C H A P T E R 4 3 
Biliary Atresia
Atsuyuki Yamataka  •  Joel Cazares  •  Takeshi Miyano
Biliary atresia is a relatively rare obstructive condition of
the bile ducts causing neonatal jaundice. There is a vari-
able incidence around the world (eg, Europe, 1 in 18,000
live births; France, 1 in 19,500 live births; the UK and
Ireland, 1 in 16,700 live births; Sweden, 1 in 14,000 live
births; and Japan, 1 in 9640 live births),1–6 with the highest
recorded incidence in French Polynesia (1 in 3124 live
births).7 There is a slight female predominance.
Biliary atresia first appeared as a distinct entity in the
Edinburgh Medical Journal in 1891.8 The concept of
‘correctable’ and ‘noncorrectable’ forms was introduced
in 1916.9 Despite the first successful surgical treatment
for the correctable type being reported in 1928, there
were only a few long-term survivors over the next three
decades, all with the correctable type.10–12
In the 1950s and 60s, a variety of procedures for ‘non-
correctable’ disease were developed, but none provided
consistent biliary decompression.13–17 Also, the timing of
operative intervention was controversial, with reports of
‘spontaneous’ cures, and second-look explorations for the
rather mystical belief that a totally fibrotic extrahepatic
ductal system might subsequently become patent.18–22
In 1959, the now common Kasai hepatic portoenter-
ostomy procedure was first described and ended a long,
hopeless era for patients with the noncorrectable-type
disease.23 Kasai’s original report was in Japanese and
received little attention until it was published in English
in 1968.24 Although effective bile drainage could be
achieved after portoenterostomy in about 50% of patients,
early repair was crucial and needed to be performed
before the age of 2 months. Conversely, effective bile
drainage was observed in only 7% of patients if correc-
tion was performed after the age of 4 months.25 Kasai’s
portoenterostomy procedure gradually gained popularity
in the USA, and by the 1990s, more than 90% of infants
with biliary atresia had undergone this procedure.26
Since liver transplantation has become a viable treat-
ment option for liver failure in the pediatric population,
biliary atresia has become the most common indication
for liver transplantation in children. Infants whose jaun-
dice does not resolve after portoenterostomy, or those
with complications associated with end-stage chronic
liver disease related to biliary atresia, will usually require
liver transplantation within the first few years of life.
The combination of hepatic portoenterostomy and
liver transplantation has transformed a disease that was
nearly universally fatal in the 1960s into one with an
overall five-year survival of about 90%. Despite the
debate over whether hepatic portoenterostomy or primary
liver transplantation should be performed as the initial
procedure for biliary atresia, the consensus among
580
pediatric surgeons around the world is that hepatic por-
toenterostomy is the most reasonable first choice.
Recently, the authors had an opportunity to review an
original video of Professor Kasai performing his own
portoenterostomy.27 Interestingly, his original portal dis-
section was actually quite shallow and limited, resulting
in a narrow portoenterostomy anastomosis, with sutures
placed shallowly at 2 and 10 o’clock where the native
right and left bile ducts would have been, probably to
minimize microscopic bile duct injury. Although not sup-
ported by research, the original technique as performed
by Kasai may result in superior outcomes as it focuses
specifically on the physiologic and anatomic characteris-
tics of the liver in biliary atresia. The authors currently
perform a modified version of Kasai’s original portoen-
terostomy (KOPE) using the minimally invasive approach.
PATHOGENESIS
Various etiologic mechanisms for biliary atresia have
been postulated, including intrauterine or perinatal viral
infection, genetic mutations, abnormal ductal plate
remodeling, vascular or metabolic insult to the develop-
ing biliary tree, pancreaticobiliary ductal malunion, and
immunologically mediated inflammation. However,
despite intensive interest and investigation, the cause of
biliary atresia remains unknown and there is no ideal
animal model.
There are syndromic and nonsyndromic forms of
biliary atresia.28 Syndromic biliary atresia (also known as
the embryonic type) is associated with other congenital
anomalies, including interrupted inferior vena cava,
preduodenal portal vein, intestinal malrotation, situs
inversus, cardiac defects, and polysplenia.29 Syndromic
biliary atresia accounts for 10–20% of all cases, and is
likely to be due to a developmental insult occurring
during differentiation of the hepatic diverticulum from
the foregut of the embryo. A possible relation between
syndromic biliary atresia and maternal diabetes has been
reported.28 Nonsyndromic biliary atresia (also known as
the perinatal type) may have its origins later in gestation,
and may have a different clinical course, with biliary
obstruction being progressive.
