Biliary Atresia and Related Disorders of the Biliary Tract

8/19/2019 Biliary Atresia and Related Disorders of the Biliary Tract

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Biliary atresia and related disorders of the biliary tract, such ascholedochal cysts,must be considered in the dierential diagnosisof prolonged conjugated hyperbilirubinemia in the newborn(neonatal cholestasis). In this chapter,we review the current statusof diagnosis and management of these disorders, as well asadvances in the intriguing quest for an understanding of their

pathogenesis.OVERVIEWeonatal hepatobiliary diseases, including biliary atresia, choledochalcysts, and !idiopathic" neonatal hepatitis, have historicallybeen viewed as a continuum # a gradation of manifestationsof a basic underlying disease process in which giantcell transformation of hepatocytes is strongly associated within$ammation at any level of the hepatobiliary tract. %hese diseaseentities may be polar end points of a common initial insult,as originally stated in the unifying hypothesis of &anding '. %he end result represents the sequela of the in$ammatory processat the primary site of injury. &anding suggested that thisin$ammatory process may injure bile duct epithelial cells, leading

to either duct obliteration (biliary atresia) or wea*eningof the bile duct wall with subsequent dilatation (choledochalcyst ). %he lesions may be dependent on the stage of fetal developmentwhen the injury occurs and the site within the developinghepatobiliary tree at which the injury occurs ',+. relationship of the pathogenesis of these obstructive cholangiopathiesof infancy to the process of development is suggestedby the association with disorders of situs determinationsuch as the polysplenia syndrome and the observation of the so-called ductal plate malformation within the liver of afew patients with biliary atresia. %he ductal plate malformationis postulated to represent either a primary developmentalanomaly or disruption of a developmental sequence early infetal life, resulting in incomplete regression of the immaturebile ducts '+. In contrast, most patients with biliary atresiahave the late-onset type, which probably occurs after maturationof the intra- and etrahepatic bile ducts/ this representsinjury (destruction) of fully formedstructures '+.%hedynamicnature of the underlying process has been further suggestedby an apparent postnatal evolution of patent to atretic ducts0patients initially shown to have neonatal hepatitis with a patentbiliary systemsubsequently were found to have acquired biliaryatresia. %he overlap concept is additionally supportedby the frequentdocumentation of intrahepatic ductal injury in patientswith extrahepatic biliary atresia '1,2. 3epletion of intrahepatic

bile ducts is observed regularly at autopsy in children with biliaryatresia who were never subjected to a biliary drainage procedure'4.In biliary atresia, the initial insult and the sustaining mechanismsremain unde5ned. 6or eample, although viral infectionis a postulated initial insult, no speci5c viral agent has beenreproducibly detected in tissue from aected infants, nor isthere conclusive serologic evidence of their presence '7. 8thertheories (discussed below) include defective embryogenesis oran altered immune response to injury. 6urther studies are warranted/biliary atresia and related disorders continue to oerclinicians and scientists stimulating challenges.BILIARY ATRESIA

Biliary atresia is the end result of a destructive, idiopathic,in$ammatory process that aects intra- and etrahepatic bileducts, leading to 5brosis and obliteration of the biliary tract


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and eventual development of biliary cirrhosis '7. %his disordershould be of interest to all individuals involved in basic andclinical studies of diseases of the liver/ the rapidly progressive5bro-obliterative process may represent a paradigm for otherforms of hepatobiliary injury, perhaps re$ecting an interrelationshipbetween genetic predisposition and environmental

eposure '7.Biliary atresia is the most common cause of chroniccholestasis in infants and children, and because of the high frequencyof progression to end-stage liver disease, it is the mostfrequent indication for liver transplantation in the pediatric agegroup. %here is general agreement that the older theory that

biliary atresia was caused by failure of recanali9ation of embryonicbile ducts should be abandoned. %he lesion, in mostpatients, is not a true congenital malformation but seems tobe acquired in late gestation or after birth '7#:. ;ecent studiesof liver samples obtained from patients with biliary atresiaat the time of diagnosis revealed unique proin$ammatory features

