Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.
目的： 探讨经颈静脉肝内门体分流术（TIPS）后早期总胆红素升高的影响因素及其与UGT1A1基因多态性的相关性。 方法： 以104例门静脉高压食管胃静脉曲张破裂出血(EVB)择期TIPS治疗的患者为研究对象，依据术后早期总胆红素升高水平分为胆红素升高组和胆红素正常组，采用单因素分析和logistic回归分析术后早期总胆红素升高的影响因素。利用PCR扩增和第一代测序技术对UGT1A1基因启动子区TATA box、增强子c.-3279 T > G、c.211G > A、c.686C > A四个基因多态性位点进行检测，logistic回归分析四个位点等位基因和基因型与术后早期总胆红素升高的相关性。 结果： 104例患者，胆红素升高组47例，其中男性35例（74.5%），女性12例（25.5%），年龄（50.72±12.56）岁。胆红素正常组57例，其中男性42例（73.7%），女性15例（26.3%），年龄（51.63±11.10）岁。2组患者年龄（t = -0.391，P = 0.697）和性别（χ(2) = 0.008，P = 0.928）差异均无统计学意义。单因素分析发现术前丙氨酸转氨酶（ALT）水平（χ(2) = 5.954，P = 0.015）、总胆红素水平（χ(2) = 16.638，P < 0.001）、终末期肝病模型（MELD）评分（χ(2) = 10.054，P = 0.018）、Child-Pugh分级（χ(2) = 6.844，P = 0.022）及术后门静脉分支显影情况（χ(2) = 6.738，P = 0.034）在2组间差异均有统计学意义。Logistic回归分析显示术前ALT水平、总胆红素水平、TIPS术后门静脉分支显影情况与术后早期总胆红素升高相关。UGT1A1基因c.211G > A位点基因多态性与TIPS术后早期总胆红素升高相关，携带等位基因A的人群发生术后早期总胆红素升高的风险增加（P = 0.001，OR = 4.049）；启动子区TATA box、增强子c.-3279 T > G、c.686C > A位点的等位基因多态性在胆红素升高组与胆红素正常组间差异均无统计学意义。 结论： 患者术前ALT水平、总胆红素水平、门静脉造影分支显影情况与术后早期总胆红素升高相关。UGT1A1基因增强子c.211G > A基因多态性与TIPS术后早期总胆红素升高的发生相关，携带等位基因A个体术后早期发生总胆红素升高的风险有可能增加。.
Keywords: Esophago-gas-tric fundal varices; Esophagogasstric variceal bleeding; Gene polymorphism; Transjugular intrahepatic portosystemic shunt; Uridine diphosphate glucuronyl transferases 1A1.