先天性胆道闭锁的早期诊断研究进展

先天性胆道闭锁是新生儿胆汁淤积症最常见的病因,也是小儿肝移植的主要指征,如果不及时诊治,可导致患儿进行性肝纤维化、胆汁淤积性肝硬化甚至死亡。目前普遍认为及时行Kasai术或肝移植可明显改善先天性胆道闭锁患儿预后,因此其早期鉴别诊断极其重要。然而,先天性胆道闭锁与其他原因引起的新生儿胆汁淤积症早期在临床表现、实验室检查以及影像学特征方面存在着诸多共同点,给临床鉴别诊断带来极大困难。过去的十年里,各种无创性检查诊断先天性胆道闭锁取得了很大进展,包括早期筛查,特征性生物标志物的研发,超声检查定性、定量指标的完善,放射性核素肝胆动态显像价值所在的明确,经内镜逆行胰胆管造影术及磁共振胰胆管造影应用的探索等。但目前临床上尚无一种同时具有高敏感性和特异性的无创性早期鉴别诊断先天性胆道闭锁的方法。术中胆道探查、造影仍是目前诊断先天性胆道闭锁的最准确的方法,但该法的有创性及对术者的高要求限制了其在临床上的应用。本综述在阐述临床常用早期鉴别诊断先天性胆道闭锁方法特点的基础上,进一步探索了多学科、多技术联合应用早期鉴别诊断先天性胆道闭锁的最佳策略,为提高先天性胆道闭锁早期鉴别诊断的敏感性、特异性提供参考。      

Biliary atresia associated with meconium peritonitis

Biliary atresia, malrotation, meconium peritonitis and transient hypothyroidism are occasionally seen in neonatal infants. Biliary atresia associated with malrotation has been reported in some patients with polysplenia syndrome, but biliary atresia associated with meconium peritonitis has only been described by a few investigators. Here we present a case of meconium peritonitis due to malrotation with volvulus, followed by biliary atresia and transient hypothyroidism during early infancy.     

小儿胆道闭锁症诊断与处理的改进

回顾了4年来18例胆道闭锁症的诊断与处理。指出以十二指肠引流液胆红素及胆酸测定鉴别胆道闭锁症与新生儿肝炎简便易行,可以缩短术前诊断时间。术中使用稀释美兰胆道造影代替X线胆道造影也可以了解肝外胆道的形态。作葛西手术时适当切断肝脏冠状和镰状韧带托出肝脏,在腹腔外解剖肝门可以降低手术的难度,便于完成肝门肠吻合操作。     

Characteristics of Malaysian infants with biliary atresia and neonatal hepatitis

Cholestatic disorders of infancy (viz neonatal hepatitis and biliary atresia) have not been well studied in Malaysia. In a retrospective study in the Department of Paediatrics, University Hospital, Kuala Lumpur from January 1982 through December 1991, a total of ninety-three infants with such conditions were identified: 35 (38%) had biliary atresia, 58 (62%) neonatal hepatitis. There was a statistically significant male preponderance in the neonatal hepatitis group (P = 0.020). There was no significant difference in the racial distribution and in the proportions of low birthweight infants between the two groups of disorders. When the biliary atresia group was compared with the neonatal hepatitis group, significant differences were observed in the age of presentation (mean +/- SD) 9.8 +/- 6.8 VS 20 +/- 17.3 weeks (P < 0.001), proportion of infants with prolonged jaundice (> seven weeks) 28/35 (80%) VS 20/58 (34.5%) (P < 0.00001), occurrence of alcoholic stools 26/35 (74.3%) VS 27/58 (46.6%) (P = 0.020), liver size (mean +/- SD): 4.3 (1.6 cm VS 3.3 +/- 1.8 cm (P < 0.01) and splenic size: 2.5 (1.8 cm VS 1.4 (1.2 cm (P < 0.001). There was however considerable overlap between the two groups in these features at presentation, making clinical differentiation between the two conditions difficult. Infants with cholestasis tended to present late, compromising the chance of survival. In order to improve the medical care of these patients, these conditions must be emphasised during the training of medical practitioners, and efforts to increase public awareness of these conditions must be created.     