',+#2. %here is a slight female predominancein most series. 8ne population-based birth defectssurveillance systemfor infantswith biliary atresia in metropolitantlanta calculated an incidence rate of =.>1 per =,=== livebirths '4. %here was signi5cant seasonal clustering of thedisease, with rates three times higher in infants born between3ecember and ?arch. ;ates were signi5cantly higher amongnonwhite infants. %he demonstration of signi5cant seasonalclustering in this and other studies supports the theory thatbiliary atresia may be caused by environmental eposure (consistentwith a viral cause) during the perinatal period '7.Clinical Forms@chwei9er '7 has postulated the eistence of at least two dierentforms of biliary atresia, with disparate pathogenesis0 a fetalor embryonic form, and a peri- or postnatal form. In patientswith the less common fetal form (=#14A of all patients),

cholestasis is present from birth, with no jaundice-free interval.Bile duct remnants may not be detectable in the hepatic hilum,and there is a high frequency (=#+=A) of associated malformationssuch as the !polysplenia syndrome," which may includecardiovascular defects, asplenia or abdominal situs inversus,intestinal malrotation, and positional anomalies of the portalvein and hepatic artery '> (%able +.). %he fetal form of biliary atresia may represent a true malformation syndrome(defective embryogenesis). In contrast, the postnatal form, inwhich there are no associated congenital abnormalities, maybe the result of an acquired obliteration. %hese two forms havenot been distinguished on the basis of histology of porta hepatisspecimens/ both forms may have in$amed and obliterated bile

duct segments in this resected tissue mass.In the series of 3avenport et al. '> of 1=: patientswith biliary


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atresia, +1 (>.4A) had polysplenia, + had double spleens,and + had asplenia. ll +> had anomalies that may occur inthe polysplenia syndrome/ the investigators used the term biliary atresia splenic malformation syndrome to describe all suchinfants '>. In this series, infants with this syndrome had a

lower birth weight and a higher incidence of maternal diabetescomparedwith nonsyndromic cases. %he etrahepatic anatomyof the biliary tract also reportedly was dierent, includinginstances of what they termed biliary agenesis. %hese 5ndingssuggest that either the timing or the nature of the lesion of this!fetal" subgroup may dier from that of the more usual !postnatal"case.e believe that the postnatal formof biliary atresiamay be the result of the sporadic occurrence of a virus-inducedor virus-initiated progressive obliteration of the bile ducts,withsome degree of intrahepatic bile duct injury '7,>,:. Biliaryatresia in both subtypes appears to involve an ongoing in$ammatoryprocess that produces complete or partial sclerosis of etrahepatic bile ducts and progression to cirrhosis '>,


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may be seen as late manifestations if biliary cirrhosis hassupervened. t present, an increased awareness to ensure earlydiagnosis and development of methods to prevent progressivehepatic 5brosis are needed. Early recognition of babies whohave biliary atresia is especially critical for optimal intervention/ideally, biliary atresia should be identi5ed by the time of

the 5rst well-baby visit after discharge from the hospital. %heimportance of a prompt and precise diagnosismust be stressedto all pediatric health care providers. In the Fnited Dingdom,an educational eort (the Gellow lert campaign) was establishedto indicate the signi5cance of jaundice persisting after2 days of age. Copulation screening also has been considered'+=,+. %he ultimate goals are to de5ne the pathogenesis of biliary atresia and establish preventive strategies.

Cause and Pathogenesis o Biliar! Atresialthough our understanding of the cause and pathogenesis of

biliary atresia has remained unchanged for several decades,there is now increasing interest with resultant studies investigatingmechanisms of this disease. %heoretic considerationsof the cause of biliary atresia have been based on epidemiologicand clinical features.%wo critical clinical features oer potentialclues about chief biologic processes. %he 5rst is the onset of diseaserestricted to the perinatal or immediate postnatal period(H2 months). %he second is in$ammation and 5brosis of theetrahepatic bile ducts. In the !typical" patient, the structuralchanges present in the hepatobiliary tract suggest a progressionof the lesion from acute cholangitis to 5brotic obliteration of the ducts (6igure +.). %he dynamic nature of the obliterativeprocess is illustrated by the fact that atresia has been found atautopsy or reeploration in infants previously shown to havepatent etrahepatic ducts or !neonatal hepatitis" '7,+,1.

