摘要:
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摘要:目的 探讨γ-谷氨酰转移酶(gamma-glutamyl transferase,GGT)、直接胆红素
(direct bilirubin,DBil)与胆囊收缩率在诊断胆道闭锁(biliary atresia,BA)中的应用
价值。方法 收集2017年9月至2021年9月在西安交通大学附属儿童医院及西安市中心医
院儿科住院治疗的185例胆汁淤积性肝病患儿为研究对象,根据剖腹探查或术中胆道
造影和随访情况,将患儿分为BA组(70例)和肝内胆汁淤积(intrahepatic cholestasis,
IHC)组(115例)。比较两组患儿的一般临床资料、实验室检查指标 [包括总胆红素
(total bilirubin,TBil)、DBil、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、
天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、GGT、碱性磷酸酶(alkaline
phosphatase,ALP)、总胆汁酸(total bile acid,TBA)] 及腹部超声检查资料。将有统
计学意义的指标纳入受试者工作特征(receiver operator characteristic,ROC)曲线分析,
计算ROC曲线下面积、最佳诊断界值和OR值;应用MedCalc软件进行ROC曲线下面积对
比,分析各指标对诊断BA的价值。结果 BA组和IHC组患儿的性别(男/女:31例/39例比
78例/37例)、就诊年龄(中位数:52.0 d比58.0 d)、肝脏肋下大小(中位数:4.0 cm比
2.0 cm)、脾大比例 [40%(28/70)比18.3%(21/115)]、大便颜色、TBil(中位数:
204.35 μmol/L比138.30 μmol/L)、DBil(中位数:125.70 μmol/L比80.00 μmol/L)、ALT
(中位数:112.00 U/L比71.00 U/L)、AST(中位数:175.00 U/L比120.00 U/L)、GGT
(中位数:440.75 U/L比 94.50 U/L)、餐后1 h胆囊收缩率(无收缩/有收缩且< 50%/
有收缩且> 50%:52.9% / 41.4% / 5.7%比7.0% / 27.8% / 65.2%)差异有统计学意义(P
均< 0.05)。两组患儿ALP(中位数526.00 U/L 比548.00 U/L)、TBA(中位数:143.45 μmol/L
比161.90 μmol/L)和25羟维生素D(中位数:8.00 ng/ml比8.13 ng/ml)水平差异无统计
学意义(P均> 0.05)。多因素Logistic回归分析表明,DBil(OR = 1.031,95% CI:
1.015~1.047,P < 0.001)、GGT(OR = 1.007,95% CI:1.004~1.011,P < 0.001)、
餐后1 h胆囊无收缩(OR = 57.493,95% CI:9.577~345.133,P < 0.001)和胆囊收缩
率< 50%(OR = 9.907,95% CI:1.828~53.710,P = 0.008)均为BA的危险因素。TBil、
DBil、ALT、AST、GGT、GGT + DBil、GGT + DBil +胆囊收缩率诊断BA的ROC曲线下
面积分别为0.797、0.820、0.614、0.658、0.890、0.932和0.963。单项指标中GGT的ROC曲
线下面积最大,当GGT超过界值173.20 U/L时诊断BA的敏感度、特异度、阳性似然比、
阴性似然比和诊断比值比分别为84.3%、78.3%、3.885、0.201和19.328。GGT + DBil + 胆
囊收缩率联合对BA的诊断价值最高,ROC曲线下面积显著高于GGT + DBil(z = 2.303,
P = 0.021),其诊断BA的敏感度、特异度、阳性似然比、阴性似然比和诊断比值比分别
为90.0%、90.4%、9.375、0.111和84.459。结论 GGT、DBil与胆囊收缩率联合对BA有较高
的诊断价值,当GGT超过界值173.20 U/L、DBil超过界值97.05 μmol/L且超声提示胆囊收缩
不良时需高度警惕BA。
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Abstract: Objective To investigate the value of gamma-glutamyl transferase (GGT), direct
bilirubin (DBil) and gallbladder contraction rate on the diagnosis of biliary atresia (BA).