Bile acid metabolism in extrahepatic biliary atresia: lithocholic acid in stored dried blood collected at neonatal screening

Lithocholic acid (LCA) is a potent hepatotoxic compound. Fetal LCA may have a role in the pathogenesis of neonatal cholestasis/extrahepatic biliary atresia (EHBA). Fetal liver efficiently hydroxylates LCA in several positions. This may represent a detox-ification mechanism. In the present study LCA, cholic acid (CA) and chenodeoxycholic acid (CDCA) were quantitated by gas chromatography-mass spectrometry using selected ion monitoring in small amounts of stored dried blood from six newborn infants with EHBA and fourteen con-trols. The blood was collected at neonatal metabolic screening. Mean blood levels (+/- S.E.M.) of LCA were 0.11 +/- 0.04 microM in the in-fants with EHBA and 0.08 +/- 0.02 microM in the control infants. The correspon-ding levels for CA and CDCA were 15.6 +/- 3.6 microM and 7.4 +/- 2.5 microM in the infants with EHBA and 1.7 +/- 0.3 microM and 1.8 +/- 0.4 microM in the controls. The increased levels of CA and CDCA in the infants with liver disease can be explained by cholestasis. The low blood levels of LCA indicate a normal fetal metabolism of this bile acid in EHBA.     

Biliary atresia--translational research on key molecular processes regulating biliary injury and obstruction

Biliary atresia is the most common cause of pathologic jaundice in young infants and results from the obstruction of the extrahepatic bile ducts by an inflammatory and fibro-obliterative process. Although the pathogenesis of the disease is multifactorial, recent patient- and animal-based studies began deciphering the molecular pathways involved in biliary injury and duct obstruction. Using large-scale genomics and immunostaining of livers from children with biliary atresia, investigators have discovered unique molecular signatures of dominant proinflammatory cytokines at the time of diagnosis. To study hypotheses generated from these patient-based studies, the anatomical and inflammatory profiles of a mouse model of rotavirus-induced biliary atresia were analyzed and found to share striking similarities with the human profiles. Then, using these mice in mechanistic studies, interferon-gamma (IFNgamma) has been shown to regulate the biliary tropism of lymphocytes to the biliary system, and to play a critical role in the inflammatory obstruction of extrahepatic bile ducts. The ability to combine human studies with a laboratory model of neonatal biliary injury and obstruction opens a new era of opportunities to advance the field of biliary atresia, and to develop new therapeutic strategies to improve long-term outcome with the native liver of children with biliary atresia.     

110例胆道闭锁患儿临床资料分析

目的 回顾性分析110例胆道闭锁患儿的临床特征以为胆道闭锁的诊断和治疗提供更多证据.方法 收集2017年8月至2020年8月期间在深圳市儿童医院收治的110例胆道闭锁患儿的临床资料,对患儿的一般资料和实验室检查资料进行总结分析.结果 本研究纳入的110例胆道闭锁患儿中,男49例(39％),女67例(61％).在所有患儿...     

胆道闭锁和新生儿肝炎肝脏的电镜观察

对6例胆道闭锁患儿和3例新生儿肝炎患儿肝脏进行了透射电镜的观察。发现胆道闭锁患儿肝细胞质内高电子密度物质(EDM)较新生儿肝炎患儿为多。认为其与胆汁淤滞有密切关系。推测其为胆色素性物质。胆道闭锁患儿毛细胆管数量较新生儿肝炎患儿为多,管腔稍有扩张。还可见到胆道闭锁患儿毛细胆管处细胞连接破坏现象。这些可能是胆管梗阻,胆管内压增高所致。     

Bile Acid Metabolism in Extrahepatic Biliary Atresia

Lithocholic acid (LCA) is a potent hepatotoxic compound. Fetal LCA may have a role in the pathogenesis of neonatal cholestasis/extrahepatic biliary atresia (EHBA). Fetal liver efficiently hydroxylates LCA in several positions. This may represent a detox-ification mechanism. In the present study LCA, cholic acid (CA) and chenodeoxycholic acid (CDCA) were quantitated by gas chromatography-mass spectrometry using selected ion monitoring in small amounts of stored dried blood from six newborn infants with EHBA and fourteen con-trols. The blood was collected at neonatal metabolic screening. Mean blood levels (±S.E.M.) of LCA were 0.11±0.04 μM in the in-fants with EHBA and 0.08±0.02 μM in the control infants. The corresponding levels for CA and CDCA were 15.6±3.6 μM and 7.4±2.5 μM in the infants with EHBA and 1.7±0.3 μM and 1.8±0.4 μM in the controls. The increased levels of CA and CDCA in the infants with liver disease can be explained by cholestasis. The low blood levels of LCA indicate a normal fetal metabolism of this bile acid in EHBA.     

