atresia bilier 1.pdf

8/11/2019 atresia bilier 1.pdf

1/12

34 Global Journal of Gastroenterology & Hepatology,2013, 1, 34-45

E-ISSN:2308-6483/13 2013 Synergy Publishers

Biliary Atresia: A Challenging Diagnosis

Mostafa Mohamed Sira*, Tahany Abdel-Hameed Salem and Ahmad Mohamed Sira

Department of Pediatric Hepatology, National Liver Institute, Menofiya University, 32511 Shebin El-koom,Menofiya, Egypt

Abstract: Biliary atresia (BA) constitutes about one third of all neonatal cholestasis (NC) and the most commonindication (up to 50%) of liver transplantation (LTx) in children. Despite extensive studies, its etiopathogenesis has notbeen clearly revealed. Treatment is primarily surgical based on reinstitution of bile flow by Kasai portoenterostomy, thesuccess of which is largely dependent on the early diagnosis before 60 days of age. If portoenterostomy

is not successful

or not performed, LTx isthe only life-saving alternative. Accurate diagnosis of BA, particularly distinguishing it from other

causes of liver injury in the neonatal period, is challenging as there is a high degree of overlap in clinical, biochemical,imaging, and histological characteristics. There is no single preoperative investigation that enables the diagnosis of BAto be made with certainty. Liver biochemistry assessment, biliary radionuclide excretion scanning, magnetic resonancecholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), percutaneous needleliver biopsy, and laparoscopy can all be helpful, but their results are not individually diagnostic. The current reviewpresents an overview of BA with emphasis on the recent diagnostic modalities.

Keywords: Biliary atresia, diagnosis, Doppler, liver biopsy, neonatal cholestasis, ultrasound.

1. DEFINITION

Biliary atresia (BA) is an idiopathic progressive

inflammatory process of the extrahepatic bile ducts with

obliteration and concomitant ongoing damage of the

intrahepatic bile ducts resulting in chronic cholestasis,

progressive fibrosis, and eventually biliary cirrhosis [1].

2. EPIDEMIOLOGY

Although the incidence of BA is approximately 5 to

32 cases per 100,000 live births, it constitutes nearly

one third of all NC cases [2]. The reported incidence is

highest in Asia and the Pacific region [3]. The

estimates in Taiwan and Japan range from 1.1 to 3.7

cases per 10,000 live births [4, 5], while it occurs in

approximately 1 in 18,000 in Western Europe [3]. In the

United States, BA occurs with an estimated frequency

of 1 in 8000 to 15,000 live births, resulting in 250 to 400

new cases per year [6]. Females are affected slightly

more often than males [3]. Some studies of time- and

space-time distribution of BA have suggested seasonal

variation and clustering of cases [7].

3. CLASSIFICATION

Clinically, BA is classified into two types, perinatal

and embryonic. Perinatal, (acquired, or non-syndromic)

form of BA; accounts for approximately 90% of affected

infants. Patients with this type are asymptomatic,

anicteric at birth, and develop jaundice in the first

postnatal weeks. These infants are otherwise healthy

*Address correspondence to this author at the Department of PediatricHepatology, National Liver Institute, Menofiya University, 32511 ShebinEl-koom, Menofiya, Egypt; Tel: +2-048-222-2740; Fax: +2-048-223-4586;E-mail: [email protected]

and appear to suffer from a perinatal insult that leads to

biliary obstruction [8]. Embryonic (syndromic) form oBA; patients with this type have no jaundice-free

interval and suffer from one or more congenita

anomalies, such as interruption of the suprarena

segment of the inferior vena cava with azygous

continuation, preduodenal portal vein, midline

symmetric liver, intestinal malrotation, situs anomalies

bronchial anomalies, and polysplenia or asplenia. The

embryonic form thus appears to be caused by a

developmental abnormality of the biliary tree and

includes those infants with the biliary atresia splenic

malformation (BASM) syndrome [9].

Surgical (Anatomical) types of BA are classified on

anatomical basis, referring to the level and severity o

the obstruction. The most commonly used Japanese

classification describes 3 main types (Figure 1). Type I

atresia of the common bile ducts with paten

gallbladder (GB) and hepatic ducts (i.e. distal BA)

Type II, atresia of the common hepatic ducts with

patent right and the left hepatic ducts (i.e., proximal

BA). Type II is subgrouped into two subtypes. Type IIa

where the GB, cystic duct and common bile ducts are

patent (sometimes with a cyst in the hilum, i.e., cystic

BA). Type IIb; with the cystic, common bile duct and

common hepatic duct are all obliterated. Type III; is

characterized by atresia of the entire extrahepatic

biliary tree (i.e., complete BA) [10]. Most often, BA is

complete (type III, 73%) or subcomplete (type IIb

18%), with cystic BA and distal BA being infrequen

(types IIa and I, 6% and 3%, respectively) [11].

4. ETIOLOGY AND PATHOGENESIS

The basic etiology of BA is still not clear [1]. The

suspected causes generally fall into infection o


2/12

Biliary Atresia: A Challenging Diagnosis Global Journal of Gastroenterology & Hepatology, 2013 Vol. 1, No. 1 3

autoimmune-/immune-mediated categories, with the

possibility of inherited predispositions [12]. It was

proposed that BA was the result of a multihit

pathologic process, in which a viral or toxic insult to

biliary epithelium leads to newly expressed or altered

antigens on the surface of bile duct epithelia. These

antigens are presented by macrophages to T

lymphocytes. Cytotoxic T cells then elicit a T helper-1

cellular response causing bile duct epithelial injury,

eventually, resulting in fibrosis and occlusion of the

extrahepatic bile ducts [13].

4.1. The Infectious Causes

It was suggested that BA is caused by an immune

response to an unknown triggering event. As a

potential initiator of this immune process, a viral

infection has been considered. This hypothesis has

been supported by findings of individual viral strains in

BA patients [14]. It was also supported by the

observation that all livers of BA patients stained

positive for Mx protein (a myxovirus resistance protein)

and toll-like receptor, both of which are markers known

to be up-regulated during viral infections [15]. Differentviral agents have been associated with BA; such as

cytomegalovirus (CMV), human papilloma virus,

reovirus, and rotavirus [16, 17]. In contrast, no

association with hepatitis A, B and C viruses has been

found [18].

4.2. Genetic Causes

Several observations suggest that a genetic

component plays a role in the pathogenesis of BA as

familial cases have been reported [3]. It was reported

that about 20% of patients with BA have non-hepatic

congenital anomalies, including situs anomalies in 8%

The increased incidence of non-hepatic anomalies in

patients with BA and the genetic mutations reported in

subsets of patients with laterality defects suggest tha

multiple genes are involved [9]. Mutations in the

JAGGED1 gene; which are associated with Alagillesyndrome, have been found in about 10% of patients

with BA [12] suggesting that JAGGED1 could be a

modifying factor in patients with BA [13].

By analyzing the phenotype of hepatocyte nuclea

factor 6 (Hnf6)-knocked out mice, the GB was absent

the extrahepatic bile ducts were abnormal, and the

development of the intrahepatic bile ducts was

perturbed in the prenatal period [19]. Moreover

mutations in genes coding for alanine-glyoxylate

aminotransferase [20], X-prolyl aminopeptidase P and

adducin 3 genes [21] have also been linked to theoccurrence of BA.

4.3. Defective Morphogenesis

Several lines of evidence suggest that fetal form o

BA is caused by defective morphogenesis of the biliary

tree. Because anomalies of visceral organ symmetry

(polysplenia syndrome) are associated with BA, it is o

interest that a recessive insertional mutation in the

proximal region of mouse chromosome 4 or complete

deletion of the inversion (INV) gene in the mouse leads

to anomalous development of the hepatobiliary systemin this model [13].