?ultiple studies have focused on normal and altered bileduct morphogenesis and the role of various factors (infectiousor toic agents and metabolic insults) in isolation or in combinationwith a genetic or immunologic susceptibility to biliaryatresia '7. Biliary atresia is not thought to be inherited in themajority of patients. %he absence of documented recurrence insiblings of infants with biliary atresia and reports of di9ygotic

and mono9ygotic twins discordant for biliary atresia appears toeclude simple?endelian genetic causes '++#+2. %he conceptthat an acquired obliterative process underlies biliary atresia isattractive and suggests that a virus-related in$ammation mayinitiate the sequence that leads to 5brosis and luminal obstruction',#12. %he demonstration of signi5cantseasonal clustering provides support for the theory thatbiliary atresia may be caused by environmental eposure (consistent

with a viral cause) during the perinatal period '4.?ultiple potential etiopathogenic viruses have been ruled out


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as !suspects." epatitis , B, and J virus infections are notrelated to biliary atresia '7, and there was no apparent increasein the incidence of biliary atresia during rubella epidemics.Jytomegalovirus (J?K), which characteristically infects thebiliary epithelium, has been suggested as a cause of biliary atresia'12#1>. 6or eample, a @wedish study showed a higher

prevalence ofJ?Kantibodies in mothers of infantswith biliaryatresia, andJ?K3was present in livers from< of : infantswith biliary atresia '1>. n important role for J?K in thepathogenesis of biliary atresia, however, seems unli*ely becauseeamination of porta hepatis specimens by in situ hybridi9ationand polymerase chain reaction (CJ;) using J?K 3 probeswas negative '17. 3rut et al. '1: reported a high prevalence of human papillomavirus 3 in archived liver tissue of 7 of :rgentinean children with biliary atresia compared with noneof 1= controls or age-matched autopsy specimens from patientswithout liver disease. uman papillomavirus 3 also wasdetected in cervical swabs from mothers of four patients withbiliary atresia, and the types of papillomavirus were concordant

between infants and mothers. %here is no animal model,however, demonstrating the consequences of human papillomavirusinfection in an immature liver, nor have these 5ndingsbeen con5rmed elsewhere.?ason et al. '1 and for locali9ationof reovirus particles in the porta hepatis of one infant'+:. It had been *nown for some time that this virus couldcause an obliterative cholangiopathy in weanling mice/ a similarityeists between the hepatitis with biliary tract in$ammationinduced by reovirus type 1 infection in thisweanling mousemodel and the progressive postnatal 5brotic obliteration of theetrahepatic bile ducts and liver cell injury noted in biliaryatresia '+>#+,+:. %his


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case remains unique, however, because reovirus antigen couldnot be detected in any specimens of etrahepatic biliary tissueremoved at the time of portoenterostomy in another series of eight patients with biliary atresia '21. %wo studies have eaminedhepatobiliary tissues from infants with biliary atresia forevidence of reovirus infection. @teele et al. '22 failed to detect

reovirus ; in preserved tissues using nested reverse transcriptionCJ;. %yler et al. '2, however, subsequently reported5nding CJ; evidence of reovirus infection in fresh fro9en liveror bile duct tissue from of += patientswith the perinatal formof biliary atresia, in = of 1 patients with the fetal form, and inonly :#4A of autopsy control or other liver disease controlsubjects younger than year. %he discrepancies between thesetwo studies may lie in the methods of preparation of the tissue(fro9en vs. archived 5ed tissue), dierentmethods of; isolation,and the use of probes for dierent genes. recent studyof reovirus type 1 infection in the immediate postnatal perioddid not show etrahepatic obstruction '24.;iepenho-%alty et al. '1= have reported the development

