Evaluation Value Of Hepatic Hemodynamics Ultrasonic Parameters,vWF-Ag And SCD163 For High-risk Esophageal Varices,Prognosis And Antiviral Therapy Response In Patients With Cirrhosis

Background Portal hypertension is the most important pathophysiological basis of serious complications and death in cirrhotic patients.So all cirrhotic patients should evaluate the severity of portal hypertension and related complications,especially high-risk esophageal varices and esophageal variceal hemorrhage,and should explore risk factors of predicting the prognosis.Although HVPG and gastroscopy are acknowledged as the clinical gold standard for evaluation of the portal hypertension and esophageal varices,but both techniques are invasive,highly technical requirements,poorly accepted by the patients if repeatedly required.It is a clinical research focus for exploring the ideal noninvasive examination index and methods which can effectively assess portal hypertension,high-risk esophageal varices including the first hemorrhage,and the influence of drug treatment for portal hypertension.Objective1.To explore the diagnostic values of the ultrasound parameters of portal venous congestion index(PV-CI),hepatic vein damping index(HV-DI)and contrast-enhanced ultrasound parameters such as hepatic vein arrival time(HVAT)and hepatic vein-hepatic artery interval time(HV-HA),et al and peripheral blood v WF-Ag and s CD163 level for evaluation of high-risk esophageal varices and hemorrhage as well as the prognosis of cirrhotic patients.2.To prospectively evaluate the effects of antiviral therapy on liver hemodynamics ultrasonic parameters and peripheral blood v WF-Ag and s CD163 in patients with hepatitis B cirrhosis.Methods1.From July 2012 to November 2014,196 cirrhotic inpatients were consecutively enrolled and ultrasonographic parameters were measured including PVD,PVV,PV-CI,SVD,SL,HV-DI HAAT,HVAT,HV-HA,PVAT and PV-HA before upper endoscopic examination.Peripheral blood v WF-Ag and s CD163 of all recruiting patients and 15 healthy volunteers were collected by Enzyme linked immunosorbent method(ELISA).Finally,190 patients completed the following studies: 1)All patients completed the endoscopy examinations for assess the degree of the esophageal varices within one week after ultrasound examinations.The degree of esophageal varices and all ultrasound parameters as well as peripheral blood markers were analyzed.Some parameters which could effectively screening and diagnose high-risk esophageal varices were selected by AUROC method(derivation set).Another 80 inpatients with liver cirrhosis were further enrolled(validation set)(From February 2015 to August 2017),and serological markers and ultrasound parameters above slected were further validated for the diagnostic accuracy of high-risk esophageal varices in validation set.2)143 cases high-risk EVs(all for medium/severe EVs)were checked out by endoscopy examinations.Of the 143 high risk EVs patients,68 patients without history of EVH were prospectivly followed up to survey the first bleeding(The finish time of follow-up:December 31,2017).The first esophageal varices hemorrhage and all baseline ultrasound parameters as well as peripheral blood markers were analyzed.3)190 cases cirrhotic inpatients were prospectivly followed up to survey the death events.(The finish time of follow-up:December 31,2017).The survival conditions of all cirrhotic inpatients and all baseline ultrasound parameters as well as peripheral blood markers were analyzed.2.From July 2012 to February 2014,Seventy consecutive eligible HBV-related cirrhotic inpatients were enrolled in the prospective study.Fifty-two received different nucleoside analogs monotherapy and 18 denied antiviral therapy.Their liver biochemistry profiles and HBV-DNA were measured at the baseline and every 3 months.Peripheral blood v WF and s CD163,as well as liver ultrasound Doppler parameters including portal vein diameter(PVD),portal vein velocity(PVV),portal vein congestion index(PV-CI),hepatic vein damping index(HV-DI),hepatic arterial arrival time(HAAT),hepatic vein arrival time(HVAT),intrahepatic cycle time(HV-HA),portal vein arrival time(PVAT)and portal vein-hepatic artery interval time(PV-HA)were measured at the baseline and the follow-up periods.Results1.In 190 cirrhotic inpatients,143 patients were found to have HEVs.PVD,PVV,PV-CI,SVD,SL,HV-DI,HVAT,HV-HA,PVAT,PV-HA,v WF-Ag and s CD163 were significantly associated with the presence of HEVs by univariate analysis.In patients with HEVs,the HV-DI yielded the highest AUROC(0.944).A optimum cutoff value of HV-DI 0.65 had a sensitivity of 82.5%,a specificity of 95.7%,a PPV of 98.3%,a NPV of 64.3% and a DA of 85.8%.The DA of HV-DI,v WF-Ag and s CD163 predicting HEVs were all greater than 80% and the AUROC of the three parameters were greater than 0.85.In the validation group,a optimum cutoff value of HV-DI 0.65 had still the highest accuracy for predicing of the HEVs with the AUROC 0.920 and had a sensitivity of 84.0% a specificity of 80.0%,a PPV of 87.5%,a NPV of 75.0% and a DA of 82.5%.The AUROC of v WF-Ag and s CD163 were 0.889 and 0.907.The DA of HV-DI and s CD163 predicting HEVs were both greater than 80% and the AUROC of the both parameters were greater than 0.90.The AUROC of baseline HV-DI,v WF-Ag and s CD163 predicting first HEVs bleeding was 0.965,0.999 and 0.965,respectively.When optimum cutoff value of HV-DI,v WF-Ag and s CD163 was 0.655,182.01 U/dl and 74.37 ng/ml,respectively,the DA,sensitivity and NPV of predicting first HEVs bleeding were all greater than 90.0%.HV-DI was positivly correlated with either v WF-Ag or s CD163 significantly(r>0.7,P< 0.01).COX regression analysis showed that HV-DI,peripheral blood v WF-Ag and sodium levels were independent risk factors affecting the prognosis of cirrhotic inpatients(P<0.05).2.In the antiviral group,all patients achieved complete virologic and liver biochemical responses after 3-month antiviral treatment.Furthermore,the response states were maintained till the follow-up endpoint.However,in the non-antiviral group,HBV DNA replication resulted in higher levels of ALT and AST compared to the baseline values(P<0.05).In the antiviral group,PVD,PV-CI,HV-DI,v WF-Ag and s CD163 were all significantly reduced than the baseline values(P <0.05),and PVV was significantly increased than the baseline value(P <0.05).Conclusions1.HV-DI,peripheral blood v WF-Ag and s CD163 can effectively predict the occurrence of moderate/severe EV and first bleeding,HV-DI was positivly correlated with either peripheral blood v WF-Ag or s CD163 significantly.HV-DI,peripheral blood v WF-Ag and sodium levels were the independent risk factors of affecting the prognosis of cirrhotic patients.2.Antiviral therapy could effectively suppress hepatocyte inflammation and alleviate the dysfunction of intrahepatic vascular endothelial and hepatic macrophages,which might improve hepatic hemodynamic function in HBV-related cirrhosis.