4.4. Immunologic Causes

The immune response has received the mos

attention in human based studies of BA pathogenesis

[22]. Genes that encode a variety of immune regulatory

proteins, in part, control the susceptibility of immune o

autoimmune injury to biliary epithelia [23, 24].

The infiltration of CD4+ and CD8

+ T lymphocytes

and macrophages has been consistently observed inthe periductal space or along the duct epithelium in

conjunction with increased expression of cytokines

[25]. Davenport et al., [14] demonstrated that CD4+ T

lymphocytes and natural killer (CD56+) cells

predominated in the liver and extrahepatic bile duct o

patients with BA, and that intercellular adhesion

molecule-1 was expressed in sinusoidal endothelium

Ghonein et al., [26] demonstrated that hepatic

expression of intercellular adhesion molecule-1 was

Figure 1: Schematic illustration of biliary atresiaclassification. Illustration by Mostafa Sira, Department ofPediatric Hepatology, National Liver Institute, MenofiyaUniversity. GB: gallbladder; HD: hepatic duct; CHD: commonhepatic duct; CD: cystic duct; CBD: common bile duct.


3/12

36 Global Journal o f Gastroenterology & Hepatology, 2013 Vol. 1, No. 1 Sira et a

significantly higher in BA compared to other cholestatic

disorders in neonates. Moreover, Sira et al., [27]

reported that CD56 expressed on the majority of biliary

epithelial cells but not in other neonatal cholestatic

disorders.

4.5. Autoimmunity i n BA

BA shares features with several autoimmune

diseases, such as the female predominance, apparent

triggering by viral infection, and aberrant major

histocomptability expression in bile duct epithelium.

Consequently, it has been proposed that tissue injury in

patients with BA may represent an autoimmune-

mediated process. Some patients with BA were

positive for serum immunoglobulin G and antineutrophil

cytoplasmic antibodies, with higher levels of the

antineutrophil cytoplasmic antibodies compared with

children and adults with other liver diseases [13].

4.6. Vascular Etiology

An ischemic etiology for BA has been proposed

based on direct experimental evidence [28].

Intrahepatic and extrahepatic bile ducts receive their

blood supply exclusively from the hepatic arterial

circulation [13]. Several investigators have

demonstrated an arteriopathy in branches of the

hepatic artery of the extrahepatic biliary tree of patients

with BA. It has been proposed that the vasculopathy

may be the primary lesion in patients with BA [29].

4.7. Ductal Plate Malformation

Ductal plate malformation (DPM) is one of the

etiologic theories for the development of BA. It is a

possible primary factor in the pathogenesis of BA

causing defects in development of the intra hepatic bile

ducts, and this has been clinically observed in some

patients. This maldevelopment is thought to occur by

failure of the remodeling process of ductal plate

structures between 11 and 13 weeks of gestation [12].

Abnormal remodeling leads to DPM that is believed to

be responsible for the liver lesion of congenital hepaticfibrosis and other bile duct dysplasias. A number of

infants with BA show evidence of DPM on liver biopsy

[30].

4.8. Maternal Microchimerism

Maternal microchimerism occurs when a small

number of maternal cells are transferred to the

offspring during pregnancy. This is known to occur in

up to 40% of normal pregnancies. Maternal-fetal

lymphocytic transfer is known to occur during

pregnancy starting as early as the tenth week o

gestation and continuing up to delivery [31]

Significantly larger numbers of maternal XX+ cells

CD8+T cells, CD45

+cells, and cytokeratin-positive cells

were found in the portal area and sinusoids of patients

with BA in comparison with control patients suggesting

that maternal immunologic insults represent theunderlying pathogenesis in BA [32].

4.9. Toxin Exposure

Time and space clustering of cases of BA have led

to the proposal that an environmental toxin could be

involved in its pathogenesis. Currently, other than

infectious agents, no environmental agent has been

clearly associated with BA in humans. Two outbreaks

of BA in lambs and calves in Australia may have been

related to a fungal or other environmental toxin

exposure [13]. Other observations suggested thepresence of a phytotoxin or mycotoxin that could insul

the fetal hepatobiliary tree [33].

5. CLINICAL FEATURES

Infants with cholestasis may present with prolonged

conjugated hyper-bilirubinemia, passage of dark urine

with or without pale (acholic or clay-colored) stools

[34]. Intrahepatic and extrahepatic forms of cholestasis

share numerous clinical and biochemical features and

no clinical symptom is pathognomonic of each [35]

After birth, the clinical features of BA is jaundice(conjugated hyper-bilirubinemia lasting beyond two

weeks of life), acholic stools, dark urine and

hepatomegaly [3].

The general condition of the child is usually good

There is no failure to thrive, at least in the first months

Thereafter, weight loss and irritability develop

accompanied by increasing levels of jaundice. Late

signs include splenomegaly (suggesting porta

hypertension), ascites and hemorrhage (which can be

intracranial, gastrointestinal or from the umbilica

stump) due to impaired absorption of vitamin K. Iuntreated, this condition leads to cirrhosis and death

within the first years of life [3]. In our experience

intracranial hemorrhage may be the initial presentation

even before the appearance of jaundice.

6. EVALUATION OF BA

There are some obstacles that make an early

diagnosis of BA challenging. First, despite the need fo


4/12


early surgical intervention in this disease, there is a

general lack of understanding of the importance of

early identification among health care providers. Few

primary care physicians see more than 1 or 2 cases of

BA during their careers, whereas unconjugated

hyperbilirubinemia is extremely common, particularly

among breast-fed infants [36].A second obstacleis the

lack of convenient methods of screening. The efficacy

of stool color cards and conjugated bilirubin testing

were evaluated in Europe and Asia [4, 37-39]. A third

obstacleis that the jaundiced infant may not be seen at

the optimal time for identification of BA. The

unconjugated hyperbilirubinemia, due to breast feeding

in the first 2-3 weeks of life, may obscure the

conjugated hyperbilirubinemia of BA making it appear

that jaundice is actually improving. As the indirect

bilirubin falls during the first month of life in an infant

with BA who is also breast-fed, it may appear that there

is an overall improvement in jaundice [9].

6.1. Antenatal Diagnosi s

Antenatal diagnosis of BA remains exceptional. BA

types 1 and 2, which are rare, can be suspected on

antenatal ultrasonography (US) scans when a cystic

structure is detected in the liver hilum [40]. GB may be

visualised later in pregnancy, suggesting a delay in its

recanalisation process. When the GB remains

undetectable after birth, the possibility that the patient

has BA has to be carefully investigated [3].Features of

polysplenia syndrome may be detected by antenatal

US [41]

6.2. Clinical Diagnosis

The first step in diagnosis is the identification of

conjugated hyperbilirubinemia in an infant with

prolonged jaundice (beyond 2 weeks of age), pale

stools, or dark urine. An examination of the color of a

fresh stool specimen may be useful in differentiating

cholestasis (clay stools) from indirect

hyperbilirubinemia (bright yellow stools). The history

and physical examination may guide diagnostic studies

to identify specific causes of intrahepatic cholestasis[9]. Poddar et al., [42] reported that clay stool has a

high sensitivity (86%) but low specificity (76%) in

predicting BA. A similar finding was reported by El-

Guindi et al., with 92.5% sensitivity and 55.6%

specificity [43].