Reovirus type 3 infection, rotavirus, cytomegalovirus
(CMV), papillomavirus, and Epstein–Barr virus have all
been proposed as possible etiologic agents, but conclusive
evidence is lacking. In one report, CMV infection was
found in four of ten patients with biliary atresia,30 and
reovirus infection has been found in the livers of up to
55% of biliary atresia patients versus 10–20% in a control

group.31 The identification of viruses in children with
biliary atresia is inconsistent in the literature, and several
viruses have been used to create animal models that may
be valuable for assessing the pathogenesis and treatment
of biliary atresia.
Generally, biliary atresia is not considered an inherited
disorder. However, genetic mutations that result in defec-
tive morphogenesis may be important in syndromic
biliary atresia. Transgenic mice with a recessive deletion
of the inversin gene have situs inversus and an inter-
rupted extrahepatic biliary tree.32 Mutations of the CFC1
gene, which is involved in left–right axis determination
in humans, have been identified in a few patients with
syndromic biliary atresia.33 The importance of the mac-
rophage migration inhibitory factor gene, which is a
pleiotropic lymphocyte and macrophage cytokine in
biliary atresia pathogenesis, has also been reported.34
Other studies have identified abnormalities in laterality
genes in a small number of patients with biliary atresia,
including the transcription factor ZIC3.35 A high inci-
dence of polymorphic variants in the jagged-1, keratin-8,
and keratin-18 genes have also been described in a series
of 18 children with biliary atresia.36,37 Taken together, the
increased incidence of nonhepatic anomalies in children
with biliary atresia and genetic mutations reported in
subsets of patients with laterality defects suggest that
multiple genes are involved, each affecting a small number
of patients.
Intrahepatic bile ducts are derived from primitive
hepatocytes that form a sleeve (the ductal plate) around
the intrahepatic portal vein branches and associated mes-
enchyme early in gestation. Remodeling of the ductal
plate in fetal life results in the formation of the intrahe-
patic biliary system. This is supported by similarities in
cytokeratin immunostaining between biliary ductules in
biliary atresia and normal first-trimester fetal bile ducts.38
These findings suggest that nonsyndromic biliary atresia
might be caused by a failure of bile duct remodeling at
the hepatic hilum, with persistence of fetal bile ducts
poorly supported by mesenchyme.
Several studies have investigated whether bile duct
epithelial cells are susceptible to an immune/inflammatory
attack because of abnormal expression of human leuko-
cyte antigen (HLA) antigens or intracellular adhesion
molecules on their surfaces.39,40 A greater than threefold
increase in HLA-B12 antigen has been found in babies
with biliary atresia compared with controls, particularly
in those with no associated malformations.41 Aberrant
expression of class II HLA-DR antigens on biliary epi-
thelial cells and damaged hepatocytes in patients with
biliary atresia may render these tissues more susceptible
to immune-mediated damage by cytotoxic T-cells or
locally released cytokines.42 Increased expression of inter-
cellular adhesion molecule-1 (ICAM-1) has been noted
on bile duct epithelium in patients with biliary atresia, a
finding that may play a role in immune-mediated
damage.40 Strong expression of ICAM-1 also has been
found on proliferating bile ductules, endothelial cells,
and hepatocytes in biliary atresia. A direct relationship
exists between the degree of ductal expression of ICAM-1
and disease severity, suggesting that ICAM-1 might be
important in the development of cirrhosis.43
43  Biliary Atresia 581
Interest has also focused on co-stimulatory molecules.
Two processes are involved in the activation of T lym-
phocytes by antigen-presenting cells (APC). One relates
to the expression of major histocompatibility complex
class II molecules, which interact directly with T-cell
receptors. The other depends on the expression of B7
antigens on APC, and provides the second (co-stimulatory)
signal to T-lymphocytes through CD28.44 In postopera-
tive biliary atresia patients with good liver function,
co-stimulatory antigens (B7-1, B7-2, and CD40) are
expressed only on bile duct epithelial cells, whereas in
patients with failing livers these markers are found on the
surfaces of Kupffer cells, dendritic cells, and sinusoidal
endothelial cells and in the cytoplasm of hepatocytes.45
This suggests that the biliary epithelium and hepato-
cytes in biliary atresia are susceptible to immune rec-
ognition and destruction. Agents that block or prevent
co-stimulatory pathways might offer a new therapeutic
approach for reducing liver damage.