of etrahepatic biliary obstruction in newborn mice orallyinoculated with group rotavirus. %hese investigators alsohave presented evidence for CJ; ampli5cation of group Jrotavirus sequences from livers of patients with biliary atresia,for immunoreactivity to group J rotavirus in serum of patients with biliary atresia, and for group J rotavirus particlesin the stool of patients with biliary atresia '1. dditionalstudies in newborn mice have clearly shown the lesion to residein the biliary epithelium/ the obstructive phenotype is presentonly when rotavirus infection occurs in the 5rst few days of life'27#2:. In one study, prophylactic treatment with interferon

prevented biliary atresia induced by rotavirus in susceptiblenewborn mice, which also supports a viral etiology '1+. %hismodel of rotavirus-induced biliary injury may oer a uniqueopportunity to study the mechanisms of biliary atresia becauseit recapitulates two consistent clinical features of the disease inhumans0 the onset of disease in the immediate neonatal periodand the progressive cholangiopathy.dditional studies are needed to further investigate a relationshipbetween reovirus, rotavirus, or any other virus in thepathogenesis of biliary atresia '11,12. Investigation into thecontribution of virus-initiated immune or autoimmune mechanismsof hepatobiliary injury in these disorders may yieldinformation essential for development of treatment or prevention

strategies. It is unli*ely, however, that antiviral therapyalone would alter the natural history of biliary atresia if thepathologic process is an immunologic reaction to a precedingviral injury, without ongoing viral replication '7,2.Defect in Morphogenesis %he hypothesis that a defect inmorphogenesis of the biliarytract is a mechanism for the pathogenesis of biliary atresia isappealing '7, especially considering the coeistence of otheranomalies, particularly anomalies of visceral organ symmetry(%able +.), that occur in=#1=Aof infantswith biliary atresia. %an et al. '2


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fertili9ation, resulting in the formation of large tubular bileducts surrounded by thic* mesenchyme. &uminal continuitywith the etrahepatic biliary tree was maintained throughoutgestation. Jontrary to previous speculation, no !solid phase"was documented during the development of the etrahepaticbile duct. Eamination of the biliary remnants in biliary atresia

showed that the porta hepatis was encased in 5brous tissue,with a variable pattern of obliteration of the common hepaticand common bile ducts. %here were similarities on anticyto*eratinimmunostainingbetween the abnormal ductuleswithinthe porta hepatis in biliary atresia and the normal developingbile ducts during the 5rst trimester. %he investigators proposedthat biliary atresia may be caused by failure of the remodelingprocess at the hepatic hilum, with persistence of fetal bile ductspoorly supported by mesenchyme'2


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role in mediating dierentiation of mesenchymal tissue intoepithelial cells, scattering and remodeling these epithelial cellsin a manner that results in formation of a lumen '7,42. owever,no biliary abnormality was reported in mice with targetedinactivation of the receptor '44,47. In contrast, abnormalitiesin the biliary tract have been reported in mice with genetic

mutations in Hes1, Hnf6, Hnf1b, and Foxm1b, and raise questionsabout the potential role of these genes as susceptibilityfactors or modi5ers of disease in humans '4>#7.Disordered Immunologic Mechanismsn abnormality in the immune or in$ammatory responsein patients with biliary atresia has been proposed. Biliary atresiamay be the result of a !multiple hit" phenomenon '7+. %he theory holds that a viral or toic insult to the biliaryepithelium leads to newly epressed antigens on the surface of bile duct epithelia, which in the proper genetically determinedimmunologic milieu (e.g., major histocompatibility molecules)are recogni9ed by circulating % lymphocytes that elicit a cellularimmune injury, resulting in in$ammation and 5brosis of

the bile duct '7+. In support of this notion, @ilveira et al. '71reported an association of the humanleu*ocyte antigen (&)-B+ allele and haplotypes