6.3. Laboratory Diagnos is

As time is an important factor in BA prognosis, a

wide-ranging approach of investigation is

recommended. Ruling out other etiological possibilities

in particular, congenital infection (TORCH

Toxoplasmosis, Rubella, CMV, Herpes simplex virus

serology is indicated [44].

High serum levels of GGT are commonly observed

in infants with BA. It is still unclear if normal values of

GGT may be found in patients with BA [45]. Alkalinephosphatase is produced by the epithelial cells of the

bile ducts and serum levels are increased in cases o

extra-hepatic obstruction, cholangitis and intrahepatic

cholestasis. Since alkaline phosphatase is also

produced in the bones, associated bone conditions

may cause difficulties in the interpretation of results. In

the case of high alkaline phosphatase levels and GGT

above 600 U/L, BA or another obstructive duct lesion

or even alpha-1 antitrypsin deficiency would be the

main diagnostic candidates. In cases of normal serum

values for alkaline phosphatase with GGT below 100

U/L, a diagnosis of progressive familial intrahepaticcholestasis, or of an innate error of bile acid synthesis

is possible. When the results for alkaline phosphatase

and GGT are not very high, it is probable that a primary

hepatocellular disease is present, such as idiopathic

neonatal hepatitis [46]. GGT has been reported as

discriminative tool of BA and at a cutoff value of 250.5

U/L it had a sensitivity of 86.7% and specificity of 65%

[26].

Serum bile acid levels are increased after birth and

remain high for the first month of life, thereafter slowly

declining to normal childhood levels by 1 year of age

Serum and urinary bile acids are increased further in

children with cholestatic liver disease. Furthermore, the

pattern of bile acid elevations in BA is not different from

that of other neonatal cholestatic liver diseases, excep

for progressive familial intrahepatic cholestasis [47]

The cholestasis of BA is not fully evident at birth bu

worsens thereafter. So, pathological elevations o

serum and urinary bile acids may not be present unti

2-4 weeks of age. Thus, bile acid levels cannot be used

alone for the screening and early detection of BA [48].

Progressive hepatic fibrosis, in spite of successfu

Kasai procedure, is a major problem in patients with

BA. Some serum markers have been used to assess

the stage of hepatic fibrosis before and after surgery

Serum hayaluronic acid and laminin were found to be a

significant markers of liver fibrosis in patients with BA

[49, 50]. Furthermore, serum procollagen III peptide

and type IV collagen were described to be significan

prognostic markers for the outcome of BA after the

corrective surgery. Lower levels of such markers were


5/12


associated with better outcome and good liver

functions [51].

6.4. Imaging

a. Plain X-Ray

While X-ray may reveal situs inversus or

dextrocardia associated with some cases of BA, it mayalso reveal different etiologies of cholestasis. Alagille

syndrome may be suspected if a vertebral image

showed butterfly wing. Congenital toxoplasmosis, or

CMV may cause cerebral calcifications. Periostitis and

osteochondritis were found to be highly indicative of

syphilis [44].

b. Ultrasonography

A rapid, non-invasive investigative method, and,

when performed by a well-trained professional, it

provides excellent results. An accurate diagnosis of BA

is possible if multiple US features are carefully

analyzed [52]. It is extremely useful in the diagnosis of

choledochal cysts and also in verifying the absence of

the GB, which may suggest a diagnosis of BA. US play

a role in screening patients with infantile cholestasis,

mainly focusing on the size, shape and contractility of

GB. Nevertheless, if changes in GB volume occur post-

feeding in serial US analysis, BA cannot be ruled out.

Despite difficulties in identification due to its small

volume, the contractibility of the GB in BA can be

observed in a percentage of cases due to a patent bile

duct [53]. US evaluate congenital anomalies associatedwith BA.

Triangular cord (TC)-sign which represents a cone-

shaped fibrotic mass cranial to the bifurcation of the

portal vein is also a useful diagnostic criterion [54]. The

presence of the TC-sign in the US examination has

shown to be correct in 95% of BA diagnoses, with 85%

sensitivity and 100% specificity [55]. False negative

TC-sign results may occur in some BA cases due to

hepatic radicles, such as hypoplasic or aplasic ducts or

fibrous hepatic ducts, even at early stages [56].

However, this sign does not present or cannot be foundin every patient, and it is largely dependent on

operators' techniques and experience. Furthermore, it

would be difficult to visualize TC-sign if the patient is

very young with hepatic maldevelopment or the

resolution of ultrasonic apparatus is poor [57]. A recent

study reported that TC-sign has 59.3% sensitivity and

88.9% specificity in predicting BA [43].

Abnormal GB is also an important positive pointer to

BA, but this is less reliable as an isolated finding in the

absence of other US features of BA. Abnormal GB was

observed in infants with cystic fibrosis. Infants with no

US evidence of BA will still require further investigation

to establish the cause of their conjugated

hyperbilirubinemia. Tiao et al., [58] reported that, GB

lengths < 1.5 cm had 77.4% sensitivity, 69.8%

specificity for the diagnosis of BA. This finding is in

agreement with that of El-Guindi et al., [43] who found

that GB length of less than 20.5 mm is 81.4% sensitive

and 70.3% specific for BA. In addition, non-contractile

GB had a high sensitivity (92.5%), but low specificity

(51.9%) in discriminating BA.

c. Color Doppler US

The presence of angiographically perivascula

arterial tufts in the periphery of the hepatic arteria

circulation (hepatic subcapsular flow) was reported in

patients with BA and suggested that these findings

might be useful in the diagnosis of BA [59]. ColoDoppler US was used instead of angiography to

evaluate hepatic arterial changes. On color Doppler US

images, an enlarged hepatic artery and hepatic arteria

flow that extended to the hepatic surface were seen in

all patients with BA. It had a sensitivity and specificity

of 100% and 86% respectively in predicting BA [60]. A

similar study reported that hepatic subcapsular flow

was found in 96.3% of BA group compared to 3.7% in

non-BA group with 96.3% of both sensitivity and

specificity in discriminating infants with BA from those

with non-BA [43].

Hepatic artery diameter (HAD) was found to be

significantly larger in patients with BA (2.1 0.7 mm

than in patients with non-BA (1.5 0.4 mm) (P


6/12


d. Hepatob iliary Scint igraphy

These procedures are invasive and time consuming

and do not significantly increase the accuracy of

diagnosis [62]. Normal hepatic uptake of the radiotracer

occurs within the first 10-15 minutes after injection, but

the excreted tracer reaches the duodenum within 1

hour. If there is an excellent accumulation of theradiotracer in the liver but no bowel activity at 24 hours,

the diagnosis of BA would be possible [57].

DISIDA Tc99m (Tc99m linked to 2.6-diisopropyl

imino diacetic acid) and BRIDA Tc99m isotopes

(Tc99m linked to 2.4.6-trimethyl-3-bromo imino diacetic

acid), are frequently used in radioisotope scan. They

have a very short half-life, low gamma ray emissions,

very good concentration in the liver, non-conjugated

excretion in the bile and a low renal excretion level.

The BRIDA is offering the advantage that 98% of the

dose administered is eliminated by the liver, while withDISIDA hepatic elimination is 85% [63]. The DISIDA

Tc99m test is not recommended when conjugated

bilirubin levels are over 20 mg/dl. In such cases BRIDA

Tc99m should be employed, since, even with high

levels of bilirubin, it maintains hepatic capture levels of

70%. Premature, very low birth weight newborns and

children on total parentral nutrition, even with pervious

presence of bile ducts, may not present excretion of the

radiopharmaceutical to the intestine. In these cases

there is indication to repeat examination two weeks

later [64].

