血管性假血友病因子抗原水平及VITRO评分在不同类型肝病患者中的特征及临床意义

摘要/Abstract

摘要： 目的探讨血管性假血友病因子(von Willebrand factor, vWF)抗原水平和VITRO评分(vWF/血小板计数)对不同类型肝病患者的临床价值。方法收集2017年1月至2017年9月上海交通大学医学院附属瑞金医院感染科连续住院的肝损伤患者共122例,其中急性肝病患者50例,慢性肝病患者72例。急性肝病患者再分为急性肝损伤亚组43例,急性/亚急性肝衰竭亚组7例,慢性肝病组分为慢性肝炎亚组21例,慢加急性肝衰竭亚组12例,肝硬化亚组39例。检测并分析所有患者血浆vWF:Ag水平与VITRO(vWF/血小板计数)评分在各组、亚组之间的表达特征及临床意义。结果慢性肝病组的血浆vWF:Ag检测值和VITRO评分分别为205.30 (185.30~235.35) 和2.47 (1.57~3.90),高于急性肝病组的172.30 (158.30~194.10)和1.00 (0.82~1.21),差异有统计学意义(P<0.01)。亚组分析中,慢加急性肝衰竭亚组的血浆vWF:Ag检测值和VITRO评分分别为225.40(211.20~237.45)和3.61(2.92~4.69),高于急性/亚急性肝衰竭亚组的196.30 (190.30~210.30)和1.28(0.89~1.71),差异均有统计学意义(P<0.05)。ROC曲线分析显示,在所有患者中,血浆vWF:Ag检测值和VITRO诊断慢性肝病的AUC分别为0.812(95% CI:0.734~0.890,P<0.01)与0.891(95% CI:0.828~0.953,P<0.01);当界值分别为185%和1.35时,其诊断的敏感度为81.9%和79.7%,特异度为70.0%和72.9%,阳性预测值为79.7%和89.2%,阴性预测值为72.9%和82.0%,诊断准确率为77.0%和86.1%。相对于急性/亚急性肝衰竭,血浆vWF:Ag检测值和VITRO评分诊断慢加急性肝衰竭的AUC分别为0.833(95% CI:0.610~1.000,P<0.05)和0.940(95% CI:0.000~1.000,P<0.01);当界值分别为215%和2.00时,其诊断的敏感度分别为100.0%和100%,特异度为75.0%和91.7%,阳性预测值为70.0%和87.5%,阴性预测值为100.0%和100%,诊断准确率为84.2%和94.7%。结论慢性肝病患者的血浆vWF:Ag水平与VITRO评分高于急性肝病患者,肝衰竭时尤其明显,具有一定的临床诊断价值。VITRO的诊断价值大于vWF:Ag。

关键词: 血管性假血友病因子, 肝硬化, 肝衰竭, 急慢性肝损伤

Abstract: Objective To evaluate the diagnostic accuracy of von Willebrand factor antigen (vWF: Ag) and von Willebrand factor antigen/thrombocyte ratio (VITRO) score in different types of liver diseases in Chinese patients. Methods A total of 122 patients admitted from January 2017 to September 2017 were enrolled. Plasma vWF: Ag was tested in all patients, and VITRO score was calculated upon admission. All cases were divided into acute group (50 cases) and chronic group (72 cases), which were further classified into 5 subgroups, including acute liver injury subgroup (43 cases), acute/subacute liver failure subgroup (7 cases), chronic liver injury subgroup (21 cases), acute on chronic liver failure subgroup (12 cases) and liver cirrhosis subgroup (39 cases). Clinical significance and characteristics of plasm vWF:Ag level and VITRO score were determined using Mann-Whitney U test and receiver operating characteristic (Hayashi, #19) curve analysis. Results Demographic characteristic were similar in acute and chronic liver disease groups except age. Plasma vWF:Ag levels [205.30 (185.30~235.35) vs 172.30 (158.30~194.10), P<0.01] and VITRO scores [2.47 (1.57~3.90) vs 1.00 (0.82~1.21), P<0.01] were both significantly higher in chronic group than acute group. Plasma vWF-Ag levels [225.40 (211.20~237.45) vs 196.30 (190.30~210.30), P<0.05] and VITRO score [3.61 (2.92~4.69) vs 1.28 (0.89~1.71), P<0.01] were both higher in acute on chronic/chronic liver failure subgroup than acute/subacute liver failure subgroup. ROC curve analysis revealed that the area under curve (AUCs) for the diagnosis of chronic liver disease was 0.812 (95% CI: 0.734~0.890, P<0.01) for vWF: Ag and 0.891 (95% CI: 0.828~0.953, P<0.01) for VITRO score. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy for chronic liver disease were 81.9%, 70.0%, 79.7%, 72.9%, 77.0% using a vWF: Ag cut-off value of 185%, and were 79.7%, 72.9%, 89.2%, 82.0%, 86.1% using a VITRO cut-off value of 1.35, respectively. The AUCs for the diagnosis of acute on chronic liver failure was 0.833 (95% CI: 0.610~1.000, P<0.05) for vWF: Ag and 0.940 (95% CI: 0.000~1.000, P<0.01) for VITRO score. The sensitivity, specificity, positive predictive, negative predictive value and diagnostic accuracy for acute on chronic liver failure were 100.0%, 75.0%, 70.0%, 100.0% and 84.2% using a vWF: Ag cut-off value of 215%, and were 100%, 91.7%, 87.5%, 100% and 94.7% using a VITRO cut-off value of 2.00, respectively.Conclusion Elevated vWF: Ag level and VITRO score are characteristic of chronic liver diseases in Chinese patients, especially in patients with liver failure. VITRO score is of greater diagnostic value than vWF: Ag level.

