Von Willebrand Factor As A Novel Noninvasive Predictor Of Portal Hypertension And Esophageal Varices In Hepatitis B Patients With Cirrhosis

Objective and Aims:Cirrhosis is the final pathology results of various chronic liver diseases. Liver cirrhosis caused the abnormal of vascular structure and resulted in the increased liver vascular tension, leading to the increased portal resistance and eventually causing the portal hypertension. Esophageal varices hemorrhage caused by portal hypertension is an important cause of death in patients with liver cirrhosis. If not treated timely, it will be a serious threat to the survival of patients. Early prediction of portal hypertension and esophageal varices in patients with liver cirrhosis, can carry out early treatment, and effectively reduce the mortality. HVPG is considered to be the gold standard for the diagnosis of portal hypertension. HVPG is an invasive detection with high technical requirements; it is not regarded as a routine detection method. Early predicting esophageal varices can provide evidence for managing cirrhotic patients. Upper gastrointestinal endoscopy is considered to be the gold standard for the detection of esophageal and gastric varices. Upper gastrointestinal endoscopy is required in all patients with liver cirrhosis. However, because of the risk of rupture of varicose veins and the influence of the technology, there are still some limitations. And the new guidelines put forward, it is critical to find a non-invasive method for the prediction of portal hypertension and esophageal varices. At present, there is no perfect noninvasive method to assess PH and esophageal varices.Von Willebrand factor (vWF) can be used as an important marker of vascular endothelial cell activation and injury. In patients with cirrhosis, plasma levels of vWF were increased with the severity of the patient’s Child-Pugh grade. Recent studies have found that there is a positive correlation between plasma vWF levels and HVPG in patients with liver cirrhosis. But no study showed the predict value of plasma vWF levels in the diagnosis of portal hypertension and esophageal varices in hepatitis B patients with cirrhosis. Therefore, we aimed to further investigate a new noninvasive factor to predict the portal hypertension and esophageal varices in hepatitis B patients with cirrhosis.Material and Methods:A total of 60 hepatitis B patients with cirrhosis and 45 healthy subjects were enrolled in this study. The blood samples of normal control group and patients were collected. Levels of vWF were measured using enzyme-linked immunosorbent assays kits. The other markers (platelet, albumin, bilirubin, INR, APRI) were also examined. All patients underwent hepatic venous pressure gradient (HVPG) and esophagogastroduodenoscopy. Receiver operator characteristic (ROC) curve was constructed and each area under the curve (AUC) was calculated to determinate test performance for prediction the dgree of portal hypertension and esophageal varices.Results:Plasma vWF was increased significantly in hepatitis B patients with cirrhosis, showing the highest diagnostic efficacy in the diagnosis of portal hypertension and esophageal varices. Cutoff values of plasma vWF (1510.5 mU/mL and 1701 mU/mL) showed high positive predictive value (PPV,90.2% and 87.5%) in predicting clinically significant portal hypertension and severe portal hypertension. Cutoff values of vWF (1414 mU/ml and 1990 mU/mL, PPV 90.3% and 86.3%, respectively) were provided to detect the presence and degree of esophageal varices.Conclusion:The vWF is a noninvasive predictor of portal hypertension and esophageal varices in hepatitis B patients with cirrhosis. Increased levels of vWF in liver tissues may induce the elevated plasma vWF levels, but molecular mechanism is needed for further study.