Tong Mingxin,Xie Hua,Tang Weibing,et al.Integrated pre-and post-natal differential diagnosis of cystic biliary atresia[J].Journal of Clinical Pediatric Surgery,2024,(12):1125-1132.[doi:10.3760/cma.j.cn101785-202403047-004]
囊肿型胆道闭锁的产前产后一体化鉴别诊断
- Title:
- Integrated pre-and post-natal differential diagnosis of cystic biliary atresia
- Keywords:
- Cystic Biliary Atresia; Choledochal Cyst; Diagnosis; Differential; Prenatal Diagnosis; Ultrasonography; Prenatal; Postpartum Period; Diagnosis; Conjugated Bilirubin; Total Bile Acid; Infant; Newborn
- 摘要:
- 目的 囊肿型胆道闭锁(cystic biliary atresia,CBA)是产前通过超声检查可发现的特殊类型胆道闭锁(biliary atresia,BA),容易与胆总管囊肿(choledochal cyst,CC)相混淆,二者早期鉴别诊断存在一定困难。本研究旨在探讨CBA与CC患儿产前超声影像特征、出生后2周内结合胆红素(conjugated bilirubin,CB)及总胆汁酸(total bile acid,TBA)水平对于CBA和CC的鉴别诊断价值。方法 本研究为多中心回顾性研究。收集2020年10月至2021年12月中国大陆13个儿科研究中心产前发现的肝门区囊肿新生儿作为研究对象,收集所有入选新生儿的产前超声检查结果,并于出生后2周内每周检测血CB和TBA水平各1次。根据手术结果或最终临床结局将患儿分为CBA组和CC组,对比两组产前超声影像特征以及出生后2周内CB和TBA的差异,并通过统计分析评估上述指标对于CBA和CC的鉴别诊断效能及临界值。结果 共143例产前发现肝门区囊肿的患儿纳入研究,其中CBA组37例,CC组106例,初始诊断时间为孕(25.29±6.07)周。两组囊肿初始体积和直径差异无统计学意义(P＞0.05)。CC组囊肿体积增长速度显著高于CBA组,至产前末次超声检查时,CC组囊肿体积平均增长8.34倍,而CBA组仅增长1.48倍。当囊肿体积增长临界值设为3.90倍时,诊断CBA的AUC、灵敏度分别为0.828(95%CI:0.728~0.929)、83.3%。CBA组患儿的CB和TBA水平自出生后第1周开始显著升高,第2周继续升高。当出生后第1周CB(CB1)临界值为24 μmol/L、出生后第2周TBA(TBA2)临界值为20.9 μmol/L时,鉴别诊断CBA和CC的约登指数达到最大值,分别为0.880和0.826,对应AUC分别为0.902和0.860。结论 经系列产前超声检查提示囊肿体积增加倍数＜3.90的新生儿患CBA的风险较高。胆囊形态异常对于CBA的产前诊断有重要意义。出生后2周内CB和TBA水平可用于鉴别诊断CBA和CC,当CB1≥24 μmol/L和TBA2≥20.9 μmol/L时,提示CBA的患病风险较高。
- Abstract:
- Objective Cystic Biliary Atresia (CBA) is a special type of Biliary Atresia (BA) that can be detected prenatally through ultrasound examination.It is easily confused with Choledochal Cyst (CC),and there is a certain challenge in differentiating between the two in early diagnosis.The purpose of this study is to explore the differences in prenatal ultrasonic imaging characteristics between CBA and CC cases,and to evaluate the value of conjugated bilirubin (CB) and total bile acid (TBA) levels in the early postnatal period (i.e.,within the first 2 weeks after birth) for the differential diagnosis of these two conditions. Methods This is a retrospective multicenter clinical study.The patients were divided into CBA group and CC group according to surgical outcome or final clinical outcome.The prenatal ultrasound image characteristics and the differences in CB and TBA values between the two groups were compared,and the diagnostic efficacy and cut-off value of these indicators in differentiating CBA and CC were evaluated by statistical analysis. Results A total of 143 children with hepatic portal cysts were included in this study,including 37 in the CBA group and 106 in the CC group.The mean time of initial diagnosis was (25.29±6.07) weeks of gestation.There was no difference in the initial volume and diameter of cysts between the two groups.However,the growth rate of cysts in the CC group was significantly higher than that in the CBA group.The average growth rate of cysts in the CC group was 8.34 times at the last prenatal ultrasound examination,while that in the CBA group was only 1.48 times.When the critical value of cyst volume growth was set to 3.90 times,the AUC and sensitivity for diagnosing CBA were 0.828 (95%CI,0.728-0.929) and 83.3%,respectively.In addition,CB and TBA levels in the CBA group increased significantly from the first week after birth and continued to increase at the second week.When the critical value of CB1 was 24 μmol/L,and the critical value of TBA2 was 20.9 μmol/L,the Jorden index of CBA and CC reached the maximum value,which were 0.880 and 0.826,and the corresponding AUC were 0.902 and 0.860,respectively. Conclusions A series of prenatal ultrasonography indicated that newborns with a cyst volume increase of < 3.90 had a higher risk of CBA.In addition,abnormal gallbladder morphology is important for the prenatal diagnosis of CBA.CB and TBA within 2 weeks of birth can be used to distinguish CBA from CC.CB1≥24 μmol/L and TBA2≥20.9 μmol/L suggest a higher risk of CBA.