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controlling the in$ammatory obstruction of the neonataletrahepatic bile duct in the mouse model of rotavirus-inducedeperimental biliary atresia '>4. Fsing this model, the loss of interferon gamma completely prevented duct obstruction andincreased long-term survival. 6uture studies are necessary todetermine whether inactivation of interferon gamma may constitute

a therapeutic tool to halt disease progression in childrenwith biliary atresia.Environmental Toxic Exposure3espite the apparent eistence of time#space clustering of cases of biliary atresia, there is no conclusive evidence of a lin*between maternal drug ingestion or environmental eposureand the subsequent development of biliary atresia in the newborn.Vascular Abnormalities3evelopmental abnormalities in the position of the portalvein and in hepatic artery anatomy at the porta hepatis arecommonin patientswith biliary atresia. %here are no consistenteperimental data, however, to con5rm the hypothesis that a

vascular basis, suchas ischemia, is a cause of the progressive ductinjury seen in biliary atresia '>7. In utero devasculari9ation orligationof the etrahepatic bile duct has been attempted insomeanimal models, and lesions similar to the less common !correctable"variants of biliary atresia have been produced '>>/however, other studies have been inconclusive '>:.#iagnosis o Biliar! AtresiaKarious laboratory tests, imaging methods, and biopsy sampleshave been utili9ed in attempts to establish the diagnosis of biliaryatresia, particularly in dierentiating it from various formsof intrahepatic cholestasis (idiopathic neonatal hepatitis) '7.In our eperience, the most reliable information is obtainedby review of hepatic histopathology followed by direct visuali9ationof obliterated etrahepatic bile ducts (intraoperativecholangiography). Cercutaneous liver biopsy has a diagnosticaccuracy of


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approach0 () Crompt recognition of cholestasis is essential. Laundice in an infant must not be attributed erroneously

to physiologic hyperbilirubinemia or to breast-feeding/ fractionationof the serum bilirubin usually separates out theseconditions, which cause a predominant elevation (O:=A) of unconjugated bilirubin levels. In addition, the serum bile acidconcentration in blood obtained during the 5rst = days of life is elevated signi5cantly in infants with cholestasis '+=/ thismay oer a potential screening method. (+) Crocedures shouldbe epeditiously performed to rule out potentially devastatingillnesses such as sepsis, endocrine disorders, and nutritionalhepatotoicity attributable to metabolic disease (e.g., galactosemia).3e5nitive detection is usually straightforward, andinstitution of appropriate treatment may prevent further liver

injury. Early recognition of speci5c, treatable primary causes of neonatal cholestasis then is attempted. Early in the evaluationof any infant with cholestasis, other clinical issues need to beaddressed.ypoprothrombinemiamay be present regardless of the cause of cholestasis/ administration of vitamin D may preventspontaneous, life-threatening bleeding, such as intracranialhemorrhage. (1) !Idiopathic" neonatal hepatitis must bedierentiated from biliary atresia because the prognosis andmanagement dier signi5cantly. In infants with biliary atresia,progressive 5brosis rapidly occurs/ therefore, signi5cant delayin diagnosis or treatment must be avoided.o single test is entirely satisfactory in discriminatingneonatal hepatitis (intrahepatic cholestasis) frombiliary atresia/

however, historical and clinical features may aid in the dierentialdiagnosis. eonatal hepatitis is reported to have a familialincidence of 4#+=A/ the intrafamilial recurrence ris* is negligible


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for biliary atresia ':,>,:,:1. %echniques thatare used etensively in evaluation of adults with cholestatic disease,such as percutaneous transhepatic and endoscopic retrogradecholangiography, are not of proven value in children ':4. %he role of magnetic resonance cholangiography is unde5ned':7#::. Fltrasonography may detect dilation of the biliarytract, the presence of a choledochal cyst, or, in patients with biliaryatresia, absence of the gallbladder.Jhoi et al. ':


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Role of Liver Biops In our eperience, clinical eamination, careful andrepeated eamination of the stool, and needle biopsy of the livercorrectly identify a large majority of patients with biliary atresia.In most patients, biopsy can be performed safely using the?enghini technique ofpercutaneous aspirationwith local anesthesia

