Abstract:

Objective　To analyze the expressions and clinical significance of chemokine ligand 12 and its receptor 4 (CXCL12/CXCR4) in children with biliary atresia liver fibrosis. Methods　A total of 100 children with biliary atresia liver fibrosis admitted to Baoji Maternal and Child Health Hospital from May 2019 to May 2024 were selected as the study group, and the fibrosis grades were performed, including 36 cases of grade Ⅰ-Ⅱ and 64 cases of grade Ⅲ-Ⅳ. Forty-five children with common bile duct cysts admitted for surgery during the same period were selected as the control group. There were 47 males and 53 females in the study group, aged (59.41±5.23) d. There were 22 males and 23 females in the control group, aged (60.33±5.48) d. The general data [gender, age, white blood cell count (WBC), platelet count (PLT), and neutrophil to lymphocyte ratio (NLR)], expression levels of CXCL12 and CXCR4 protein, and liver function indexes [alanine aminotransferase (ALT), total bilirubin (TBil), and glutamyl transpeptidase (GGT)] of the two groups were compared. And the expression levels of CXCL12 and CXCR4 protein in children with biliary atresia liver fibrosis of different fibrosis grades. Independent sample t test and χ² test were used for statistical analysis. Multivariate logistic regression analysis was used to analyze the influencing factors of biliary atresia liver fibrosis. The receiver operating characteristic curve (ROC) was used to analyze the diagnostic efficiency of each index for biliary atresia liver fibrosis, and the area under the curve (AUC) was calculated. The correlations between the expression levels of CXCL12 and CXCR4 protein and the grade of fibrosis in children with biliary atresia liver fibrosis were analyzed by scatter plot. Results　The expression levels of CXCL12 and CXCR4 protein in the study group were higher than those in the control group [(1.09±0.26) μg/L vs. (0.89±0.18) μg/L, (1.04±0.22) μg/L vs. (0.87±0.19) μg/L] (both P<0.05). Serum ALT, TBil, and GGT levels in the study group were higher than those in the control group [(75.47±23.12) U/L vs. (62.15±10.33) U/L, (148.26±30.14) μmol/L vs. (125.27±28.59) μmol/L, (321.87±43.26) U/L vs. (285.49±38.15) U/L] (all P<0.05). Multiple logistic regression analysis showed that CXCL12 and CXCR4 protein expression levels and serum ALT, TBil, and GGT levels were independent risk factors for biliary atresia liver fibrosis (all P<0.05). ROC results showed that the AUC of CXCL12 and CXCR4 protein expression levels combined with serum ALT, TBil, and GGT in the diagnosis of biliary atresia liver fibrosis was greater than those of single index (0.874 vs. 0.670, 0.642, 0.693, 0.677, and 0.720) (all P<0.05). The expression levels of CXCL12 and CXCR4 protein in children with biliary atresia liver fibrosis in grade Ⅲ-Ⅳ were higher than those in grade Ⅰ-Ⅱ [(1.54±0.20) μg/L vs. (1.07±0.17) μg/L, (1.14±0.10) μg/L vs. (0.91±0.07) μg/L] (both P<0.05). Correlation analysis showed that the expression levels of CXCL12 and CXCR4 protein were positively correlated with fibrosis grade in children with biliary atresia liver fibrosis (both P<0.05). Conclusions　The combined diagnosis of CXCL12, CXCR4, ALT, TBil, and GGT has good diagnostic value for biliary atresia liver fibrosis. CXCL12 and CXCR4 are positively correlated with fibrosis grading, and clinical studies can use CXCL12 and CXCR4 as specific indicators for liver fibrosis in children with biliary atresia.

Key words:

Biliary atresia liver fibrosis, Children, Chemokine ligand 12, Chemokine receptor 4, Expression, Clinical significance

摘要：

目的　分析趋化因子配体12（CXCL12）及趋化因子受体4（CXCR4）在儿童胆道闭锁肝纤维化中的表达情况和临床意义。方法　选取2019年5月至2024年5月宝鸡市妇幼保健院收治的100例胆道闭锁肝纤维化患儿为研究组，并对患儿进行纤维化分级，Ⅰ～Ⅱ级36例，Ⅲ～Ⅳ级64例。选取同期入院手术的45例胆总管囊肿患儿为对照组。研究组男47例，女53例；年龄（59.41±5.23）d。对照组男22例，女23例；年龄（60.33±5.48）d。比较两组一般资料［性别、年龄、白细胞计数（WBC）、血小板计数（PLT）、中性粒细胞与淋巴细胞比值（NLR）］、CXCL12及CXCR4蛋白表达水平、肝功能指标［谷丙转氨酶（ALT）、总胆红素（TBil）、谷氨酰转肽酶（GGT）］，不同纤维化分级胆道闭锁肝纤维化患儿CXCL12、CXCR4蛋白表达水平。采用独立样本t检验和χ²检验进行统计学分析。采用多因素logistic回归分析胆道闭锁肝纤维化的影响因素。采用受试者操作特征曲线（ROC）分析各指标对胆道闭锁肝纤维化的诊断效能，计算曲线下面积（AUC）。采用散点图分析胆道闭锁肝纤维化患儿CXCL12、CXCR4蛋白表达水平与纤维化分级的相关性。结果　研究组CXCL12、CXCR4蛋白表达水平均高于对照组［（1.09±0.26）μg/L比（0.89±0.18）μg/L、（1.04±0.22）μg/L比（0.87±0.19）μg/L］（均P<0.05）。研究组血清ALT、TBil、GGT水平均高于对照组［（75.47±23.12）U/L比（62.15±10.33）U/L、（148.26±30.14）μmol/L比（125.27±28.59）μmol/L、（321.87±43.26）U/L比（285.49±38.15）U/L］（均P<0.05）。多因素logistic回归分析显示，CXCL12、CXCR4蛋白表达水平和血清ALT、TBil、GGT水平均是胆道闭锁肝纤维化的独立危险因素（均P<0.05）。ROC结果显示，CXCL12、CXCR4蛋白表达水平和血清ALT、TBil、GGT水平联合诊断胆道闭锁肝纤维化的AUC大于单一指标（0.874比0.670、0.642、0.693、0.677、0.720）（均P<0.05）。Ⅲ～Ⅳ级胆道闭锁肝纤维化患儿CXCL12、CXCR4蛋白表达水平均高于Ⅰ～Ⅱ级［（1.54±0.20）μg/L比（1.07±0.17）μg/L、（1.14±0.10）μg/L比（0.91±0.07）μg/L］（均P<0.05）。相关性分析显示，胆道闭锁肝纤维化患儿CXCL12、CXCR4蛋白表达水平与纤维化分级呈正相关（均P<0.05）。结论　CXCL12、CXCR4蛋白表达水平和血清ALT、TBil、GGT水平联合诊断胆道闭锁肝纤维化价值较高，CXCL12、CXCR4蛋白表达水平与纤维化分级呈正相关，临床可将CXCL12、CXCR4蛋白表达水平作为胆道闭锁肝纤维化患儿特异性指标进行研究。

关键词:

胆道闭锁肝纤维化, 儿童, 趋化因子配体12, 趋化因子受体4, 表达情况, 临床意义