The Clinical Analysis And Serum Proteomics Research Of Portal Vein Thrombosis In Liver Cirrhosis

Objective:Investigate the related risk factors and clinical characteristics of portal vein thrombosis in Liver cirrhosis and identify differential expressed proteins in patients with Portal vein thrombosis and without Portal vein thrombosis in liver cirrhosis.Methods:A retrospective analysis was performed on the clinical data in 218 cases who were diagnosed as liver cirrhosis and treated form June 2013 to June 2017 in Infectious Disease Center of the First Affiliated Hospital of Xinjiang Medical University.Among them,109cases were patients with PVT,109 cases were patients without PVT.General information,clinical manifestations,complications,results of laboratory examination and imaging data were analyzed.Continuous data were applied by t-test,categorical data were applied by chi-square test,and the unconditional logistic regression model was analyzed the independent risk factors of PVT in liver cirrhosis.An isobaric tags for relative and absolute quantification(iTRAQ)based proteomic analysis was used to identify the differential expressed proteins in 45 patients with liver cirrhosis(22 cases were patients with portal vein thrombosis,23 cases were patients without portal vein thrombosis),and the two significantly differential proteins(FCGR2A,SNAP23)related to platelet activation were further validated using Enzyme-linked immunosorbent method(ELISA)in two grops.Results:Compared to NON-PVT group,age,gender,nation,smoking,etiology,white blood cell,platelet count,prothrombin time,international normalized ratio,activated partial prothrombin,fibrinogen,creatinine,cystatinC,totalbilirubin,directbilirubin,alanine aminotransferase,gamma glutamyl transpeptidase,alkaline phosphatase,the length of spleen,the width of the splenic vein,weren't significantly different in PVT group.but the Child-Pugh score(x~2=20.293,P=0.0001),splenectomy(x~2=11.869,P=0.001),the width of portal vein(t=3.125,P=0.002),width of spleen(t=2.283,P=0.024),hemoglobin(t=-3.751,P=0.000),albumin(t=-3.924,P=0.000),D-dimer(t=5.861,P=0.000),the effects of fibrin degradation products(t=3.110,P=0.002)were significantly different in PVT group.Diarrhea,hepatic encephalopathy,hepatorenal syndrome weren't statistically significant different in two groups(P>0.05),but abdominal pain(x~2=4.598,P=0.032),fever(x~2=7.72,P=0.005),upper gastrointestinal bleeding(x~2=18.435,P=0.0001),spontaneous peritonitis(x~2=16.987,P=0.000)were statistically significant different(P<0.05)in two groups.D-dimer,fibrin degradation products,Child-Pugh score,splenectomy are independent risk factors of PVT in liver cirrhosis.(OR=0.686,0.161,3.193,9.515),(P=0.000,0.007,0.021,0.007).Totally,86 different proteins in two groups were identified using iTRAQ.Among 86 proteins,32 up-regulated proteins(ratio?1.2,P<0.05)and 54 down-regulated proteins(ratio?-0.83,P<0.05)were identified in PVT group.These different expression proteins were involved in cellular component,biological process,molecular function.There were five pathways that were significantly affected in PVT.17 of 86 different expression proteins had connection with the five pathways.Two most significant different expression proteins(FCGR2A,SNAP23)related to platelet activation function were further validated by ELISA in two groups.The level of FCGR2A was significantly elevated in serum of patients with Portal vein thrombosis compared with patients without Portal vein thrombosis(P<0.008).The area under the curve of this protein to distinguish patients with Portal vein thrombosis from patients without Portal vein thrombosis was 0.729,with sensitivity of 86.36%and specificity of 42.89%.The level of SNAP23 was significantly decreased in patients with Portal vein thrombosis compared with patients without Portal vein thrombosis(P<0.001).The area under the curve of this protein to distinguish patients with Portal vein thrombosis from patients without Portal vein thrombosis was 0.8024,with sensitivity of 100%and specificity of60.87%.Conclusion:D-dimer,the width of portal vein,Child-Pugh score,splenectomyare independent risk factors of PVT in liver cirrhosis.PVT can aggravate clinical symptoms and increase complications of the patients.FCGR2A,SNAP23 that were statistically difference in PVT group compared with Non-PVT group may be a biological markers in serum of portal vein thrombosis in liver cirrhosis.