'>,:,


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%he approach outlined here is not without pitfalls/ cautionshould be eercised in interpretation of certain studies,especially in very young infants. In four patients reported by?ar*owit9 et al. ', scintigraphic evidence of biliary atresiawas present, and intraoperative cholangiography failed to

demonstrate any proimal intrahepatic biliary radicals/ therefore,hepatoportoenterostomy was performed. %here was inadequatepostoperative drainagewith cholangitis, development of cirrhosis in two, and death from hepatic failure in one infant.@ubsequently, a histologic and clinical diagnosis of intrahepaticcholestasis (lagille syndrome) was made in each of thefour patients. %he progression of the hepatic disease in thesepatients demonstrated that portoenterostomy had severely andadversely altered the course of their disease. 3uring cholangiography,an absence of retrograde $ow into the proimal intrahepaticducts does not eclude the presence of a patent, albeit

hypoplastic, etrahepatic biliary duct system in a patient withintrahepatic disease. %he liver disease in intrahepatic cholestasissyndromes (e.g., lagille syndrome) is not amenable to surgicalcorrection, and portal dissection should not be attempted.$anagement o Biliar! Atresiat present, there is no speci5c medical therapy for biliary atresia. %he 5rst brea*through in the surgical therapy of patientswith biliary atresia occurred in the late


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!urgical Management @equential surgical therapy for biliary atresia is divided intotwo steps0 the establishment of a secure diagnosis, then theconstruction of the portoenterostomy '. %he importanceof establishing an unequivocal diagnosis before proceeding toCE cannot be overstated. %he initial step in the eploration

should both con5rmthe diagnosis of biliary atresia and ecludeother diagnoses not improved by operative intervention, suchas various forms of intrahepatic cholestasis. %his can be donethrough direct observation and de5nition of the distal biliaryductal anatomy using direct cholecystocholangiography. %he liver in patients with biliary atresia is 5rm and shows acholestatic brown-green discoloration often accompanied bymultiple subcapsular telangiectasias. %he gallbladder remnantis usually 5brotic but may contain a small amount of clearmucoid secretions. Early in the course of the disease, the hilarstructures and the biliary ductal remnant may show a considerableamount of edema. In older children, these structures are5brotic and more diRcult or impossible to identify. If these

5ndings are accompanied by a 5brotic gallbladder, cholangiographyis not necessary and biliary atresia is con5rmed. If the gallbladderis not obliterated, gentle cholecystocholangiography isunderta*en to further de5ne the operative course. Because of the small gallbladder volume and minimal ductal si9e in infants,the cholangiogram should be visuali9ed from its onset using$uoroscopy to avoid overdistention and etravasation, whichpreclude successful visuali9ation of ductal structures. If the ductalsystem is normal or the bile ducts are small but patent, agenerous wedge and needle biopsy is obtained/ however, biliaryreconstruction should be speci5cally avoided. If $ow intothe distal biliary tract is seen but no proimal $ow is documented,a light spring-loaded vascular occlusion clamp shouldbe placed on the supraduodenal biliary structures before additionalattempts to visuali9e the proimal ductal system. %heDasai CE should be underta*en if no proimal patency is documented. Anatomic Variants of Biliar Atresia %he anatomy of the abnormal etrahepatic bile ducts inpatients with biliary atresia is variable. %he currently acceptedclassi5cation of anatomic variants of biliary atresia is based onthat proposed by the Lapanese @ociety of Cediatric @urgeons,which divides cases into three principal types '==0 type 1,atresia of the common bile duct/ type 2, atresia of the commonhepatic duct/ and type &, atresia of the right and left hepaticducts. 6urther subdivisions include the variable morphology of

the gallbladder and the distal common bile duct '==. bsenceof the proimal biliary tree has been termed biliary agenesis'=1. !Jorrectable" lesions # having distal common bile ductatresia but a patent portion of the etrahepatic duct up to theporta hepatis and joining the intrahepatic ducts # allow directdrainage into a ;ou-en-G anastomosis '


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ecision of the obliterated etrahepatic ducts and apposition of the resected surface of the transected porta hepatis to the bowelmucosa in the ;ou-en-G loop (CE) # the Dasai procedure'#1,