Two studies have involved comprehensive molecular
and cellular surveys of liver biopsies and found a proin-
flammatory gene expression signature, with increased
activation of interferon-γ, osteopontin, tumor necrosis
factor-α, and other inflammatory mediators.46,47 These
studies may prove to be helpful in delineating the molec-
ular networks responsible for the proinflammatory
response and autoimmunity thought to be involved in the
pathogenesis of biliary atresia. However, none of these
mechanisms appears to be mutually exclusive. Moreover,
it is not clear which signs and symptoms are primary and
which are secondary.
In summary, the etiology of nonsyndromic biliary
atresia is hypothesized to involve a viral or other toxic
insult to the bile duct epithelium that induces the expres-
sion of new antigens on the surfaces of biliary epithelial
cells.48 Coupled with a genetically predetermined sus-
ceptibility that is mediated via histocompatibility anti-
gens, these neoantigens are recognized by circulating
T-lymphocytes, resulting in an immune cell mediated,
fibrosclerosing response.
CLASSIFICATION
Biliary atresia can be classified by using macroscopic
appearance and cholangiography findings into three main
categories: atresia of the common bile duct (CBD) (type
I), atresia of the common hepatic duct (type IIa) or atresia
of the CBD and the common hepatic duct (type IIb), and
atresia of all extrahepatic bile ducts up to the porta hepatis
(type III) (Fig. 43-1). Most patients have type III. In
patients with a patent CBD and cystic duct (correctable
type) (5% of cases), the gallbladder can be anastomosed
to the porta hepatis, (gallbladder Kasai). In more than
90% of cases, however, no patent extrahepatic ductal
structures are found at the porta hepatis (i.e., ‘noncor-
rectable’ type).49
HISTOPATHOLOGY
Early in the course of biliary atresia, the liver becomes
enlarged, firm, and green. The gallbladder may be small
582 SECTION IV  Abdomen
I IIa
IIb III
FIGURE 43-1  ■  Morphologic classification of biliary atresia based
on macroscopic and cholangiographic findings. Type I, occlu-
sion of common bile duct; type IIa, obliteration of common
hepatic duct; type IIb, obliteration of common bile duct, hepatic
and cystic ducts, with cystic dilatation of ducts at the porta
hepatis, and no gallbladder involvement; type III, obliteration of
common, hepatic, and cystic ducts without anastomosable
ducts at porta hepatis. (From Lefkowitch JH. Biliary atresia. Mayo
Clin Proc 1998;73:90–5.)
FIGURE 43-2  ■  Type III biliary atresia with an enlarged, firm,
green liver and hypoplastic small gallbladder was found in this
infant.
and filled with white mucus, or it may be completely
atretic (Fig. 43-2). Microscopically, the biliary tracts
contain inflammatory and fibrous cells surrounding
miniscule ducts, which are probably remnants of the
original embryonic duct system. The liver parenchyma is
fibrotic and shows signs of cholestasis. Proliferation of
biliary neoductules is seen (Fig. 43-3). This process
develops into end-stage cirrhosis if adequate biliary
drainage cannot be achieved. These early changes are
often nonspecific and may be confused with neonatal
hepatitis and metabolic diseases.
FIGURE 43-3  ■  Photomicrograph of the portal tract of the liver in
a 60-day-old infant with biliary atresia. Ductal plate malforma-
tion can be seen in the center of the portal space with portal
fibrosis. Note ductal metaplasia of hepatocytes (Azan stain,
×100).
It is generally accepted that the pathologic changes
seen in biliary atresia are panductal, affecting the intra-
hepatic biliary tree as well as the extrahepatic bile duct
system. Moreover, the intrahepatic bile ducts can be
narrowed, distorted in configuration, or irregular in
shape.50–52 However, some authors believe that secondary
damage occurs only to the extrahepatic biliary system as
a result of obliteration of extrahepatic bile ducts during
liver formation.53 This theory is strongly supported by
the fact that outcome is better if the portoenterostomy is
performed early.