Key words: von Willebrand factor, Liver cirrhosis, Liver failure, Acute and chronic liver injury

庄焱, 王晓琳, 刘珂慧, 徐玉敏, 谢敬东, 林之莓, 王晖, 谢青, 郭清. 血管性假血友病因子抗原水平及VITRO评分在不同类型肝病患者中的特征及临床意义[J]. 肝脏, 2018, 23(1): 14-17.

ZHUANG Yan, WANG Xiao-lin, LIU Ke-hui, XU Yu-min, XIE Jin-dong, LIN Zhi-mei, WANG Hui, XIE Qing, GUO Qing. Clinical characteristics and significance of plasma von Willebrand factor antigen level and VITRO score in Chinese patients with various hepatic diseases[J]. Chinese Hepatolgy, 2018, 23(1): 14-17.

参考文献

[1] 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. Aliment Pharmacol Ther, 2014, 39: 331-338.
[2] Lisman T,Bongers TN,Adelmeijer J,et al. Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity. Hepatology, 2006,44: 53-61.
[3] Iwakiri Y,Groszmann RJ. Vascular endothelial dysfunction in cirrhosis. J Hepatol, 2007, 46: 927-934.
[4] Ferlitsch M,Reiberger T,Hoke M,et al. von Willebrand factor as new noninvasive predictor of portal hypertension, decompensation and mortality in patients with liver cirrhosis. Hepatology, 2012, 56: 1439-1447.
[5] La Mura V,Reverter JC,Flores-Arroyo A,et al. Von Willebrand factor levels predict clinical outcome in patients with cirrhosis and portal hypertension. Gut, 2011, 60: 1133-1138.
[6] Pramhas S,Homoncik M,Ferenci P,et al. von Willebrand factor antigen: a novel on-treatment predictor of response to antiviral therapy in chronic hepatitis C genotypes 1 and 4. Antivir Ther, 2010, 15: 831-839.
[7] 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. PLoS One, 2016, 11: e0149230.
[8] Hugenholtz GC,Adelmeijer J,Meijers JC,et al. An unbalance between von Willebrand factor and ADAMTS13 in acute liver failure: implications for hemostasis and clinical outcome. Hepatology, 2013, 58: 752-761.
[9] Agarwal B,Wright G,Gatt A,et al. Evaluation of coagulation abnormalities in acute liver failure. J Hepatol, 2012, 57: 780-786.
[10] Lisman T,Stravitz RT. Rebalanced hemostasis in patients with acute liver failure. Semin Thromb Hemost, 2015, 41: 468-473.
[11] 中华医学会感染病学分会肝衰竭与心脏学组,中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2012年版). 中华临床感染病杂志,2012,5:321-327.
[12] van Mourik JA,Romani de Wit T. Von Willebrand factor propeptide in vascular disorders. Thromb Haemost, 2001, 86: 164-171.
[13] Lisman T,Porte RJ. Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood, 2010, 116: 878-885.
[14] Tripodi A,Mannucci PM. The coagulopathy of chronic liver disease. N Engl J Med, 2011, 365: 147-156.
[15] Lisman T,Bakhtiari K,Adelmeijer J,et al. Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure. J Thromb Haemost, 2012, 10: 1312-1319.
[16] Villa E,Camma C,Marietta M,et al. Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis. Gastroenterology, 2012, 143:1253-1260、 e1-4.