For patients in whom no intestinal tracer excretion is

detected even after 24 h, scintigraphy is repeated after

giving them ursodeoxycholic acid for 4872 hrs before

the second scan and is continued till the second scan

is over. These additional procedures add to the time

and expense of diagnosis; however, the overall

specificity and accuracy in the event of a non draining

scintigraphic picture remain far from being satisfactory

[65].

Although hepatic scintigraphy showing definitebiliary excretion excludes BA, the absence of excretion

has poor predictive value because any form of severe

cholestasis may show similar findings [66]. Thus non-

excretion of radioisotope neither confirms the diagnosis

of BA, nor rules out the diagnosis of causes other than

BA [67]. Yet, hepatobiliary scintigraphy had 80%

sensitivity, 72.9% specificity, and 74.1% accuracy [68].

The diagnostic accuracy of hepatobiliary scintigraphy

has been reported to be inferior to that of liver biopsy

[35].

6.5. Liver Biopsy

In many cases, the clinical and radiographic findings

are not diagnostic and histologic findings are critical in

patient management decisions [35]. Liver biopsy cancorrectly predict extrahepatic biliary obstruction in more

than 90% of cases, directing the evaluation toward

cholangiography [69, 70]. Hepatic histology does no

differentiate patients with the embryonic and perinata

forms of BA [71].

Lee and Looi [72], reported that, the presence o

moderate to severe bile ductular proliferation (91%

was the most consistent histological feature noted in

BA with the highest sensitivity (91%) and specificity

(88%) for its diagnosis. They reported bile plugs in 70%

of their cases with 68% sensitivity and 86% specificityfor the diagnosis of BA. Rastogi et al., [34] reported

that ductular proliferation, bile plugs and portal fibrosis

emerged as the best indicators of BA. Moreover, Russo

et al., [73] found a great difference between BA and

non-BA cases where bile duct proliferation, bile plugs in

ducts and canaliculi, and the more severe grades o

portal fibrosis were in favor of BA cases. El-Guindi e

al., [43] reported that ductular proliferation had 100%

sensitivity and 88% specificity, while bile plugs had

96.3% sensitivity and 64% specificity in diagnosing BA.

6.6. Duodenal Tube Test (DTT)

A nasogastric tube is put into the distal portion o

the duodenum and the liquid collected for 24 hours. I

no bile fluid is seen, the test is prolonged for a furthe

24 hours. The enteral administration of magnesium

sulfate at 25%, with a dosage of 1 ml/kg, or I.V

cholecystokinin, can be performed when biliary fluids

are negative 24 hours after the insertion of the

duodenal tube [63].

DTT test showed a sensitivity of 97.3%, and

specificity of 93.7%, a positive predictive value o92.3% and a negative predictive value of 98.5%. DTT

is not highly invasive, it is inexpensive and it may be

performed by trained personnel with few specialized

resources. Its high sensitivity, specificity and predictive

value make it a useful tool in the differential diagnosis

of infantile cholestatic jaundice, particularly in the

diagnosis of BA [62]. The presence of bile excludes the

possibility of BA; yet, the absence of bile does no

necessarily indicate BA.


7/12

40 Global Journal o f Gastroenterology & Hepatology, 2013 Vol. 1, No. 1

Sira et a

6.7. Cholangiogr aphy

a. Endoscopic Retrograde Cholangiopancreato-graphy (ERCP)

After the application of the radiological contrast into

the papilla of Vater, it is possible to observe whether or

not there is progression through the bile and pancreatic

ducts [63]. ERCP has a sensitivity of 86 %, a specificityof 94 % in diagnosing BA [74].

b. Magnetic Resonance Cholangiopancreatography(MRCP)

MRCP is a reliable non-invasive imaging technique

for the diagnosis of BA and could help in early referrals

from pediatricians who may spend much time seeking

non-surgical causes for jaundice in infants.

Preoperative MRCP is highly recommended to avoid

unnecessary surgery in infants with cholestatic

jaundice [75]. It has been reported that a small GB by

MRCP can be considered highly suggestive of BA [76].

Periportal thickening in the MRCP image seems to

represent periportal fibrosis on histologic examination

and increased sonographic echo in the periportal area

[77]. MRCP is more expensive than hepatobiliary

scintigraphy and not available in all hospitals. One of

the vulnerable points of MRCP is that it does not show

the bile flow itself as does hepatobiliary scintigraphy or

ERCP [75].

c. Intra-Operative Cholangiograpy (IOC)

IOC is performed when other methods do not permita definitive diagnosis. As patients with intrahepatic

cholestasis may have their condition aggravated by

anesthetic products, hemodynamic alterations and

infections, the investigation which precedes IOC should

be as thorough as possible, in an attempt to achieve a

non-invasive diagnosis. IOC should be performed at a

medical center which is capable of performing the

hepatoportoenterostomy immediately if necessary [44].

IOC is the gold-standard for the diagnosis of BA.

However, the rate of negative laparotomy findings

without preoperative liver biopsy is much higher than

that with a preoperative liver biopsy (28% vs. 11%).

Biopsy and IOC, both invasive procedures, become

essential in such cases to confirm the diagnosis.

Among the 3 commonly used tests in NC (US,

hepatobiliary scintigraphy, and liver biopsy), liver

biopsy is the most accurate but most invasive test [65].

6.8. Diagnost ic Laparoscopy

A coarse, irregular, greenish-brown liver with some

degree of fine angiomatous development and an atretic

GB were found laparoscopically in some infants with

BA. However, in case of neonatal hepatitis, the live

was smooth, sharp-edged, and chocolate brown in

color and simultaneous cholangiography showed the

passage of the contrast material into the proxima

biliary tract and the intestinal system. Laparoscopic

guided puncturing with a needle was used to wash the

bile duct from the GB to decrease jaundice in patientswith inspissated bile syndrome, thus unnecessary

laparotomy was avoided in 25% of the patients [57].

7. DIFFERENTIAL DIAGNOSIS

A major challenge in NC is to differentiate BA from

other non-atretic causes. In developing countries there

are considerable problems of late referral of NC cases

and performing surgery without prelaparotomy live

biopsy that contributes to a high proportion of negative

laparotomy and increased morbidity [34].

Medical causes of NC must be excluded [3]. The

main differential diagnosis of a biliary obstructive

pattern in a liver biopsy of a cholestatic infant includes

choledochal cysts, bile duct strictures, alpha-1

antitrypsin deficiency, total parentral nutrition

associated cholestasis, cystic fibrosis, progressive

familial intrahepatic cholestasis type 3, North American

Indian childhood cirrhosis (cirhin deficiency), Alagille

syndrome [78], CMV hepatitis and inspissated bile

syndrome.

8. MANAGEMENT

8.1. Surgical Management

The current surgical management of BA patients

involves two steps: Kasai operation (in the neonata

period), which aims to restore bile flow and LTx in

children for whom the Kasai operation has failed in its

primary aim or for whom complications of biliary

cirrhosis have supervened [3].

a. Kasai Operation (Hepatoporto-Enterostomy)

There is an increased need for early and correc

diagnosis of BA because timely surgica

portoenterostomy is necessary for improved biliary

drainage. Kasai procedures appear to have the bes

outcome in children younger than 60 to 80 days [79]

The Kasai operation is an accepted method o

achieving bile drainage in BA [80]. Reports from

several institutions in Japan show that more than 80%

of BA patients become jaundice-free after the Kasa

operation. A favorable course depends essentially on

early surgical intervention [81]. However, progressive


8/12


liver disease develops in a few patients with successful

Kasai operations and LTx is needed for patients with

frequent postoperative cholangitis and for those with

liver cirrhosis [82].