The intrahepatic biliary tree is important not only
pathologically, but also clinically. The degree of damage
that has already occurred in the intrahepatic biliary
system is actually responsible for much of the morbidity
after hepatic portoenterostomy. Intrahepatic bile duct
proliferation likely results from disturbances in formation
of the ductal plate as well as ductular metaplasia of
hepatocytes.54,55
Certain substances can act as prognostic factors in
biliary atresia. Serum levels of interleukin (IL)-6, IL-1ra,
insulin-like growth factor-1 (IGF-1), vascular cell
adhesion molecule-1 (VCAM-1), and ICAM-1 correlate
with liver dysfunction in postoperative biliary atresia
patients.43,56,57 Immunohistochemically, a reduction in the
expression of CD68 and ICAM-1 at the time of portoen-
terostomy is associated with a better prognosis.58 The
presence of ductal plate malformation in the liver pre-
dicts poor bile flow after hepatoportoenterostomy in
infants with biliary atresia.59 Growth failure and poor
mean weight z-scores three months after hepatoportoen-
terostomy are also associated with a poor clinical
outcome.60
DIAGNOSIS
The cardinal signs and symptoms of biliary atresia are
jaundice, clay-colored stools, and hepatomegaly. However,
meconium staining is normal in most patients. In the
neonatal period, feces are yellow in more than half of

patients.61 The newborn’s urine becomes dark brown.
Although the neonates are active, and their growth is
usually normal for the first few months, anemia, malnu-
trition, and growth retardation develop gradually because
of malabsorption of fat-soluble vitamins. Jaundice that
persists beyond two weeks should no longer be consid-
ered physiologic, particularly if the elevation in bilirubin
is mainly in the direct fraction. Neonatal hepatitis and
interlobular biliary hypoplasia are most likely to be con-
fused with biliary atresia. Conventional liver function
tests alone are useless for establishing a definitive diag-
nosis of biliary atresia.
Although a number of diagnostic protocols have been
published, the emphasis must always be on early diagno-
sis (Box 43-1).62,63 The definitive diagnosis of biliary
atresia requires further investigations, including special
biochemical studies, tests to confirm the patency of the
extrahepatic bile ducts, and needle biopsy of the liver.
Several authors consider liver biopsy to be the most reli-
able test for establishing the diagnosis.64,65 Serum
lipoprotein-X is positive in all patients with biliary atresia,
although it also is positive in 20–40% of patients with
neonatal hepatitis. Serum bile acid levels increase in
infants with cholestatic disease, but both the total bile
acid level and the ratio of chenodeoxycholic acid to cholic
acid have no value for differentiating biliary atresia from
other cholestatic diseases.66 Hyaluronic acid, which has
been considered a serum marker for liver function, has
also been reported to be a biochemical marker for evalu-
ating infants with biliary atresia.67 Duodenal aspiration is
an easy, noninvasive, and rapid test because biliary atresia
can be excluded if bilirubin-stained fluid is aspirated.68
Clinical Findings and Examination
BOX 43-1
for Diagnosis of Biliary Atresia
ROUTINE EXAMINATIONS
Color of stool
Consistency of the liver
Conventional liver function tests, including test for
γ-glutamyl transpeptidase
Coagulation times (PT, aPTT)
SPECIAL EXAMINATIONS
Special biochemical studies
Hepatitis A, B, C serologic studies
TORCH titers
α1-Antitrypsin level
Serum lipoprotein-X
Serum bile acid
Confirmation of patency of extrahepatic bile ducts
Duodenal fluid aspiration
Ultrasonography
Hepatobiliary scintigraphy
Endoscopic retrograde cholangiopancreatography
Near-infrared reflectance spectroscopy
Needle biopsy of the liver for histopathologic studies
Laparoscopy
Surgical cholangiography
aPTT, activated partial thromboplastin time; PT, prothrombin time;
TORCH, toxoplasmosis, other viruses, rubella, cytomegalovirus, and
herpes simplex virus.
43  Biliary Atresia 583
FIGURE 43-4  ■  Ultrasonography shows a well-defined triangular
area of high echogenicity (arrow) at the porta hepatis, corre-
sponding to fibrotic ductal remnants (the ‘triangular cord’ sign).
Hepatobiliary scintigraphy with technetium-labeled
agents is widely used for differentiating biliary atresia
from other cholestatic diseases. In biliary atresia, nucle-
otide uptake by hepatocytes is rapid, but excretion into
the bowel is absent, even on delayed images. In hepato-
cellular jaundice, isotope uptake is delayed owing to
parenchymal disease. Excretion into the intestine may or
may not be seen.
