希特林蛋白缺乏症合并肝衰竭的相关因素分析

Analysis of related factors of citrin deficiency complicated with liver failure

目的分析影响希特林蛋白缺乏症(CD)合并肝衰竭(LF)的相关因素.方法回顾性分析2011年1月至2022年8月福建省儿童医院和福建省妇幼保健院儿内科收治的91例确诊为CD患儿的临床资料,其中28例合并LF(LF组),63例未合并LF(非LF组).收集患儿一般情况[性别、年龄、体质量、喂养方式和是否合并感染、是否大便颜色变浅、是否合并先天性心脏病、是否伴有肝脏增大]和实验室检查指标[白细胞计数(WBC)、中性粒细胞计数(NEU)、血红蛋白(Hb)、血小板计数(PLT)、C-反应蛋白(CRP)、血乳酸(Lac)、血氨、血钠、血钾、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、γ-谷氨酰转肽酶(γ-GGT)、总胆红素(TBil)、直接胆红素(DBil)、白蛋白、碱性磷酸酶(ALP)、胆汁酸、胆固醇、尿酸、肌酸激酶同工酶(CK-MB)、血糖(GLU)、凝血酶原时间(PT)、国际标准化比值(INR)]等临床资料.比较是否发生LF两组患儿上述临床指标的差异,将单因素分析差异有统计学意义的指标纳入多因素Logistic回归分析,寻找CD合并LF的相关因素;并绘制受试者工作特征曲线(ROC曲线)分析各因素对CD合并LF的预测价值;采用ROC曲线下面积(AUC)评估各因素对发生LF的预测效能.结果与非LF组比较,LF组合并感染比例(60.7%比12.7%)和TBil[μmol/L:242.50(210.95~278.68)比168.20(141.50~232.65)]和DBil[μmol/L:146.40(100.73~173.55)比79.40(65.39~99.60)]水平均更高,Hb(g/L:79.21±20.39比94.75±12.56)、PLT(×10^(9)/L:215.61±148.73比377.63±163.00)和GLU(mmol/L:2.79±1.32比4.10±1.36)水平均更低,预后更差[病死率:15.0%(3/28)比0.0%(0/63)],差异均有统计学意义(均P<0.05).多因素Logistic回归分析显示,合并感染[优势比(OR)=5.160,95%可信区间(95%CI)为1.006~26.455,P=0.049]、Hb(OR=0.930,95%CI为0.869~0.996,P=0.037)、PLT(OR=0.992,95%CI为0.987~0.998,P=0.009)、GLU(OR=0.355,95%CI为0.174~0.724,P=0.004)下降和TBil(OR=1.016,95%CI为1.001~1.030,P=0.034)升高是CD合并LF的相关影响因素.ROC曲线分析显示:Hb、PLT、GLU、TBil和联合检测对CD合并LF均有一定预测价值[AUC和95%CI分别为0.754(0.639~0.868)、0.756(0.646~0.867)、0.749(0.644~0.854)、0.807(0.717~0.898)和0.944(0.897~0.992),P值均为0.000],其中联合诊断的效能最高;当Hb、PLT、GLU、TBil的最佳截断值分别为86.50 g/L、254.50×10^(9)/L、3.29 mmol/L、185.40μmol/L时,其敏感度分别为74.6%、81.0%、76.2%、96.4%,特异度分别为71.4%、63.3%、64.3%、65.1%.结论合并感染、下降的Hb、PLT、GLU和升高的TBil均是CD合并LF的相关影响因素,联合诊断可以提高诊断效能.

Objective To investigate the related factors of citrin deficiency(CD)complicated with liver failure(LF).Methods A retrospective analysis was performed on 91 patients with CD admitted to the department of pediatrics of Fujian Children's Hospital and Fujian Maternity and Child Health Hospital from January 2011 to August 2022,including 28 patients with LF(LF group)and 63 patients without LF(non-LF group).The general information of the patients(gender,age,body weight,feeding method and whether they were co-infected,whether they had light-colored stool,whether they had congenital heart disease,and whether they were accompanied by hepatomegaly)and laboratory indicators of the patients[white blood cell count(WBC),neutrophil count(NEU),hemoglobin(Hb),platelet count(PLT),C-reactive protein(CRP),blood lactic acid(Lac),blood ammonia,blood sodium,blood potassium,alanine aminotransferase(ALT),aspartate aminotransferase(AST),γ-glutamyl transpeptides(γ-GGT),total bilirubin(TBi1),direct bilirubin(DBil),albumin,alkaline phosphatase(ALP),bile acid,cholesterol,uric acid,MB isoenzyme of creatine kinase(CK-MB),blood glucose(GLU),prothrombin time(PT),international standard normalized ratio(INR)were collected.The above indicators in two groups were compared,and the indicators with statistically significant differences in univariate analysis were included in Logistic regression analysis to find the correlated factors of CD complicated with LF.The predictive value of each related factor for CD complicated with LF was analyzed by drawing receiver operator characteristic curve(ROC curve).The area under the ROC curve(AUC)was used to evaluate the prediction efficiency of each factor.Results Compared with non-LF group,the patients in LF group had higher proportion of infections(60.7%vs.12.7%),higher TBil[μmol/L:242.50(210.95-278.68)vs.168.20(141.50-232.65)]and DBil[umol/L:146.40(100.73-173.55)vs.79.40(65.39-99.60)],lower Hb(g/L:79.21±20.39 vs.94.75±12.56),PLT(×10^(9)/L:215.61±148.73 vs.377.63±163.00)and CLU(mmol/L:2.79±1.32 vs.4.10±1.36),worse prognosis[mortality:15.0%(3/28)vs.0.0%(0/63)],the differences were statistically significant(all P<0.05).Logistic regression multi-factor analysis showed infections[odds ratio(0R)=5.160,95%credibility interval(95%CI)was 1.006-26.455,P=0.049],decreased Hb(OR=0.930,95%CI was 0.869-0.996,P=0.037),decreased PLT(OR=0.992,95%CI was 0.987-0.998,P=0.009),decreased GLU(OR=0.355,95%CI was 0.174-0.724,P=0.004)and increased TBil(OR=1.016,95%CI was 1.001-1.030,P=0.034)were the related factors of CD complicated with LF.ROC curve analysis showed that Hb,PLT,GLU,TBil and the combined diagnosis had certain predictive value for CD complicated with LF[AUC and 95%CI were 0.754(0.639-0.868),0.756(0.646-0.867),0.749(0.644-0.854),0.807(0.717-0.898)and 0.944(0.897-0.992),respectively,all P=O.000j,among them,the combined diagnostic efficiency was the highest.When the best cut-off values of Hb,PLT,CLU and TBil were 86.50 g/L,254.50×10^(9)/L,3.29 mmol/L and 185.40μmol/L,the sensitivity of Hb,PLT,GLU and TBiL were 74.6%,81.0%,76.2%and 96.4%,respectively,the specificity were 71.4%,63.3%,64.3%and 65.1%,respectively.Conclusion Infections,decreased Hb,PLT,GLU and increased TBil are the related factors associated with LF in CD,and combined diagnosis can improve the diagnostic efficiency.