Clinical outcomes after the Kasai operation can be

divided into three categories; patients who continue in

a jaundice-free state and reach adulthood with fewmanifestations of liver disease and portal hypertension;

patients who continue in a jaundice-free state but

whose quality of life is impaired because of some

manifestations of liver disease owing to ongoing

cirrhosis, and who thus need follow-up in planning LTx,

and finally patients whose disease process continues,

leading to death from cholestatic liver failure within the

first two years of life unless successful LTx is achieved

[80]. If the Kasai operation succeeds in restoring bile

flow, the stools become colored and jaundice fades.

The evolution of the biliary cirrhosis is prevented or at

least delayed. Survival with the native liver has beenreported up to adulthood [3].

The most common complications following the

Kasai procedure include ascending cholangitis which

occurs in the first weeks or months after the Kasai

procedure in 30%-60% of cases [3]. Portal

hypertension occurs in at least two-thirds of the

children after porto-enterostomy, even in those with

complete restoration of bile flow [83]. Hepatopulmonary

syndrome and pulmonary hypertension may occur

leading to hypoxia, cyanosis, dyspnea and digital

clubbing [3]. Hepatocarcinomas, hepatoblastomas [84]

and cholangiocarcinoma [85] have been described in

the cirrhotic livers of patients with BA. Screening for

malignancy has to be performed regularly in the follow-

up of patients who underwent a successful Kasai

operation [3].

b. Liver Transplantation

Indications for LTx depend on the success of Kasai

portoenterostomy and the rate of development of

complications. In infants in whom bile drainage is not

achieved, LTx is usually indicated within 6 months to 2

years of age. However, in those who have had a

successful procedure, LTx should be considered in the

presence of cirrhosis with hepatic dysfunction, or

development of portal hypertension with ascites and

variceal bleeding unresponsive to endoscopic

management [86].

Investigation of factors that predict the need for LTx

help with planning and counseling of families. Such

factors are the concentration of bilirubin at 30 days

after surgery and a pediatric end-stage liver disease

score approach [87]. In children with the syndromic

variants of BA, associated anomalies, especially

congenital cardiac malformations, increase the risk o

both early mortality and morbidity [88].

With advances in surgical techniques and

management, children with BA after LTx can achievesatisfactory survival, although there remains a high risk

of complications in the early postoperative period [89].

8.2. Adjuvant Therapy

Effective postsurgical management includes

prevention and treatment of complications such as

cholangitis and provision of effective nutritional and

family support [88]. Prophylactic antibiotics (to preven

cholangitis) and choleretic agents are commonly

prescribed, although definitive evidence supporting

their use is lacking [90]. All infants should havesupplementation of nutrition and fat-soluble vitamins

(A, D, E, and K) to prevent malnutrition, overcome fa

malabsorption and reduce the effects of excess

catabolism. In refractory cases, parenteral vitamins

might be needed. Steatorrhoea from fat malabsorption

can be managed by provision of between 40% and

60% of fat in the feed as medium-chain triglycerides

[91]. Supplementation should contain high-energy

high-protein feed that provides between 110160% o

the recommended daily amount [88].

9. PROGNOSIS OF BA

Several prognostic factors have been identified in

BA patients. Some of them are related to

characteristics of the disease. The prognosis of the

Kasai operation is worse when BA is associated with a

polysplenia syndrome [92], when macroscopic

obstructive lesions of extra-hepatic biliary remnant are

diffuse (prognosis worsens from type 1 to type 3) [3]

when histological obliteration of the bile ducts

(especially at porta hepatis) is more severe and when

liver fibrosis is more extensive at the time of the Kasa

operation [93]. Other prognostic factors are related tothe management of BA patients and can be improved

[3]. The four year survival with native liver after Kasa

operation is 43%-51% and the four year survival afte

LTx is 89%-90% [94].

10. CONCLUSION

In spite of the rare incidence of BA, it represents

about one third of all NC. Effective treatment largely

depends on early diagnosis and discrimination from


9/12


other causes of cholestasis. Clinical, laboratory,

radiological and histopathological parameters are all

helpful in diagnosis, yet, no single parameter is 100%

diagnostic. So they are all helpful but not conclusive

leaving IOC as the gold-standard for diagnosis.

Combining different parameters may improve

predictability and early diagnosis of BA and decrease

the need for the invasive IOC.

CONFLICT OF INTERESTS

The authors declare that they have no competing

interests.

ABBREVIATIONS

BA = Biliary atresia

BRIDA Tc99m = Tc99m linked to 2.4.6-trimethyl-3-

bromo imino diacetic acid

CMV = Cytomegalovirus

DISIDA Tc99m = Tc99m linked to 2.6-diisopropyl

imino diacetic acid

DPM = Ductal plate malformation

DTT = Duodenal tube test

ERCP = Endoscopic retrograde cholangio-

pancreatography

GB = Gallbladder

GGT = Gamma glutamyl transpeptidase

HAD = Hepatic artery diameter

Hnf6 = Hepatocyte nuclear factor 6

IOC = Intraoperative cholangiography

MRCP = Magnetic resonance cholangiopan-

creatography

NC = Neonatal cholestasis

TC = Triangular cord

US = Ultrasonography

REFERENCES

[1] Tainaka T, Kaneko K, Nakamura S, Ono Y, Sumida W, Ando

H. Histological assessment of bile lake formation afterhepatic portoenterostomy for biliary atresia. Pediatr Surg Int2008; 24(3): 265-9.http://dx.doi.org/10.1007/s00383-007-2099-z

[2] Bazlul Karim AS, Kamal M. Cholestatic jaundice during

infancy: experience at a tertiary-care center in BangladeshIndian J Gastroenterol 2005; 24(2): 52-4.

[3] Chardot C. Biliary atresia. Orphanet J Rare Dis 2006; 128.

[4] Hsiao CH, Chang MH, Chen HL, et al.Universal screeningfor biliary atresia using an infant stool color card in TaiwanHepatology 2008; 47(4): 1233-40.http://dx.doi.org/10.1002/hep.22182

[5] Wada H, Muraji T, Yokoi A, et al.Insignificant seasonal and

geographical variation in incidence of biliary atresia in Japana regional survey of over 20 years. J Pediatr Surg 200742(12): 2090-2.http://dx.doi.org/10.1016/j.jpedsurg.2007.08.035

[6] Schreiber RA, Kleinman RE. Genetics, immunology, andbiliary atresia: an opening or a diversion? J PediatGastroenterol Nutr 1993; 16(2): 111-3.http://dx.doi.org/10.1097/00005176-199302000-00001

[7] Davenport M, Dhawan A. Epidemiologic study of infants wit

biliary atresia. Pediatrics 1998; 101(4 Pt 1): 729-30.http://dx.doi.org/10.1542/peds.101.4.729a

[8] Carmi R, Magee CA, Neill CA, Karrer FM. Extrahepatic biliaratresia and associated anomalies: etiologic heterogeneity

suggested by distinctive patterns of associations. Am J MedGenet 1993; 45(6): 683-93.http://dx.doi.org/10.1002/ajmg.1320450606

[9] Sokol RJ, Shepherd RW, Superina R, Bezerra JA, Robuck PHoofnagle JH. Screening and outcomes in biliary atresia

summary of a National Institutes of Health workshopHepatology 2007; 46(2): 566-81.http://dx.doi.org/10.1002/hep.21790

[10] Wildhaber BE. Biliary atresia: 50 years after the first kasaISRN surgery 2012; 2012132089.