Ultrasonography (US) should be performed on all
jaundiced infants. Hepatobiliary ultrasound will exclude
other surgical causes of jaundice such as choledochal cyst
and inspissated bile syndrome. In biliary atresia, the int-
rahepatic ducts are not dilated on ultrasound because
they are affected by the inflammatory process. Various
sonographic features have been targeted in an attempt to
distinguish biliary atresia from other causes of conjugated
hyperbilirubinemia in infants.69–73 In biliary atresia, the
gallbladder is small, shrunken, and noncontractile, and
there is increased echogenicity of the liver. The presence
of other associated anomalies of the polysplenia syn-
drome is pathognomonic of biliary atresia.74 Differentia-
tion from choledochal cyst and type I biliary atresia also
is rapid and simple with ultrasound.75 Irrespective of
interobserver variation, failure to visualize the CBD is
not diagnostic of biliary atresia because a patent distal
CBD can be found in up to 20% of biliary atresia cases.
However, an absent gallbladder or one with an irregular
outline is suggestive of biliary atresia.73 In some cases, a
well-defined triangular area of high reflectivity is seen at
the porta hepatis, corresponding to fibrotic ductal rem-
nants (the ‘triangular cord’ sign) (Fig. 43-4).70,71
Nonvisualization of the fetal gallbladder may indicate
abnormalities ranging from gallbladder agenesis to biliary
atresia.76 Amniotic fluid digestive enzymes, which are
synthesized by the biliary epithelium, gradually decrease
until 24 weeks of gestation. As it is no longer possible to
differentiate between abnormally low and physiologically
low levels of the enzymes after 24 weeks of gestation, the
prenatal diagnosis of biliary atresia is difficult.77
Most patients with biliary atresia can be correctly
diagnosed by using an appropriate combination of the
584 SECTION IV  Abdomen

A B C

FIGURE 43-5  ■  Salient features of three portoenterostomy procedures are depicted. (A) Modified Kasai portoenterostomy: Interrupted
shallow sutures (thin broken lines) are placed in the liver parenchyma around the transected biliary remnant, except at the 2 and
10 o’clock positions, where the right and left bile ducts should be. If sutures are necessary at the 2 and 10 o’clock positions to
prevent an anastomotic leak, shallow interrupted sutures (thin dotted lines) are placed only in the connective tissue near the right
and left hepatic arteries or the hepatoduodenal ligament at the porta hepatis. (B) Kasai’s original portoenterostomy:23,25 A continuous
suture (looped line) is placed in the side of the transected biliary remnant, except at the 2 and 10 o’clock positions, where sutures
(dotted lines) are placed in the connective tissue. (C) Extended portoenterostomy: Deep interrupted sutures (bold broken lines) are
placed in the liver parenchyma, even at the 2 and 10 o’clock positions. (From Nakamura H, Koga H, Wada M, et al. Reappraising the
portoenterostomy procedure according to sound physiological/anatomic principles enhances postoperative jaundice clearance in biliary
atresia. Pediatr Surg 2012;28:205; and From Yamataka A, Lane GJ, Cazares J. Laparoscopic surgery for biliary atresia and choledochal cyst.
Sem Pediatr Surg 2012;21:201.)

investigations just outlined. However, to accurately dif-

ferentiate biliary atresia, biliary hypoplasia, and severe
neonatal hepatitis, cholangiography is usually required.
Recently, laparoscopy-assisted cholangiography has
been used to display the anatomic structure of the biliary
tree.78 Also, percutaneous cholecystocholangiography
may be a useful option to prevent unnecessary laparot-
omy in infants whose cholestasis is caused by diseases
other than biliary atresia.79

OPERATIVE MANAGEMENT
Open Surgical Technique
Prior to operative exploration, daily doses of vitamin K
should be given for several days, and broad-spectrum
antibiotics are administered preoperatively.
The portoenterostomy procedure for biliary atresia
has been repeatedly modified to achieve better rates of
jaundice clearance and survival, and hardly resembles
Kasai’s original portoenterostomy (Fig. 43-5B). The
current favored technique involves an extended lateral
dissection around the porta hepatis with a very wide
anastomosis (extended portoenterostomy, or EPE)
(Fig. 43-5C).80,81
EPE is the most widely used open approach for treat-
ing biliary atresia. The patient is placed supine on an
operating table with the capability for intraoperative
cholangiography. An extended right subcostal incision,
dividing the muscle layers, is used to expose the inferior
margin of the liver. After division of the falciform and
triangular ligaments, the liver is delivered from the
abdominal cavity. This maneuver provides an excellent
operative field for dissection of the porta hepatis. Cholan-
giography is recommended to identify the anatomy (Fig.
