Clinical characteristics and significance of plasma von Willebrand factor antigen level and VITRO score in Chinese patients with various hepatic diseases

Abstract

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

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.

References

[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.