Methods Total of 185 infants with cholestasis in the Children’s Hospital Affiliated to Xi’an
Jiaotong University and Xi’an Central Hospital from September 2017 to September 2021
were selected and divided into BA group (70 cases) and intrahepatic cholestasis (IHC)
group (115 cases) according to the results of exploratory laparotomy or intraoperative
cholangiography and follow-up. The general clinical data, laboratory examination [including
total bilirubin(TBil), DBil, alanine aminotransferase (ALT), aspartate aminotransferase
(AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and total bile
acid (TBA)] and abdominal ultrasonography data were compared between the two groups.
Receiver operating characteristic (ROC) curve was performed for indexes with statistical
significance. The area under the ROC curve, optimal cut-off value and odds ratio (OR) value
were calculated. MedCalc software was used to compare the area under the ROC curve
in the diagnosis of BA. Results Gender (male/female: 31 cases /39 cases vs. 78 cases /
37 cases), age (median: 52.0 d vs. 58.0 d), liver size (median: 4.0 cm vs. 2.0 cm), proportion
of splenomegaly [40% (28/70) vs. 18.3% (21/115)], stool color, TBil (median: 204.35 μmol/L vs.
138.30 μmol/L), DBil (median: 125.70 μmol/L vs. 80.00 μmol/L), ALT (median: 112.00 U/L vs.
71.00 U/L), AST (median: 175.00 U/L vs. 120.00 U/L), GGT (median: 440.75 U/L vs. 94.50 U/L)
and gallbladder contraction rate at 1 hour after meal (no contraction / contraction <
50% / contraction > 50%: 52.9% / 41.4% / 5.7% vs. 7.0% / 27.8% / 65.2%) of infants between
the two groups were statistically significant (all P < 0.05). There were no significant differences in
ALP (median: 526.00 U/L vs. 548.00 U/L), TBA (median: 143.45 μmol/L vs. 161.90 μmol/L) and
25 hydroxyvitamin D (median: 8.00 ng/ml vs. 8.13 ng/ml) levels of infants between the two groups
(all P > 0.05). Multivariate Logistic regression analysis showed that DBil (OR = 1.031, 95% CI:
1.015~1.047, P < 0.001), GGT (OR = 1.007, 95% CI: 1.004~1.011, P < 0.001), no gallbladder
contraction (OR = 57.493, 95% CI: 9.577~345.133, P < 0.001) and gallbladder contraction
rate < 50% at 1 hour after meal (OR = 9.907, 95% CI: 1.828~53.710, P = 0.008) were risk factors
for BA. The area under the ROC curve of TBil, DBil, ALT, AST, GGT, GGT + DBil, GGT +
DBil + gallbladder contraction rate were 0.797, 0.820, 0.614, 0.658, 0.890, 0.932 and 0.963,
respectively. In single index, GGT had the highest area under the ROC curve in the diagnosis of
BA. When GGT exceeded the cut-off value of 173.20 U/L, the sensitivity, specificity, positive
likelihood ratio, negative likelihood ratio and odds ratio of BA were 84.3%, 78.3%, 3.885, 0.201
and 19.328, respectively. Multiple indicators show that GGT + DBil + gallbladder contraction
rate had the highest value in the diagnosis of BA, which was significantly higher than that of GGT +
DBil (z = 2.303, P = 0.021), the sensitivity, specificity, positive likelihood ratio, negative
likelihood ratio and odds ratio were 90.0%, 90.4%, 9.375, 0.111 and 84.459, respectively.
Conclusions GGT + DBil + gallbladder contraction rate had a higher value in the diagnosis of
BA. If GGT and DBil exceed the cut-off value of 173.20 U/L and 97.05 μmol/L and ultrasound
suggested poor gallbladder contraction, BA should be highly vigilant.
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