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after CE '+4#+. Episodes of cholangitis may precedediscovery of the cysts.Role of Reoperation #ollo$ing "epatoportoenterostom @everal series have emphasi9ed the potential value of reoperationin patients with cessation of bile $ow after initial successor in patients with refractory cholangitis. In many patients,debridement or revision of the scarred area was associated withthe reestablishment of bile $ow '+,1,


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consequence of repetitive but misdirected attempts to reoperateon poorly selected candidates with a poor prognosis forimprovement or recurrent episodes of bacterial peritonitis.OutcomeCrogressive biliary cirrhosis and hepatic failure may occurdespite apparent success in achieving bile drainage '7. 6actors

that contribute to failure include stenosis of the anastomosis,ascending cholangitis, and progressive loss of intrahepatic bileducts thatmayhave been injured before the drainage procedure.&iver transplantation is necessary in infants with a failed CE,manifest by progressive hepatocellular decompensation, jaundice,refractory growth failure with hepatic synthetic dysfunctionand the development of a coagulopathy, or intractable portalhypertension with recurrent gastrointestinal hemorrhage orhypersplenism '1,1


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hypertension. recently reported series of children who developedCC% demonstrated that clinical symptoms are subtleand thus may be overloo*ed '27. Jhildren with portal hypertensionwho develop a new heartmurmur, dyspnea, or syncopeor who are being evaluated for liver transplantation requireevaluation for CC% '27. Electrocardiography and chest

radiography are insensitive screening tests for CC%, hencean echocardiogram and cardiology evaluation may be neededto con5rm the diagnosis '27.lthough the success rate for biliary enteric anastomosis inpatients with biliary atresia cannot be predicted, it remains themost reasonable initial approach '7,1. retrospective studywascarried out tode5nethe long-termoutcomeof childrenwhohave undergone surgery for biliary atresia '+. 8f ++ children,1:A were alive after = years/ however, 5rm hepato- andsplenomegaly were present in about >4A. ormal liver functiontests and an absence of portal hypertension were observedin only ,2:. &iver transplantationshould be delayed as long as possible to permitmaimal growth. ;epeated attempts at revision of the CE orportosystemic shunting, however,may be ineective and rendereventual transplantation more diRcult.Cediatric patients undergoing liver replacement today canepect survival rates approaching ,2:,4=. %his creates an !epidemiologic disparity" because most pediatricdonors are of school age or older. Jonsequently theremay be an increased death rate in pediatric patients awaitingliver transplantation/ alternatively, suboptimal donor organsmay be accepted in a desperate attempt to address recipient

needs '4=. %he use of reduced-si9e liver transplantation as aninitial strategy was successful in both improving patient survival


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and decreasing the waiting-list mortality rate '4=,4.@ince the institution of segmental transplantation at JincinnatiJhildrenSs ospital ?edical Jenter, the number of deathswhile awaiting donor organ availability and the incidence of hepaticartery thrombosis have been reduced dramatically. Beforethe introduction of reduced-si9e liver transplantation at our

center, +. ;educed-si9e liver transplantationis not the ideal solution/ however, epansion of thedonor pool may be possible through etension of the surgicaltechniques used to prepare reduced-si9e allografts. %he needfor orthotopic liver transplantation in small pediatric patientsstimulated the development of other innovative operative proceduresbased on the concept of reduced-si9e allografts/ theseinclude split liver transplantation and the use of living, relatedorgan donors. &iver transplantation survival rates for livingdonor, split, and reduced-si9e transplantation are similar tothose with whole-organ graft transplantation in children olderthan + years '2>,2:,4=. ;ecent data have suggested thatliving donor transplantation is best performed in recipients#+ years of age.3espite the high overall success rate of liver transplantationin children, multiple challenges remain, including improvementof methods of preoperative management to addressthe problems of malnutrition, improvement of methods of immune suppression to prevent graft loss and avoid lymphoproliferativedisease and other infectious complications,and development of protocols to avoid growth suppression'1,2>,2:,4:. Jhildren are particularly sensitive to the consequencesof both under-immunosuppression (rejection) and

over-immunosuppression (posttransplantation lymphoproliferativedisease, renal insuRciency, infection). %he latter is complicatedby the fact that children appear to be more immunoresponsivethan adults. careful balance is sought throughoutthe posttransplantation period.e also must strive to provideservices in a cost-eective manner.Liver Transplantation as %rimar Therap for Biliar Atresia %hose who propose primary transplantation as the procedureof choice for children with biliary atresia cite severalpotential advantages, including the lac* of adhesions in a previouslyundisturbed abdomen leading to a decreased need forblood products '4