[11] Chardot C, Carton M, Spire-Bendelac N, Le Pommelet C

Golmard JL, Auvert B. Epidemiology of biliary atresia inFrance: a national study 1986-96. J Hepatol 1999; 31(6)1006-13.http://dx.doi.org/10.1016/S0168-8278(99)80312-2

[12] Bezerra JA, Tiao G, Ryckman FC, et al.Genetic induction o

proinflammatory immunity in children with biliary atresiaLancet 2002; 360(9346): 1653-9.

http://dx.doi.org/10.1016/S0140-6736(02)11603-5

[13] Sokol RJ, Mack C, Narkewicz MR, Karrer FM. Pathogenesis

and outcome of biliary atresia: current concepts. J PediatGastroenterol Nutr 2003; 37(1): 4-21.http://dx.doi.org/10.1097/00005176-200307000-00003

[14] Davenport M, Gonde C, Redkar R, et aImmunohistochemistry of the liver and biliary tree in

extrahepatic biliary atresia. J Pediatr Surg 2001; 36(7): 101725.http://dx.doi.org/10.1053/jpsu.2001.24730

[15] Huang YH, Chou MH, Du YY, et al. Expression of toll-like

receptors and type 1 interferon specific protein MxA in biliaryatresia. Lab Invest 2007; 87(1): 66-74.http://dx.doi.org/10.1038/labinvest.3700490

[16] Fjaer RB, Bruu AL, Nordbo SA. Extrahepatic bile duct atresi

and viral involvement. Pediatr Transplant 2005; 9(1): 68-73.http://dx.doi.org/10.1111/j.1399-3046.2005.00257.x

[17] Domiati-Saad R, Dawson DB, Margraf LR, Finegold MJWeinberg AG, Rogers BB. Cytomegalovirus and humanherpesvirus 6, but not human papillomavirus, are present in

neonatal giant cell hepatitis and extrahepatic biliary atresiaPediatr Dev Pathol 2000; 3(4): 367-73.http://dx.doi.org/10.1007/s100240010045

[18] HH AK, Nowicki MJ, Kuramoto KI, Baroudy B, Zeldis JBBalistreri WF. Evaluation of the role of hepatitis C virus in

biliary atresia. Pediatr Infect Dis J 1994; 13(7): 657-9.http://dx.doi.org/10.1097/00006454-199407000-00015


10/12


[19] Zong Y, Stanger BZ. Molecular mechanisms of liver and bile

duct development. Wiley Interdisciplinary Reviews: Dev Biol2012; 1(5): 643-55.http://dx.doi.org/10.1002/wdev.47

[20] Leyva-Vega M, Gerfen J, Thiel BD, et al.Genomic alterationsin biliary atresia suggest region of potential disease

susceptibility in 2q37.3. Am J Med Genet A 2010; 152A(4):886-95.http://dx.doi.org/10.1002/ajmg.a.33332

[21] Garcia-Barcelo MM, Yeung MY, Miao XP, et al. Genome-wide association study identifies a susceptibility locus forbiliary atresia on 10q24.2. Human Mol Genet 2010; 19(14):2917-25.http://dx.doi.org/10.1093/hmg/ddq196

[22] Huang CC, Chuang JH, Chou MH, et al. Matrilysin (MMP-7)

is a major matrix metalloproteinase upregulated in biliaryatresia-associated liver fibrosis. Mod Pathol 2005; 18(7):941-50.http://dx.doi.org/10.1038/modpathol.3800374

[23] HH AK, El-Ayyouti M, Hawas S, et al. HLA in Egyptianchildren with biliary atresia. J Pediatr 2002; 141(3): 432-3.http://dx.doi.org/10.1067/mpd.2002.127506

[24] Irie N, Muraji T, Hosaka N, Takada Y, Sakamoto S, TanakaK. Maternal HLA class I compatibility in patients with biliary

atresia. J Pediatr Gastroenterol Nutr 2009; 49(4): 488-92.

http://dx.doi.org/10.1097/MPG.0b013e31819a4e2c

[25] Kahn E. Biliary atresia revisited. Pediatr Dev Pathol 2004;7(2): 109-24.http://dx.doi.org/10.1007/s10024-003-0307-y

[26] Ghoneim EM, Sira MM, Abd Elaziz AM, Khalil FO, Sultan

MM, Mahmoud AB. Diagnostic value of hepatic intercellularadhesion molecule-1 expression in Egyptian infants withbiliary atresia and other forms of neonatal cholestasis.

Hepatology Research: The Official Journal of the JapanSociety of Hepatology 2011; 41(8): 763-75.

[27] Sira MM, El-Guindi MA, Saber MA, Ehsan NA, Rizk MS.Differential hepatic expression of CD56 can discriminatebiliary atresia from other neonatal cholestatic disorders. Eur J

Gastroenterol Hepatol 2012; 24(10): 1227-33.http://dx.doi.org/10.1097/MEG.0b013e328356aee4

[28] Klippel CH. A new theory of biliary atresia. J Pediatr Surg1972; 7(6): 651-4.http://dx.doi.org/10.1016/0022-3468(72)90274-6

[29] Ho CW, Shioda K, Shirasaki K, Takahashi S, Tokimatsu S,

Maeda K. The pathogenesis of biliary atresia: amorphological study of the hepatobiliary system and thehepatic artery. J Pediatr Gastroenterol Nutr 1993; 16(1): 53-

60.http://dx.doi.org/10.1097/00005176-199301000-00010

[30] Schmidt C, Bladt F, Goedecke S, et al. Scatterfactor/hepatocyte growth factor is essential for liverdevelopment. Nature 1995; 373(6516): 699-702.

http://dx.doi.org/10.1038/373699a0

[31] Suskind DL, Rosenthal P, Heyman MB, et al. Maternal

microchimerism in the livers of patients with biliary atresia.BMC Gastroenterol 2004; 414.

[32] Muraji T, Hosaka N, Irie N, et al.Maternal microchimerism inunderlying pathogenesis of biliary a tresia: quantification andphenotypes of maternal cells in the liver. Pediatrics 2008;

121(3): 517-21.http://dx.doi.org/10.1542/peds.2007-0568

[33] Harper P, Plant JW, Unger DB. Congenital biliary atresia andjaundice in lambs and calves. Aust Vet J 1990; 67(1): 18-22.http://dx.doi.org/10.1111/j.1751-0813.1990.tb07385.x

[34] Rastogi A, Krishnani N, Yachha SK, Khanna V, Poddar U,Lal R. Histopathological features and accuracy for

diagnosing biliary atresia by prelaparotomy liver biopsy indeveloping countries. J Gastroenterol Hepatol 2009; 24(1):97-102.http://dx.doi.org/10.1111/j.1440-1746.2008.05737.x

[35] Dehghani SM, Haghighat M, Imanieh MH, Geramizadeh B

Comparison of different diagnostic methods in infants withCholestasis. World J Gastroenterol 2006; 12(36): 5893-6.