参考文献/References:
[1] Hartley JL,Davenport M,Kelly DA.Biliary atresia[J].Lancet,2009,374(9702):1704-1713.DOI:10.1016/S0140-6736(09)60946-6.
[2] Bezerra JA,Wells RG,Mack CL,et al.Biliary atresia:clinical and research challenges for the Twenty-First century[J].Hepatology,2018,68(3):1163-1173.DOI:10.1002/hep.29905.
[3] Chung PHY,Zheng S,Tam PKH.Biliary atresia:east versus west[J].Semin Pediatr Surg,2020,29(4):150950.DOI:10.1016/j.sempedsurg.2020.150950.
[4] Serinet MO,Wildhaber BE,Broué P,et al.Impact of age at Kasai operation on its results in late childhood and adolescence:a rational basis for biliary atresia screening[J].Pediatrics,2009,123(5):1280-1286.DOI:10.1542/peds.2008-1949.
[5] Lakshminarayanan B,Davenport M.Biliary atresia:A comprehensive review[J].Autoimmun,2016,73:1-9.DOI:10.1016/j.jaut.2016.06.005.
[6] Scottoni F,Davenport M.Biliary atresia:potential for a new decade[J].Semin Pediatr Surg,2020,29(4):150940.DOI:10.1016/j.sempedsurg.2020.150940.
[7] Casaccia G,Bilancioni E,Nahom A,et al.Cystic anomalies of biliary tree in the fetus:is it possible to make a more specific prenatal diagnosis?[J].J Pediatr Surg,2002,37(8):1191-1194.DOI:10.1053/jpsu.2002.34470.
[8] Yang D,Li L,Diao M,et al.Prenatal diagnosis at different gestational times and clinical features of choledochal cysts:a single tertiary center report[J].Pediatr Surg Int,2023,39(1):105.DOI:10.1007/s00383-023-05374-5.
[9] Shin HJ,Yoon H,Han SJ,et al.Key imaging features for differentiating cystic biliary atresia from choledochal cyst:prenatal ultrasonography and postnatal ultrasonography and MRI[J].Ultrasonography,2021,40(2):301-311.DOI:10.14366/usg.20061.
[10] Yu P,Dong N,Pan YK,et al.Comparison between cystic biliary atresia and choledochal cyst:a clinical controlled study[J].Pediatr Surg Int,2022,38(1):109-114.DOI:10.1007/s00383-021-05004-y.
[11] Caponcelli E,Knisely AS,Davenport M.Cystic biliary atresia:an etiologic and prognostic subgroup[J].J Pediatr Surg,2008,43(9):1619-1624.DOI:10.1016/j.jpedsurg.2007.12.058.
[12] Harpavat S,Garcia-Prats JA,Anaya C,et al.Diagnostic yield of newborn screening for biliary atresia using direct or conjugated bilirubin measurements[J].JAMA,2020,323(12):1141-1150.DOI:10.1001/jama.2020.0837.
[13] Harpavat S,Garcia-Prats JA,Shneider BL.Newborn bilirubin screening for biliary atresia[J].N Engl J Med,2016,375(6):605-606.DOI:10.1056/NEJMc1601230.
[14] Harpavat S,Finegold MJ,Karpen SJ.Patients with biliary atresia have elevated direct/conjugated bilirubin levels shortly after birth[J].Pediatrics,2011,128(6):e1428-e1433.DOI:10.1542/peds.2011-1869.
[15] Gong ZH,Wu YB,Zheng LL,et al.Can free carnitine or bilirubin in blood be used in neonatal screening for biliary atresia?[J].Eur J Pediatr Surg,2020,30(5):459-464.DOI:10.1055/s-0039-1698764.
[16] Noorulla F,Dedon R,Maisels MJ.Association of early direct bilirubin levels and biliary atresia among neonates[J].JAMA Netw Open,2019,2(10):e1913321.DOI:10.1001/jamanetworkopen.2019.13321.
[17] Kastenberg ZJ,Deneau MR,O’Brien EA,et al.Fractionated bilirubin among 252 892 Utah newborns with and without biliary atresia:a 15-year historical birth cohort study[J].J Pediatr,2023,257:113339.DOI:10.1016/j.jpeds.2022.12.041.
[18] Hoshino E,Moriwaki K,Morimoto K,et al.Cost-effectiveness analysis of universal screening for biliary atresia in Japan[J].J Pediatr,2023,253:101-106.e2.DOI:10.1016/j.jpeds.2022.09.028.
[19] Zhou KJ,Lin N,Xiao YT,et al.Elevated bile acids in newborns with Biliary Atresia (BA)[J].PLoS One,2012,7(11):e49270.DOI:10.1371/journal.pone.0049270.
[20] Chen LZ,He FJ,Zeng KH,et al.Differentiation of cystic biliary atresia and choledochal cysts using prenatal ultrasonography[J].Ultrasonography,2022,41(1):140-149.DOI:10.14366/usg.21028.
[21] 詹江华,余晨.胆道闭锁发病机制研究概述与启示[J].临床小儿外科杂志,2018,17(11):801-804.DOI:10.3969/j.issn.1671-6353.2018.11.001. Zhan JH,Yu C.An overview and enlightenment of the pathogenesis of biliary atresia[J].DOI:10.3969/j.issn.1671-6353.2018.11.001.
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备注/Memo
收稿日期:2024-3-25。
基金项目:国家自然科学基金(82170529)
通讯作者:冯杰雄,Email:fengjiexiong@126.com;张志波,Email:zhangzb@sj-hospital.org