UGT1A1基因突变对乙型肝炎慢加亚急性肝衰竭患者转归的影响

Effect of UGT1A1 Gene Mutation on the Outcome of Patients with Chronic Hepatitis B and Acute Liver Failure

目的探讨UGT1A1基因突变对乙型肝炎慢加亚急性肝衰竭患者(ACLF)转归的影响。方法该研究以福建医科大学孟超肝胆医院2015年5月-2017年10月期间入院后确诊的246例乙型肝炎慢加亚急性肝衰竭(ACLF)患者为研究对象。采取前瞻性研究方法,对246例ACLF患者进行UGT1A1基因测序。根据测序结果分为突变组(n=195)和无突变组(n=51),比较两组之间临床特征的差异。正态分布的计量资料组间比较采用t检验;偏态分布的计量资料组间比较采用Mann-Whitney U检验。计数资料组间比较用χ2检验。组间的不同时间的胆红素、MELD评分的采用广义线性混合效应模型分析(GLMMs)。采用χ2检验分析组间的生存率差异。结果①UGT1A1基因突变组与无突变患者基线临床特征基本相似,但突变组IBIL高于无突变组,差异有统计学意义(t=-1.976, P=0.05);②突变组与无突变组的TBIL、IBIL水平及MELD评分随时间变化差异有统计学意义(FTBIL=24.915,P=0.000;FIBIL=17.903,P=0.000;FMELD评分=8.179,P=0.000)。③突变组与无突变组患者生存率差异无统计学意义(P>0.05):慢性乙型肝炎基础上ACLF1期(100.00%vs 92.31%)(χ2=0.407,P=0.722)。慢性乙型肝炎基础上ACLF2期(76.92%vs76.47%)(χ2=0.973,P=0.643)。慢性乙型肝炎基础上ACLF3期(28.57%vs 31.58%)(χ2=0.022,P=0.639)。乙型肝炎肝硬化基础上ACLF1期(100.00%vs66.67%)(χ2=0.444,P=0.750)。乙型肝炎肝硬化基础上ACLF2期(57.89%vs 70.13%)(χ2=1.043,P=0.307)。乙型肝炎肝硬化基础上ACLF3期(80.00%vs 62.50%)(χ2=1.976,P=0.469)。结论①UGT1A1基因突变对乙型肝炎慢加亚急性肝衰竭患者的转归有一定影响,主要表现在胆红素代谢方面:突变组的胆红素上升的速度比无突变组快,消退较无突变组缓慢。②UGT1A1基因突变影响MELD评分,但对乙型肝炎慢加亚急性肝衰竭患者的生存率无明显影响。

Objective To investigate the effect of UGT1A1 gene mutation on the outcome of patients with chronic hepatitis B and acute acute liver failure (ACLF). Methods A total of 246 patients with hepatitis B chronic acute hepatic failure (ACLF) who were diagnosed after admission from May 2015 to October 2017 at Mengchao Hepatobiliary Hospital of Fujian Medical University were included in the study. A prospective study was conducted to sequence UGT1A1 genes in 246 patients with ACLF. According to the sequencing results, the mutation group (n=195) and the non-mutation group (n=51) were divided, and the differences in clinical characteristics between the two groups were compared. The t-test was used to compare the measurement data of the normal distribution;the Mann-Whitney U test was used to compare the measurement data of the skewed distribution. The chi-square test was used to compare the count data sets. The bilirubin and MELD scores at different times between groups were analyzed using generalized linear mixed-effects models (GLMMs). Chi-square test was used to analyze the difference in survival rates between groups. Results 1.The clinical features of the UGT1A1 gene mutation group were similar to those of the non-mutation group, but the IBIL of the mutation group was higher than that of the non-mutation group (t=-1.976, P=0.05). 2.The TBIL, IBIL levels and MELD scores over time of the mutation group and the non-mutation group were significantly different(FTBIL=24.915, P=0.000;FIBIL=17.903, P=0.000;FMELD score=8.179, P=0.000). 3.There was no significant difference in survival rate between the mutation group and the non-mutation group(P>0.05): chronic hepatitis B was based on ACLF1 stage (100.00% vs 92.31%)(χ2=0.407, P=0.722). Chronic hepatitis B was based on ACLF2(76.92% vs 76.47%)(χ2=0.973, P=0.643). Chronic hepatitis B was based on ACLF stage 3 (28.57% vs 31.58%)(χ2=0.022, P=0.639). Hepatitis B cirrhosis was based on ACLF1 (100.00% v 66.67%)(χ2=0.444, P=0.750). Hepatitis B cirrhosis was based on ACLF2 (57.89% vs 70.13%),(χ2=1.043, P=0.307). Hepatitis B cirrhosis was based on ACLF phase 3 (80.00% vs 62.50%)(χ2=1.976, P=0.469). Conclusion 1.UGT1A1 gene mutation has a certain effect on the outcome of patients with chronic hepatitis B and acute hepatic failure, mainly in the metabolism of bilirubin: the bilirubin in the mutant group rises faster than the non-mutant group, and the regression was slower than non-mutation group. 2.UGT1A1 gene mutation affects MELD score, but has no significant effect on the survival rate of patients with chronic hepatitis B and acute liver failure.