43-6). The fundus of the gallbladder is mobilized from
the liver bed, and a 4–6 French feeding tube is passed
FIGURE 43-6  ■  Intraoperative cholangiogram, type III biliary
atresia. Note the almost atretic common bile duct (arrow).
into the gallbladder through a small cholecystotomy inci-
sion. If bile is detected on aspiration from the gallbladder,
a small amount of contrast material is injected. However,
in most patients with biliary atresia, the lumen of the
atrophic gall bladder is already obstructed, and it is
impossible to insert even a 4 French catheter. Thus,
cholangiography cannot be performed. Unless normal
anatomy of the intrahepatic biliary system can be con-
firmed, hepatic portoenterostomy is performed.24,82
The cystic artery is ligated and divided and the gall-
bladder is dissected from the liver bed. The mobilized
gallbladder is used as a guide for locating the fibrous
remnant of the CBD. After the caudal end of the CBD
is ligated and divided at the upper border of the duode-
num, the cephalad portion of the CBD with the gallblad-
der attached is dissected above the bifurcation of the
portal vein. The portal vein and the hepatic arteries are
exposed along their entire course. For better portal dis-
section, the right and left hepatic arteries and the right
 43  Biliary Atresia 585

and left portal branches are individually encircled with
vessel loops (Fig. 43-7A). The hepatic ducts usually form
a cone-shaped fibrous mass anterior to the bifurcation of
the portal vein. Several small vessels connecting the
portal vein to the fibrous cone are divided after being
ligated. The posterior aspect of the fibrous cone is freed
completely. The anterior aspect of the fibrous cone and
the quadrate lobe of the liver are then exposed. The
fibrous biliary plate should be dissected as far as the
entrance of the anterior branch of the right hepatic artery
on the right side and as far left as the entrance of the
obliterated umbilical vein into the left portal vein. The
fibrous cone is sharply transected at the level of the pos-
terior surface of the portal vein with scissors or a scalpel,
and is removed. The fibrous cone should have an exten-
sive transected surface that allows a wide anastomosis. In
other words, in EPE, dissection of the porta hepatis is
not confined just to the area around the base of the
fibrous ductal plate.83,84 As much of the transected hilar
surface as possible, including all potentially usable rem-
nants of the intrahepatic ducts in the area between and
beneath the branches of the right and left portal veins, is
incorporated in the anastomosis. Also, the right and left
portal veins and hepatic arteries must be retracted to

C
FIGURE 43-7  ■  The current favored technique for a portoenterostomy involves an extended lateral dissection around the porta hepatis
with a very wide anastomosis. (A) Photograph of the initial mobilization of the gallbladder and atretic bile ducts and dissection/
exposure of the porta hepatis. After the common bile duct remnants are severed from the duodenal side, the dissection proceeds
cephalad and the portal bile duct remnants are freed from the underlying structures. The portal vein and hepatic artery have been
encircled with vessel loops. Several small vessel branches between the portal vein to the fibrous remnant can be identified and
divided between ligatures. (B) The portal bile duct remnants must be dissected 5 or 6 mm proximal to the anterior branch of the
right hepatic artery on the right side and as far left as the entrance of the obliterated umbilical vein into the left portal vein. The
fibrous cone is sharply transected at the level of the posterior surface with scissors or a scalpel, and is removed. The fibrous cone
should have an extensive transected surface, which allows a wide anastomosis. (C) The end of the Roux-en-Y limb is anastamosed
around the transected end of the fibrous remnant. Sutures should not be placed into the transected surface of the bile duct remnant,
because minute bile ducts may be present. As much of the transected hilar surface as possible, including all potentially usable
remnants of the intrahepatic ducts in the area between and beneath the branches of the right and left portal veins, is incorporated
in the anastomosis. It is important to retract the right and left portal veins and hepatic arteries to allow extensive reception of the
biliary remnant and a wide portoenterostomy.
586 SECTION IV  Abdomen
allow extensive resection of the biliary remnant and a
wide portoenterostomy.