彩色多普勒超声对婴儿外科性黄疸的诊断价值

目的在婴儿期有多种引起黄疸的肝胆外科疾病,本研究通过术前对胆道闭锁、先天性胆总管囊肿等疾病声像图形态特点及血供的观察,探讨彩色多普勒超声显像在婴儿外科性黄疸鉴别诊断中的应用价值.方法二维超声观察肝脏、胆囊及胆管的形态大小,彩色多普勒超声观察门静脉及肝动脉的血流并鉴别肝动脉及胆管结构.结果手术治疗胆道闭锁20例,超声术前诊断18例;先天性胆总管囊肿16例,超声术前诊断16例.胆道闭锁术前超声显示肝脏肿大,胆囊细小且壁增厚,肝门部三角形高回声块,门静脉流速减慢,肝动脉流速增快,阻力指数增大.先天性胆总管囊肿超声显示胆总管部位囊性包块.结论彩色多普勒超声对婴儿外科性黄疸常见病因的早期诊断、鉴别诊断与指导治疗均有重要的应用价值.     

婴儿胆汁淤积症88例临床研究

目的探讨婴儿胆汁淤积症的临床特点和诊断方法。方法收集我科2009-2011年收治的88例胆汁淤积症患儿,对其病因、临床检查、病理及预后进行分析。结果婴儿胆汁淤积症男孩、足月儿多见;2~3月龄发病率高。本组患儿中胆道闭锁组19例;肝内淤胆组69例,其中仅10.1%明确病因。胆道闭锁组γ谷氨酰转肽酶(GGT)水平明显高于肝内淤胆组,其他生化指标差异无统计学意义。血筛瓜氨酸血症1例;尿筛40%患儿高度怀疑Citrin缺陷。肝内淤胆组中23例行LSC25A13基因12种突变位点的检测,结果均为阴性。胆道闭锁组B超确诊率为64.7%。49例肝组织病理提示两组胆汁性肝硬化发生率差异有统计学意义(P<0.01)。两组的病死率和好转痊愈率差异有统计学意义(P<0.01)。结论胆道造影术、内科动态观察是鉴别胆道闭锁的常用方法,前者更可靠。对于有肝内胆汁淤积病史或存在肝功能反复异常者,应积极找病因,注意代谢病检查,并长期随访。     

婴儿先天性胆道闭锁的麻醉方法探讨

目的:探讨婴儿胆道闭锁的麻醉方法.方法:将23例胆道闭锁患儿随机分成两组:A组(n=12)单纯全麻组,B组(n=11)全麻复合硬膜外组,记录术前(T1)、手术切皮(T2)、胆道探查(T3)、拔除气管导管(T4)时病人的MAP和HR的变化,记录各组芬太尼、阿曲库铵、异氟烷的用量和停异氟烷吸入后病人呼吸恢复的时间、拔管时间.结果:两组MAP和HR在术前无显著差别(P＞0.05),在T2、T3及T4时A组高于B组(P＜0.05);呼吸恢复的时间、拔管时间A组高于B组(P＜0.05);全麻药的用量A组高于B组(P＜0.05).结论:两种方法均可用于婴儿胆道闭锁手术,但B组更优于A组.     

~(131)碘玫瑰红肝胆连续扫描对婴儿黄疸的诊断

本文应用~(131)碘-玫瑰红对19例黄疸婴儿作了检查。结果显示:13例胆道闭锁患儿在注射~(131)碘-玫瑰红后24小时仍无肠影出现;5例新生儿肝炎肠道显影;另1例胆道狭窄肠道显影延迟(假阴性)。用本法连续扫描检查方法简便、安全、准确性较高。诊断的关键在于熟悉各种类型黄疸图像的特点以及细致的分析。     

细针经皮肝穿刺胆道造影术在婴儿胆道闭锁诊断中的应用

本文主要介绍细针经皮肝穿刺胆道造影术在婴儿胆道闭锁诊断中的应用。1983—1990年共收集了19例,其中男14例,女5例。操作方法与成人不同点为:①婴儿须在全麻下进行;②婴儿进针穿刺的部位较成人偏低;③穿刺针在肝内寻找胆管的速度宜慢,找到胆管后注射造影剂的速度要怏。此造影术不但能鉴别婴儿的阻塞或非阻塞性黄疸,还能确定胆道闭锁的部位和类型,为外科手术提供确切的依据。     

