Analysis Of Risk Factors For Rebleeding From Secondary Prophylaxis Of Variceal Bleeding In Cirrhotic People:TIPS Vs.Endoscopic Therapy

Objectives:Variceal hemorrhage is a major complication of portal hypertension that still causes high mortality in patients with cirrhosis,with a 5-15%annual incidence.The medical Guide has recommended endoscopy therapy with non-selective beta blockers(NSBBs)as the standard treatment of acute variceal hemorrage.But early placement of transjungular intrahepatic portosystemic shunt(TIPS)has been shown to be associated with improved survival,lower rebleeding rate,without the increase of hepatic encephalopathy.But,it quite common that plenty of patient come to hospital for treatment of varices without acute bleeding.Thus,for secondary prophylaxis of variceal bleeding,alternative criteria have been proposed to refine the criteria used to identify candidates for TIPS.nevertheless,the true survival benefit provided(or not)by TIPS compared with standard treatment in the different risk categories has not been investigated in specifically designed comparative studies.Design:We collected data on 519 consecutive patients with cirrhosis who all have a history of variceal bleeding over 5 days for further treatment in the Department of Gastroenterology of Shandong Provincial Hospital between October 2009 and October 2019.Of these,103 patients received TIPS,and 419 patients received standard treatment.the Fine and gray competing risk regression model was used to compare the outcomes between the two groups that were stratified based on the currently available risk stratification systems after adjusting for liver disease severity and other potential confounders.Statistical analysis was performed using Microsoft R Open 3.5.1.Continuous variables are described as the mean±standard deviation or the median,and the groups were compared using t-tests or the Wilcoxon rank sum test.The categorical variables were described by frequency(percent)and were tested using the Wilcoxon rank sum test,and the nonhierarchical variables were assessed by chi-square or Fisher's exact tests.The rebleeding rate,survival rate,and HE incidence rate of the two groups were compared by the Kaplan-Meier method and the log-rank test.Cox proportional hazard analyses were used for univariate and multivariate analyses of the end points.A two-sided p-value<0.05 was considered statistically significant.Results:1.There are total 251 patients finally occurring bleeding,(32 in TIPS group and 219 in endoscopy group).The bleeding ratio of TIPS group and Endoscopy group is separately 31.1%and 52.3%.TIPS group has lower potential to occur variceal rebleeding(HR=0.56;95%CI:0.38-0.82;p=0.002)and also be the independent protective factor of variceal rebleeding(HR=0.57;95%CI:0.38-0.84;p<0.005).And alcoholic cirrhosis tend to have high risk of variceal rebleeding than Hepatitis B cirrhosis(HR=0.56;95%CI:0.38-0.82;p=0.002).Then,blood sodium level is the protective factor of rebleeding(HR=0.95;95%CI:0.91-0.99;p=0.023).And Alanine Aminotransferase(ALT)is the independent risk factor of variceal rebleeding(HR=1.01;95%CI:1-1.01;p=0.003).2.There are total 101 patients finally occurring death,(18 in TIPS group and 83 in endoscopy group).The bleeding ratio of TIPS group and Endoscopy group is separately 17.5%and 19.8%.There is no difference between TIPS group and standard endoscopy therapy in mortality rate.Hepatitis C cirrhosis(HR=2.48;95%CI:1.01-5;p=0.048)and cirrhosis with mix etiology(HR=3.6;95%CI:1.29-10.5;p=0.015)seems to have high risk of mortality than Hepatitis B cirrhosis.Nevertheless,Child-Pugh score(HR=1.32;95%CI:1.2-1.46;p<0.001),MELD score(HR=1.12;95%CI:1.07-1.16;p<0.001),MELD-Na score(HR=1.11;95%CI:1.07-1.15;p<0.001),age(HR=1.05;95%CI:1.03-1.17;p<0.001),AST(HR=1.01;95%CI:1-1.01;p=0.009),ALT(HR=1.01;95%CI:1-1.01;p=0.020),TBLB(HR=1.01;95%CI:1-1.02;p=0.005),PTs(HR=1.07;95%CI:1.04-1.1;p<0.001)and INR(HR=2.27;95%CI:1.72-3;p<0.001)are all the risk factor of mortality rate.And Hb and blood sodium level are the protective factor of mortality.And age(HR=1.05;95%CI:1.03-1.07;p<0.001)and ALT(HR=1.01;95%CI:1-1.01;p=0.003)are also the independent risk factor of mortality.3.There are total 50 patients finally occurring hepatic encephalopathy(26 in TIPS group and 24 in endoscopy group).The bleeding ratio of TIPS group and Endoscopy group is separately 25.24%and 5.7%.TIPS therapy is a risk factor of hepatic encephalopathy(HR=6.23;95%CI:3.94-10.95;p<0.001).Partial portal vein thrombosis is more likely to have encephalopathy(HR=2.4;95%CI:1.36-4.24;p=0.003).And patience who has encephalopathy before therapy is more likely to get encephalopathy after(HR=8.34;95%CI:2.59-26.93;p<0.001).Moreover,Child-Pugh score(HR=1.27;95%CI:1.11-1.45;p=0.001),MELD score(HR=1.11;95%CI:1.06-1.16;p<0.001),MELD-Na score(HR=1.12;95%CI:1.08-1.17;p<0.001),PTs(HR=1.08;95%CI:1.05-1.11;p<0.001)and INR(HR=2.47;95%CI:1.79-3.41;p<0.001)are all the risk factor of encephalopathy.And blood albumin is the protective factor of encephalopathy(HR=0.92;95%CI:0.88-0.96;p<0.001).Furthermore,age is the independent risk of encephalopathy.4.The Log-Rank test analyze TIPS group has lower bleeding rate(p=0.0024).And in Child-Pugh A grade patients,TIPS can improve the rebleeding rate(p=0.0076).But for Child-Pugh B/C grade patients,there is no difference between two therapy group.Also in MELD score(?11point)TIPS can improve the rebleeding rate(p=0.0025).there is no difference between two therapy group in MELD score(?12 point).Then,TIPS therapy improve rebleeding rate both GOV1 type and GOV2/IGV type varicose.5.There is no difference of mortality between TIPS group and endoscopy therapy group(p=0.68),regardless of Child-Pugh grade,MELD grade and the variceal type under endoscopy.6.TIPS therapy can cause a higher rate of hepatic encephalopathy(p<0.001).And in Child-Pugh A/B grade,MELD score(?18 point)patients,TIPS can increase the rate of hepatic encephalopathy(p<0.001),not in Child-Pugh C grade and MELD(?19 point)patients.And TIPS therapy improve encephalopathy rate both GOV1 type and GOV2/IGV type varicose.Conclusions:1.TIPS therapy can improve Child-Pugh A grade and MELD score(?11 point)rebleeding rate,and increase hepatic encephalopathy rate in Child-Pugh A/B grade and MELD score(?18point)patients,with no no difference in total mortality.2.Patients in different MELD score who choose TIPS as treatment are all have higher 1-year encephalopathy rate.GOV2/IGV type varicose patients in different MELD score who choose TIPS as treatment are all have higher 1-year encephalopathy rate.Not same with GOV1type patients.3.Alcoholic cirrhosis,Hepatic B virus cirrhosis and hyponatremia are all the risk factor of variceal rebleeding.ALT and endoscopy therapy are both the independent risk factor in total rebleeding rate.