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even in these critical infants '7=. owever, the most compellingargument against primary transplantation centers oninadequate donor resources. ?ortality awaiting transplantationis highest in the over--year-old group, and an in$u of biliary atresia infants would further increase the disparity andmortality. @election of candidates for primary transplantation

is not well accepted, ecept possibly in patients in whom liverdisease is so advanced (advanced age and cirrhosis) that bile$ow cannot be restored. Jonservative decision ma*ing shouldbe practiced in this regard, *nowing that even partial return of bile $owmay delay transplantation to an age at which prognosisis more favorable and a donor organ more readily available. %he limitations and potential pitfalls of primary liver transplantationhave led to adaptation of a se(ential approach inthe management of biliary atresia (6igure +.4). CE wouldobviate the need for transplantation for patients in whom theprocedure was a long-termsuccess and delay transplantation inanother signi5cant proportion.%he cost bene5ts of this strategyhave been discussed '2. In our opinion, therefore, sequential

surgical therapy for biliary atresia should beginwith creation of

an CE. Infants with poor response will undergo transplantationwithin the 5rst + years. Jhildren with initially !successful"drainage but with progressive liver disease with portal hypertension,hypersplenism, variceal hemorrhage, and malnutritionwill need orthotopic liver transplantation at a later date. 8ccasionally,long-term survivors may not require transplantation.Jhardot et al. '7 reviewed all patientswith biliary atresialiving in 6rance and born between the years


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'7,2,4,2:,4=,72#7:. %hisincrease in survival results from technical operative improvementsand eperienced care management. major challengeis the high frequency of virus-related disease in children, especiallyJ?K- and Epstein#Barr virus#related. s the survivalrates following orthotopic liver transplantation in children haveincreased, health care providers have begun to measure theoverall health status of liver transplant recipients (functionaloutcome) as a complement to traditional measures of medicaloutcomes. %he overriding objective of hepatic transplantationin children is complete rehabilitation with improved qualityof life '2>,2:,7:. 6actors contributing to the attainment of this goal include improved nutritional status with appropriategrowth and development as well as enhanced motor andcognitive s*ills, allowing social reintegration.F'T'RE %he ultimate goal is to prevent biliary atresia/ to accomplishthat objective, a multicenter, multifaceted eort is necessary. %he ational Institutes of ealth have recently established aconsortium # %he Biliary tresia Jlinical ;esearchJonsortium(B;J) # consisting of ten pediatric clinical research centers inthe Fnited @tates '7


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Jholedochal cysts are considered to be congenital anomaliesof the biliary tract characteri9ed by varying degrees of cysticdilatation at various segments of the biliary tract (etrahepaticor intrahepatic). %he frequency of choledochal cysts is about in 4,=== live births in estern countries and as high as in=== live births in Lapan. %here is a mar*ed female predominance

(four to one) regardless of the racial origin. choledochalcyst (or congenital bile duct cyst) may be detected atany age and in any portion of the bile duct '>=#>1. %odani'>1 has proposed classi5cation of choledochal cysts into 5vesubtypes (6igure +.7, %able +.1). lthough cysts are uncommonlypresent in the neonatal period, this consideration mustbe included in the dierential diagnosis of neonatal cholestasis/antenatal diagnosis has been described '>2. Jysts are presentin up to+Aof infantswith obstructive jaundice. Infants presentin a manner simulating biliary atresia and, if unrecogni9ed,may have progressive disease. Crolonged obstruction results inbiliary cirrhosis, portal hypertension resulting from cirrhosis,and pressure on the portal vein by the distended cyst/ recurrent

pancreatitis is an unusual complication of the malformation'>1.

Biliary Atresia and Related Disorders of the Biliary Tract

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