[36] Powell JE, Keffler S, Kelly DA, Green A. Populationscreening for neonatal liver disease: potential for acommunity-based programme. J Med Screen 2003; 10(3)

112-6.http://dx.doi.org/10.1258/096914103769010996

[37] Chen SM, Chang MH, Du JC, et al. Screening for biliary

atresia by infant stool color card in Taiwan. Pediatrics 2006117(4): 1147-54.http://dx.doi.org/10.1542/peds.2005-1267

[38] Lien TH, Chang MH, Wu JF, et al.Effects of the infant stoocolor card screening program on 5-year outcome of biliaryatresia in Taiwan. Hepatology 2011; 53(1): 202-8.http://dx.doi.org/10.1002/hep.24023

[39] Tseng JJ, Lai MS, Lin MC, Fu YC. Stool color card screeningfor biliary atresia. Pediatrics 2011; 128(5): e1209-15.http://dx.doi.org/10.1542/peds.2010-3495

[40] Redkar R, Davenport M, Howard ER. Antenatal diagnosis ocongenital anomalies of the biliary tract. J Pediatr Surg 1998

33(5): 700-4.http://dx.doi.org/10.1016/S0022-3468(98)90190-7

[41] Mirza B, Iqbal S, Sheikh A. Biliary atresia associated withpolysplenia syndrome, situs inversus abdominus, and

reverse rotation of intestine. APSP J Case Reports 20123(2): 14.

[42] Poddar U, Thapa BR, Das A, Bhattacharya A, Rao KL, SingK. Neonatal cholestasis: differentiation of biliary atresia fromneonatal hepatitis in a developing country. Acta Paediat

2009; 98(8): 1260-4.http://dx.doi.org/10.1111/j.1651-2227.2009.01338.x

[43] El-Guindi MA, Sira MM, Konsowa HA, El-Abd OL, Salem TAValue of hepatic subcapsular flow by color doppleultrasonography in the diagnosis of biliary atresia.

Gastroenterol Hepatol 2013.http://dx.doi.org/10.1111/jgh.12151

[44] Cauduro S. Extra-hepatic biliary atresia:diagnostic methodsJ Pediatr 2003; 79(2): 107-14.

[45] Giannattasio A, Cirillo F, Liccardo D, Russo M, Vallone G

Iorio R. Diagnostic role of US for biliary atresia. Radiology2008; 247(3): 912; author reply-3.

[46] Fitzgerald J. Distrbios colestticos do lactente. J Clin PedAmer Norte 1988; 35375-91.

[47] Matsui A, Fujimoto T, Takazawa Y, Okaniwa M, KamoshitaS. Serum bile acid levels in patients with extrahepatic biliaryatresia and neonatal hepatitis during the first 10 days of life

J Pediatr 1985; 107(2): 255-7.http://dx.doi.org/10.1016/S0022-3476(85)80140-2

[48] Gustafsson J, Alvelius G, Bjorkhem I, Nemeth A. Bile acidmetabolism in extrahepatic biliary atresia: lithocholic acid i

stored dried blood collected at neonatal screening. Ups JMed Sci 2006; 111(1): 131-6.http://dx.doi.org/10.3109/2000-1967-017

[49] Hasegawa T, Sasaki, Kimura T, et al.Measurement of serum

hyaluronic acid as a sensitive marker of liver fibrosis in biliaryatresia. J Pediatr Surg 2000; 35(11): 1643-6.http://dx.doi.org/10.1053/jpsu.2000.18342

[50] Sasaki F, Hata Y, Hamada H, Takahashi H, Uchino JLaminin and procollagen-III-peptide as a serum marker fo

hepatic fibrosis in congenital biliary atresia. J Pediatr Surg1992; 27(6): 700-3.http://dx.doi.org/10.1016/S0022-3468(05)80094-6

[51] Kobayashi H, Miyano T, Horikoshi K, Tokita A. Prognostivalue of serum procollagen III peptide and type IV collagen in

patients with biliary atresia. J Pediatr Surg 1998; 33(1): 1124.http://dx.doi.org/10.1016/S0022-3468(98)90374-8


11/12


[52] Humphrey TM, Stringer MD. Biliary atresia: US diagnosis.

Radiology 2007; 244(3): 845-51.http://dx.doi.org/10.1148/radiol.2443061051

[53] Choi SO, Park WH, Lee HJ, Woo SK. 'Triangular cord': asonographic finding applicable in the diagnosis of biliaryatresia. J Pediatr Surg 1996; 31(3): 363-6.http://dx.doi.org/10.1016/S0022-3468(96)90739-3

[54] Tan Kendrick A, Phua K, Ooi B, Subramaniam R, Tan C,Goh A. Making the diagnosis of biliary atresia using the

triangular cord sign and Gall bladder length. Pediatr Radiol2000; 3069-73.

[55] Park WH, Choi SO, Lee HJ. Technical innovation for

noninvasive and early diagnosis of biliary atresia: theultrasonographic "triangular cord" sign. J HepatobiliaryPancreat Surg 2001; 8(4): 337-41.http://dx.doi.org/10.1007/s005340170005

[56] Visrutaratna P, Wongsawasdi L, Lerttumnongtum P,Singhavejsakul J, Kattipattanapong V, Ukarapol N.Triangular cord sign and ultrasound features of the gall

bladder in infants with biliary atresia. Australas Radiol 2003;47(3): 252-6.http://dx.doi.org/10.1046/j.1440-1673.2003.01172.x

[57] Tang ST, Ruan QL, Cao ZQ, Mao YZ, Wang Y, Li SW.Diagnosis and treatment of biliary atresia: a retrospectivestudy. Hepatobiliary Pancreat Dis Int 2005; 4(1): 108-12.

[58] Tiao MM, Chuang JH, Huang LT, et al. Management ofbiliary atresia: experience in a single institute. Chang GungMed J 2007; 30(2): 122-7.

[59] Uflacker R, Pariente DM. Angiographic findings in biliaryatresia. Cardiovasc Intervent Radiol 2004; 27(5): 486-90.http://dx.doi.org/10.1007/s00270-004-2636-2

[60] Lee MS, Kim MJ, Lee MJ, et al.Biliary atresia: color doppler

US findings in neonates and infants. Radiology 2009; 252(1):282-9.http://dx.doi.org/10.1148/radiol.2522080923

[61] Kim WS, Cheon JE, Youn BJ, et al.Hepatic arterial diameter

measured with US: adjunct for US diagnosis of biliary atresia.Radiology 2007; 245(2): 549-55.http://dx.doi.org/10.1148/radiol.2452061093

[62] Larrosa-Haro A, Caro-Lopez AM, Coello-Ramirez P, Zavala-

Ocampo J, Vazquez-Camacho G. Duodenal tube test in thediagnosis of biliary atresia. J Pediatr Gastroenterol Nutr2001; 32(3): 311-5.http://dx.doi.org/10.1097/00005176-200103000-00015

[63] Shah HA, Spivak W. Neonatal cholestasis. New approaches

to diagnostic evaluation and therapy. Pediatr Clin North Am1994; 41(5): 943-66.

[64] Spivak W, Sarkar S, Winter D, Glassman M, Donlon E,Tucker KJ. Diagnostic utility of hepatobiliary scintigraphy with99mTc-DISIDA in neonatal cholestasis. J Pediatr 1987;

110(6): 855-61.http://dx.doi.org/10.1016/S0022-3476(87)80396-7

[65] Poddar U, Bhattacharya A, Thapa BR, Mittal BR, Singh K.Ursodeoxycholic acid-augmented hepatobiliary scintigraphy

in the evaluation of neonatal jaundice. J Nucl Med 2004;45(9): 1488-92.

[66] Liu CS, Chin TW, Wei CF. Value of gamma-glutamyltranspeptidase for early diagnosis of biliary atresia.Zhonghua Yi Xue Za Zhi (Taipei) 1998; 61(12): 716-20.

[67] Yachha SK. Cholestatic jaundice during infancy. Indian JGastroenterol 2005; 24(2): 47-8.

[68] Imanieh MH, Dehghani SM, Bagheri MH, et al. Triangularcord sign in detection of biliary atresia: is it a valuable sign?

