	37/17	59/33	χ²=0.291	0.590
HBV DNA(log₁₀ IU/mL)	3.6(3.0~5.1)	3.7(3.0~4.9)	Z=-0.409	0.682
脾脏厚度(mm)	35.90±6.46	38.67±8.84	t=-2.183	0.031
PLT(10⁹/L)	132.58±72.91	93.76±42.89	t=3.579	0.001
vWF-Ag(%)	277.43±65.45	316.80±87.30	t=-2.634	0.009
Alb(g/L)	35.52±5.61	31.83±5.20	t=4.026	＜0.001
TBil(μmol/L)	41.8(27.8~61.5)	48.3(37.9~70.6)	Z=-0.461	0.645
Cre(μmol/L)	72.3(60.5~100.6)	78.0(65.4~120.4)	Z=-1.098	0.272
PT-INR	1.26(1.07~1.42)	1.47(1.19~1.79)	Z=-3.083	0.002
GC(ng/mL)	0.92±0.50	0.89±0.27	t=0.441	0.661
MELD评分	11.17±4.75	15.66±6.09	t=-4.659	＜0.001
Child-Pugh评分	6.31±1.43	8.16±1.86	t=-6.740	＜0.001
Child-Pugh分级(A/B/C, 例数)	36/18/0	23/44/25	χ²=30.980	＜0.001
GCI	2.00±1.16	2.89±1.67	t=-3.449	＜0.001
VITRO	2.58±1.25	4.43±3.25	t=-4.871	＜0.001
VAR	7.89±1.98	10.36±3.13	t=-5.819	＜0.001

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表 2 EV危险因素的Logistic回归分析

Table 2. Univariable and multivariable analysis of risk factors for esophageal varices

指标	单因素分析		多因素分析(模型1)		多因素分析
指标	OR(95%CI)	P值	OR(95%CI)	P值	OR(95%CI)	P值
PLT(10⁹/L)	0.99(0.98~0.99)	0.001
vWF-Ag	1.01(1.00~1.01)	0.001
Alb(g/L)	0.88(0.82~0.94)	＜0.001
PT-INR	4.18(1.61~10.82)	0.003
MELD评分	1.21(1.10~1.32)	＜0.001	1.16 (1.05~1.27)	0.003	1.17 (1.07~1.29)	0.001
VAR	1.46(1.24~1.73)	＜0.001			1.46 (1.21~1.75)	＜0.001
GCI	1.85(1.27~2.59)	＜0.001			1.84 (1.22~2.77)	0.003
VITRO	1.73(1.31~2.28)	＜0.001	1.24 (1.68~2.28)	0.001

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表 3 研究参数对预测EV的诊断性能比较

Table 3. Comparison of the diagnostic performance of study variables for esophageal varices

组别	AUC(95%CI)	cut-off值	敏感度(%)	特异度(%)	P值
GCI	0.710(0.629~0.782)	1.70	84.78	53.70	＜0.001
VAR	0.745(0.666~0.813)	8.88	70.65	70.37	＜0.001
VITRO	0.718(0.638~0.789)	2.77	65.22	72.22	＜0.001
GCI+VAR	0.808(0.735~0.869)		55.43	94.44	＜0.001

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表 4 研究参数对重度EV的诊断性能比较

Table 4. Comparison of the diagnostic performance of study variables for severe esophageal varices

组别	AUC(95%CI)	cut-off值	敏感度(%)	特异度(%)	P值
GCI	0.787(0.712~0.850)	2.00	96.55	49.57	＜0.001
VAR	0.755(0.677~0.822)	9.81	75.86	66.67	＜0.001
VITRO	0.863(0.796~0.914)	5.37	65.52	92.31	＜0.001
GCI+VAR	0.869(0.803~0.919)		89.66	72.65	＜0.001

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参考文献(13)