During the dissection, 5-0 or 6-0 absorbable mono-
filament sutures are usually placed in the liver surface
posterior and caudal to the fibrous plate before transect-
ing it (Fig. 43-7B). It is important to have adequate dis-
tance between these sutures and the remnant fibrous
plate because it will be difficult to transect the fibrous
plate if the sutures are too close to it. Bleeding points are
controlled by packing with gauze. Diathermy should not
be used as it can cause damage to any microscopic patent
bile ducts. A liver biopsy should be performed on the
right lobe to obtain histopathologic data for prognostic
purposes. Also, if intraoperative histology of the transected
portal fibrous plate does not identify microscopic (110–
150 µm) patent bile duct structures at the transected
surface, further cephalad dissection and transection of the
portal fibrous plate is needed.85–87
A Roux loop of 30–40 cm is prepared by dividing the
jejunum approximately 15 cm downstream from the liga-
ment of Treitz. The distal end may be oversewn or left
open, and is passed in a retrocolic position to the hepatic
hilum. Small bowel continuity is re-established with an
end-to-side enteroenterostomy. The hepatic portoenter-
ostomy is performed in an end-to-side or end-to-end
fashion using interrupted 5-0 or 6-0 sutures. Using the 5-0
or 6-0 sutures that were previously placed posterior to the
fibrous plate, the posterior aspect of the portoenterostomy
is performed first (Fig. 44-7C). Next, the anterior edge of
the jejunum is anastomosed to the liver parenchyma ante-
rior to the transected fibrous hilar remnant with inter-
rupted 5-0 or 6-0 monofilament absorbable sutures,
including the 2 and 10 o’clock positions. There should be
adequate space between the anterior margin and the
remnant fibrous plate as well. A small drain is positioned
in the foramen of Winslow through a separate stab inci-
sion in the right abdominal wall and the incision is closed.
Modified Kasai Original
Portoenterostomy
In contrast to the EPE technique just described, in both
Kasai’s original portoenterostomy (KOPE) and our pre-
ferred modified KOPE (M-KOPE), dissection of the
porta hepatis is confined to the area around the base of
the fibrous biliary plate which is not transected very
deep.27,88,89 As a result, the portoenterostomy anastomosis
is not as wide as in the EPE technique. We place inter-
rupted sutures in the liver parenchyma around the outer
edge of the transected biliary remnant except at the 2 and
10 o’clock positions. At the 2 and 10 o’clock positions,
where the right and left hepatic ducts should be, sutures
are placed very shallow in the connective tissue near the
right and left hepatic arteries or the hepatoduodenal liga-
ment at the porta hepatis, and not to the side of the
transected biliary remnant.27,89 These sutures are placed
shallow, especially at the 2 and 10 o’clock positions, to
minimize microscopic bile duct injury, but deep enough
to prevent leakage at the portoenterostomy. See Figure
43-5 for a comparison of M-KOPE (Fig. 43-5A), KOPE
(Fig. 43-5B), and EPE (Fig. 43-5C).
Hepaticojejunostomy
Kimura reported that in correctable biliary atresia,
although a wide and deep portal dissection is not required,
excision of the patent CBD cephalad to the liver
hilum is important.90 Any cyst-like structure should be
excised and should not be used for anastomosis to the
intestine. Failure to remove all abnormal CBD or hepatic
duct tissue may result in anastomotic stricture or
cholangitis.
Nio reported on 323 biliary atresia patients undergo-
ing operation between 1953 and 2004.91 Fifty patients
were classified as type I. In these 50 patients, 28 under-
went portoenterostomy and 22 underwent hepaticoen-
terostomy. The overall survival rate for type I patients
who did not require liver transplantation was significantly
better than type II/III patients (52% vs 33%). However,
the authors also found a higher incidence of cholangitis
in type I patients, but this difference was not statistically
significant.
Recently, in a review of 200 patients from 1963–2008
at one institution, the authors reported excellent long-
term outcomes in 12 patients who had a hilar cyst and
underwent hepaticojejunostomy (type I cyst: 9 cases and
a subtype of type II: 3 cases).92 The overall survival with
the patient’s native liver was 83.3%.
Minimally Invasive Kasai Operation
The first laparoscopic Kasai (lap-Kasai) procedure was
described in 2002.93 Since that report, there have been
few others performed, probably because the procedure
itself is technically complicated. Moreover, it may be
associated with an increased incidence of postoperative
complications and a worse early clinical outcome.94 It has
been suggested that the pneumoperitoneum compro-
mises liver perfusion with subsequent liver cell damage.95
In a rat model, it was shown that elevated intra-abdominal
pressure can decrease hepatocyte proliferation and induce
liver cell apoptosis.96 One report found there was no
measurable benefit of laparoscopy compared with open
portoenterostomy regarding the amount of scarring and
adhesions at the time of liver transplantation.97 On the
other hand, one recent study found relatively good out-
comes at a median follow-up of 72 months (range: 33–89
months) after lap-Kasai, with 50% (eight cases) of the
patients being jaundice-free with normal bilirubin levels.98
Also, recently, a prospective study compared lap-Kasai
to conventional Kasai and found that lap-Kasai was
technically feasible.99 However, the study also found
worse survival after 24 months in the 12 infants who had
lap-Kasai compared with infants who had conventional
surgery.