Digestive Dis Sci 2010; 55(1): 172-5.http://dx.doi.org/10.1007/s10620-009-0718-3

[69] Mack CL, Sokol RJ. Unraveling the pathogenesis andetiology of biliary atresia. Pediatr Res 2005; 57(5 Pt 2): 87R-94R.http://dx.doi.org/10.1203/01.PDR.0000159569.57354.47

[70] Moyer V, Freese DK, Whitington PF, et al.Guideline for the

evaluation of cholestatic jaundice in infantsrecommendations of the North American Society for PediatriGastroenterology, Hepatology and Nutrition. J Pediat

Gastroenterol Nutr 2004; 39(2): 115-28.http://dx.doi.org/10.1097/00005176-200408000-00001

[71] Davenport M, Tizzard SA, Underhill J, Mieli-Vergani GPortmann B, Hadzic N. The biliary atresia splenicmalformation syndrome: a 28-year single-cente

retrospective study. J Pediatr 2006; 149(3): 393-400.http://dx.doi.org/10.1016/j.jpeds.2006.05.030

[72] Lee WS, Looi LM. Usefulness of a scoring system in theinterpretation of histology in neonatal cholestasis. World J

Gastroenterol 2009; 15(42): 5326-33.http://dx.doi.org/10.3748/wjg.15.5326

[73] Russo P, Magee JC, Boitnott J, et al.Design and validationof the biliary atresia research consortium histologiassessment system for cholestasis in infancy. Clinica

Gastroenterology and Hepatology: The Official ClinicaPractice Journal of the American GastroenterologicaAssociation 2011; 9(4): 357-62 e2.

[74] Keil R, Snajdauf J, Rygl M, et al.Diagnostic efficacy of ERCP

in cholestatic infants and neonates--a retrospective study ona large series. Endoscopy 2010; 42(2): 121-6.http://dx.doi.org/10.1055/s-0029-1215372

[75] Han SJ, Kim MJ, Han A, et al. Magnetic resonancecholangiography for the diagnosis of biliary atresia. J Pediat

Surg 2002; 37(4): 599-604.http://dx.doi.org/10.1053/jpsu.2002.31617

[76] Jaw TS, Kuo YT, Liu GC, Chen SH, Wang CK. MRcholangiography in the evaluation of neonatal cholestasisRadiology 1999; 212(1): 249-56.

[77] Park WH, Choi SO, Lee HJ, Kim SP, Zeon SK, Lee SL. A

new diagnostic approach to biliary atresia with emphasis onthe ultrasonographic triangular cord sign: comparison oultrasonography, hepatobiliary scintigraphy, and liver needle

biopsy in the evaluation of infantile cholestasis. J PediatSurg 1997; 32(11): 1555-9.http://dx.doi.org/10.1016/S0022-3468(97)90451-6

[78] Perlmutter DH, Shepherd RW. Extrahepatic biliary atresia: adisease or a phenotype? Hepatology 2002; 35(6): 1297-304.http://dx.doi.org/10.1053/jhep.2002.34170

[79] Petersen C. Pathogenesis and treatment opportunities fobiliary atresia. Clin Liver Dis 2006; 10(1): 73-88, vi.http://dx.doi.org/10.1016/j.cld.2005.10.001

[80] Uchida K, Urata H, Suzuki H, et al.Predicting factor of qualityof life in long-term jaundice-free survivors after the Kasa

operation. J Pediatr Surg 2004; 39(7): 1040-4.http://dx.doi.org/10.1016/j.jpedsurg.2004.03.055

[81] Petersen C, Ure BM. What's new in biliary atresia? Eur JPediatr Surg 2003; 13(1): 1-6.http://dx.doi.org/10.1055/s-2003-38294

[82] Okada T, Itoh T, Sasaki F, Honda S, Naito S, Todo S. CD56

immunostaining of the extrahepatic biliary tree as anindicator of clinical outcome in biliary atresia: a preliminaryreport. Turk J Pediatr 2008; 50(6): 542-8.

[83] Sasaki T, Hasegawa T, Nakajima K, et al. Endoscopi

variceal ligation in the management of gastroesophageavarices in postoperative biliary atresia. J Pediatr Surg 199833(11): 1628-32.http://dx.doi.org/10.1016/S0022-3468(98)90595-4

[84] Tatekawa Y, Asonuma K, Uemoto S, Inomata Y, Tanaka K

Liver transplantation for biliary atresia associated withmalignant hepatic tumors. J Pediatr Surg 2001; 36(3): 436-9.http://dx.doi.org/10.1053/jpsu.2001.21600

[85] Kulkarni PB, Beatty E Jr. Cholangiocarcinoma associate

with biliary cirrhosis due to congenital biliary atresia. Am JDis Child 1977; 131(4): 442-4.


12/12


[86] Kobayashi K, Kubota M, Okuyama N, Hirayama Y,

Watanabe M, Sato K. Mother-to-daughter occurrence ofbiliary atresia: a case report. J Pediatr Surg 2008; 43(8):1566-8.http://dx.doi.org/10.1016/j.jpedsurg.2008.03.051

[87] Cowles RA, Lobritto SJ, Ventura KA, et al. Timing of liver

transplantation in biliary atresia-results in 71 childrenmanaged by a multidisciplinary team. J Pediatr Surg 2008;43(9): 1605-9.http://dx.doi.org/10.1016/j.jpedsurg.2008.04.012

[88] Hartley JL, Davenport M, Kelly DA. Biliary atresia. Lancet2009; 374(9702): 1704-13.http://dx.doi.org/10.1016/S0140-6736(09)60946-6

[89] Sun LY, Yang YS, Zhu ZJ, et al.Outcomes in children withbiliary atresia following liver transplantation. Hepatobiliary

Pancreat Dis Int 2013; 12(2): 143-8.http://dx.doi.org/10.1016/S1499-3872(13)60023-5

[90] Arvay JL, Zemel BS, Gallagher PR, et al.Body compositionof children aged 1 to 12 years with biliary atresia or Alagille

syndrome. J Pediatr Gastroenterol Nutr 2005; 40(2): 146-50.http://dx.doi.org/10.1097/00005176-200502000-00012

[91] Baker A, Stevenson R, Dhawan A, Goncalves I, Socha P

Sokal E. Guidelines for nutritional care for infants withcholestatic liver disease before liver transplantation. PediatTransplant 2007; 11(8): 825-34.http://dx.doi.org/10.1111/j.1399-3046.2007.00792.x

[92] Chardot C, Carton M, Spire-Bendelac N, Le Pommelet C

Golmard JL, Auvert B. Prognosis of biliary atresia in the eraof liver transplantation: French national study from 1986 to1996. Hepatology 1999; 30(3): 606-11.http://dx.doi.org/10.1002/hep.510300330

[93] Wildhaber BE, Coran AG, Drongowski RA, et al.The Kasaportoenterostomy for biliary atresia: A review of a 27-yeaexperience with 81 patients. J Pediatr Surg 2003; 38(10)

1480-5.http://dx.doi.org/10.1016/S0022-3468(03)00499-8

[94] Davenport M, De Ville de Goyet J, Stringer MD, et aSeamless management of biliary atresia in England andWales (1999-2002). Lancet 2004; 363(9418): 1354-7.http://dx.doi.org/10.1016/S0140-6736(04)16045-5

Received on 16-04-2013 Accepted on 13-05-2013 Published on 25-06-2013

http://dx.doi.org/10.12970/2308-6483.2013.01.01.6

2013 Sira et al.; Licensee Synergy Publishers.This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License(http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction inany medium, provided the work is properly cited.

atresia bilier 1.pdf

Documents

Transcript of atresia bilier 1.pdf