[1]	Chinese Society of Spleen and Portal Hypertension Surgery, Chinese Society of Surgery, Chinese Medical Association. Expert consensus on diagnosis and treatment of esophagogastric variceal bleeding in cirrhotic portal hypertension (2015 edition)[J]. Chin J Pract Surg, 2015, 35(10): 1086-1090. DOI: 10.7504/CJPS.ISSN1005-2208.2015.10.16. 中华医学会外科学分会门静脉高压症学组. 肝硬化门静脉高压症食管、胃底静脉曲张破裂出血诊治专家共识(2015)[J]. 中国实用外科杂志, 2015, 35(10): 1086-1090. DOI: 10.7504/CJPS.ISSN1005-2208.2015.10.16.
[2]	POISSON J, LEMOINNE S, BOULANGER C, et al. Liver sinusoidal endothelial cells: Physiology and role in liver diseases[J]. J Hepatol, 2017, 66(1): 212-227. DOI: 10.1016/j.jhep.2016.07.009.
[3]	IWAKIRI Y, GROSZMANN RJ. Vascular endothelial dysfunction in cirrhosis[J]. J Hepatol, 2007, 46(5): 927-934. DOI: 10.1016/j.jhep.2007.02.006.
[4]	XU J, LIU Y, LOU WZY, et al. The anti-liver fibrosis effect of Kangxian Ruangan prescription: A cell study based on hepatic sinusoidal capillarization[J]. J Clin Hepatol, 2020, 36(2): 319-323. DOI: 10.3969/j.issn.1001-5256.2020.02.017. 许杰, 刘艳, 楼汪洲洋, 等. 基于肝窦毛细血管化探讨抗纤软肝方抗肝纤维化的作用机制[J]. 临床肝胆病杂志, 2020, 36(2): 319-323. DOI: 10.3969/j.issn.1001-5256.2020.02.017.
[5]	MAIERON A, SALZL P, PECK-RADOSAVLJEVIC M, et al. Von willebrand factor as a new marker for non-invasive assessment of liver fibrosis and cirrhosis in patients with chronic hepatitis C[J]. Aliment Pharmacol Ther, 2014, 39(3): 331-338. DOI: 10.1111/apt.12564.
[6]	GARCIA-MARTINEZ R, ANDREOLA F, MEHTA G, et al. Immunomodulatory and antioxidant function of albumin stabilises the endothelium and improves survival in a rodent model of chronic liver failure[J]. J Hepatol, 2015, 62(4): 799-806. DOI: 10.1016/j.jhep.2014.10.031.
[7]	FENG S, FENG HF, XU J, et al. Value of FibroScan and platelet count to spleen thickness ratio in predicting the degree of esophageal and gastric varices in liver cirrhosis[J]. J Clin Hepatol, 2021, 37(12): 2819-2823. DOI: 10.3969/j.issn.1001-5256.2021.12.018. 封爽, 冯慧芬, 徐晶, 等. 肝硬度值和血小板计数/脾脏厚径比率对肝硬化食管胃底静脉曲张程度的预测价值[J]. 临床肝胆病杂志, 2021, 37(12): 2819-2823. DOI: 10.3969/j.issn.1001-5256.2021.12.018.
[8]	BEER JH, BVCHI L, STEINER B. Glycocalicin: a new assay——the normal plasma levels and its potential usefulness in selected diseases[J]. Blood, 1994, 83(3): 691-702. DOI: 10.1182/blood.V83.3.691.691
[9]	WANG X, JIANG W, LI F, et al. Abnormal platelet kinetics are detected before the occurrence of thrombocytopaenia in HBV-related liver disease[J]. Liver Int, 2014, 34(4): 535-543. DOI: 10.1111/liv.12309.
[10]	HAMETNER S, FERLITSCH A, FERLITSCH M, et al. The VITRO score (Von Willebrand Factor Antigen/Thrombocyte Ratio) as a new marker for clinically significant portal hypertension in comparison to other non-invasive parameters of fibrosis including ELF test[J]. PLoS One, 2016, 11(2): e0149230. DOI: 10.1371/journal.pone.0149230.
[11]	SIEDLECKI CA, LESTINI BJ, KOTTKE-MARCHANT KK, et al. Shear-dependent changes in the three-dimensional structure of human von Willebrand factor[J]. Blood, 1996, 88(8): 2939-2950. DOI: 10.1182/blood.V88.8.2939.bloodjournal8882939
[12]	UEMURA M, FUJIMURA Y, KO S, et al. Pivotal role of ADAMTS13 function in liver diseases[J]. Int J Hematol, 2010, 91(1): 20-29. DOI: 10.1007/s12185-009-0481-4.
[13]	CARACENI P, TUFONI M, ZACCHERINI G, et al. On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites[J]. J Hepatol, 2021, 74(2): 340-349. DOI: 10.1016/j.jhep.2020.08.021.