Association of miRNA-492 rs2289030 G>C and miRNA-938 rs2505901 T>C Gene Polymorphisms with Biliary Atresia Susceptibility

Biliary atresia (BA) is one of the most common and enigmatic forms of neonatal cholestasis and is characterized by inflammation and obstruction of extrahepatic bile ducts resulting in biliary cirrhosis, which occurs in 1 in 8,000 to 1 in 18,000 live births[1]. Revealing of the mechanisms underlying BA is crucial for early diagnosis, intervention, and better prognosis. The etiology of BA remains unclear, and currently, noncoding and epigenetic factors, rather than classic genetic alterations, are assumed to be responsible for genetic predisposition to BA.     

5769例新生儿心脏彩超筛查结果分析

目的 了解新生儿先天性心脏病的患病情况,为制定和采取干预措施提供依据.方法 对2015年10月-2016年9月分娩的5 769名新生儿进行心脏彩超检查,根据筛查结果进行统计分析.结果 共筛查出182例新生儿先天性心脏病,患病率3.15%,先天性心脏病新生儿中女婴比例较高,差异边缘显著,早产儿比例较高,差异有统计学意义,产母年龄和正常组分布相近.先天性心脏病类型中室间隔缺损和房间隔缺损的构成比分别排第一位(48.90%)和第二位(38.46%),严重先天性心脏病仅占5.43%.结论 新生儿先心病的发病率较高,采用心脏彩超筛查可尽早发现先心病患儿,同时需做好先心病患儿的随访工作,及时进行干预.     

新生儿消化道常见畸形治疗进展

新生儿先天性畸形是婴儿死亡的重要原因之一。新生儿消化道畸形的发生率在新生儿先天性畸型中居第三位,常需进行手术治疗。该文介绍了食道闭锁、先天性幽门肥厚狭窄、小肠闭锁、先天性巨结肠及胆道闭锁等畸形手术治疗的进展。     

EFFECT OF INFANT FORMULA SUPPLEMENTED WITH OLIGOSACCHARIDES ON STOOL CHARACTERISTICS OF INFANTS

It is common for many formula-fed infants to beswitched from one formula to another either by theirparents or by the physicians. The reasons for suchfrequently formula switching are sometimes elusive.Most of the changes occur because of perceived ab-norma…     

应用组织芯片技术筛查胆道闭锁的病毒感染研究

目的应用组织芯片技术研究病毒感染与小儿胆道闭锁的关系。方法利用组织芯片技术检测42例胆道闭锁和5例对照组患者肝脏组织中的巨细胞病毒（CMV）和EB病毒（EBV）感染情况。结果在42例胆道闭锁患者肝脏组织中,其中CMV阳性26例（61．9％）,EBV阳性3例（7．14％）,对照组5例中均未检测到以上病毒的存在。结论胆道闭锁与病毒感染之间存在相关性,其中以CMV感染关系最为密切,可能作为其发病机制中的一个促发因素,最终引起胆道闭锁;抗病毒治疗可能会改善CMV感染EHBA预后。     

Results of surgical treatment for extrahepatic biliary atresia in United Kingdom 1980-2. Survey conducted on behalf of the British Paediatric Association Gastroenterology Group and the British Association of Paediatric Surgeons

A postal survey identified 114 infants with biliary atresia (roughly one in 21 000 live births). Biliary operations were performed on 107. Of the 105 infants who were followed up, 35 were free of jaundice at 10 months to 3 1/2 years. Good results occurred most often in those operated on by 12 weeks and were also related to the number of cases operated on in each centre. Only two of 18 infants treated in centres dealing with one case a year were free of jaundice compared with 11 of 38 at centres treating two to five cases a year and 22 of 49 in a centre treating more than five cases a year. Jaundice in an infant of more than 2 weeks associated with yellow urine or pale stools is never physiological and requires urgent investigation to identify causes for which effective treatment may be possible. Identification of suspected cases by 4 weeks of age and a greater concentration of investigative and surgical skills should improve the short term results of surgery and the long term prognosis of biliary atresia.