Association Study And Influencing Factors On Increase Of Total Bilirubin At Early Stage After TIPS With UGT1A1 Gene Polymorphism

Part One: Influencing Factors on Increase of Total Bilirubin at Early Stage after TIPSObjective: To investigate the influencing factors of increase of total bilirubin at early stage after transjugular intrahepatic portosystemic shunt.Methods: 104 patients with elective TIPS treatment for hemorrhage due to portal hypertension and esophagogastric varices were selected from December 2017 to December 2019 of the Hepatobiliary Disease Center of 900 TH Hospital of Joint Logistics Support Force.According to whether there was a increase in total bilirubin at early postoperative period,it was divided into a control group and a case group.Logistic regression analysis was used to analyze the factors that increased total bilirubin at early stage after TIPS.Results: All 104 patients successfully established intrahepatic portal stent shunt.Portal pressure decreased from 43.00(36.00～48.00)mm Hg before operation to 28.00(25.00～31.00)mm Hg,the difference was statistically significant(Z =-8.857,P <0.001).The total bilirubin before TIPS was 18.40(14.20～24.10)μmol / L,and it increased to33.70(24.80～50.50)μmol / L 2 weeks after operation.The difference was statistically significant(Z =-8.775,P <0.001).Two weeks after operation,alanine aminotransferase,aspartate aminotransferase,and alkaline phosphatase were higher than that of preoperation,the difference was statistically significant.Univariate analysis showed that there were significant differences in preoperative total bilirubin,preoperative unconjugated bilirubin,preoperative alanine aminotransferase,preoperative Child-Pugh classification,preoperative MELD score,and postoperative portal vein branch imaging.Binary logistic regression analysis showed that preoperative total bilirubin,preoperative alanine aminotransferase,and postoperative portal vein branch imaging were significantly associated with postoperative total bilirubin elevation at early stage.Conclusion: 1.After TIPS,most patients have lower portal pressure than before,but liver function is damaged to some extent.2.The preoperative total bilirubin level and preoperative high alanine aminotransferase level are the risk factors for the increase of total bilirubin at early stage after TIPS,and the greater the number of portal vein branches after surgery is the protective factor.Part Two: Association Study on Increase of Total Bilirubin at Early Stage after TIPS with UGT1A1 gene PolymorphismObjective : To investigate the relationship between the common polymorphism of UGT1A1 gene and increase of total bilirubin at early stage after TIPS.Methods: 104 patients with elective TIPS treatment for hemorrhage due to portal hypertension and esophagogastric varices were selected from December 2017 to December 2019 of the Hepatobiliary Disease Center of 900 TH Hospital of Joint Logistics Support Force.According to whether there was a increase in total bilirubin in the early postoperative period,it was divided into a control group and a case group.Using the first-generation sequencing method to detect the four polymorphic sites in the promoter region TATA box,enhancer c.-3279 T> G,c.211G> A,c.686C> A of UGT1A1 gene,using genetic statistics analyze the correlation between the four loci alleles and their genotypes with increase of total bilirubin at the early stage after TIPS.Results: 1.TATA boxenhancer,c.-3279 T> G,c.211G> A and c.686C> A locus genotypes in the control group were in accordance with Hardy-Weinberg equilibrium test.2.2 alleles A、G and 3 genotypes AA、AG、GG were detected in c.211G> A locus,There is a increase in hormones,and the population carrying allele A has an increased risk of a significant increase in total bilirubin at early stage after TIPS(P= 0.001,OR=4.049);TATA box,enhancer c.-3279T> G,c.686C> A locus was not statistically different between the case group and the control group.3.After using binary logistic regression analysis to adjust preoperative total bilirubin,preoperative unconjugated bilirubin,preoperative alanine aminotransferase,preoperative Child-Pugh classification,preoperative MELD score and postoperative portal vein branch imaging factors,it was found that the population with c.211G> A AA/AG genotype increased the risk of increased total bilirubin early after TIPS(P= 0.005,OR = 5.609).Conclusion:1.c.211G> A locus gene polymorphism is associated with the occurrence of a increase in total bilirubin at early stage after TIPS.Individuals carrying allele A may have an increased risk of a significant increase in total bilirubin at early stage after TIPS;2.TATA box,enhancer c.-3279 T> G,c.686C> A site polymorphism There was no obvious correlation with the occurrence of a significant increase in total bilirubin at early stage after TIPS.