The authors began performing the M-KOPE via
laparoscopy in 2009.100 During lap-Kasai, the Ligasure is
used to divide portal vein branches draining into the
caudate lobe at the porta hepatis. The Ligasure generates
much less heat laterally when compared to monopolar
hook diathermy that can cause thermal injury to the
microscopic bile ductules in the fibrous plate during dis-
section.101,102 The Roux limb is created by exteriorizing
the jejunum through the umbilical port. The length of

FIGURE 43-8  ■  The length of the Roux-en-Y (RY) limb
is determined by exteriorizing the jejunal loop
through the umbilicus and measuring the distal end
(E) of the limb to be 3 cm above the xiphoid process.
The jejunojejunostomy (arrowheads) will then fit
naturally into the splenic flexure after anastomosis.
Arrows show where the RY limb has been approxi-
mated to the native jejunum for 8 cm cranially to
streamline flow into the distal jejunum and elimi-
nate reflux into and stasis in the RY limb. (From
Yamataka A, Lane GJ, Cazares J. Laparoscopic surgery
for biliary atresia and choledochal cyst. Sem Pediatr
A B
Surg 2012;21:201.)
the Roux limb is customized by measuring it to reach just
above the xiphoid process (Fig. 43-8). The Roux limb
tends to be shorter than with the open approach. The
jejuno-jejunostomy is performed extracorporeally. The
portoenterostomy is then performed as described using
the M-KOPE technique.
Repeated Hepatic Portoenterostomy
Bile drainage after reoperation is significant only in
patients with good bile excretion after the initial
surgery.103,104 As liver transplantation is a good option,
repeated hepatic portoenterostomy should only be con-
sidered for selected patients in whom good bile flow
suddenly ceases, or in those patients who might benefit
from a delay in transplantation.105
POSTOPERATIVE MANAGEMENT
Most centers have standardized protocols for postopera-
tive corticosteroid, antibiotic, and choleretic usage. Cor-
ticosteroids are used routinely both for their choleretic
effect and to decrease scarring at the anastomosis site.106,107
Ursodeoxycholic acid may be useful in augmenting bile
flow, but only in the presence of patent bile ductules.
Fat-soluble vitamins (A, D, E, and K) and formula feeding
enriched with medium-chain triglycerides are also used.
The authors’ postoperative management protocol
includes decreasing the dose of intravenous prednisolone
once the C-reactive protein level falls below 1.0 mg/dL.88
Each dose is given for three days, commencing with an
initial dose of 4 mg/kg/day, then 3, 2, 1 mg/kg/day, and
finishing with 0.5 mg/kg/day. This 15 day cycle can be
repeated up to four to five times if jaundice persists (total
bilirubin >1.2 mg/dL) and if there is evidence of clinical
benefit (ie, lower serum bilirubin or improvement in stool
color). However, if jaundice persists without clinical
improvement, then only three cycles are administered and
the patient is considered for liver transplantation. Also, if
stools begin to turn pale, the cycle is either restarted from
the beginning, or the previous dose is re-administered.
Double agent antibiotic therapy, usually a cephalosporin
and an aminoglycoside, is routine and stopped once the
C-reactive protein is less than 0.3 mg/dL. An intravenous
43  Biliary Atresia 587
cholagog (usually dehydrocholic acid) is begun on day 2
after portoenterostomy and continued until jaundice
clears. Oral choleretics such as ursodeoxycholic acid or
aminoethylsulfonic acid are administered once oral
feeding is started and continued thereafter.
COMPLICATIONS
Cholangitis
Cholangitis, defined as an elevated serum bilirubin
(7.5 mg/dL), leukocytosis, and normal to acholic stools
in a febrile patient (>38.5°C), is the most frequent com-
plication occurring after portoenterostomy, and most
commonly occurs during the first 2 years. Cholestasis is
the main risk factor because all patients with biliary
atresia have very small ducts and all conduits become
colonized within a month of operation.
Approximately 40% of infants develop cholangitis.
Patients present initially with fever, decreased quantity
and quality of bile excretion, elevation in serum bilirubin,
and signs of infection. Prompt treatment is necessary
because recurring attacks cause progressive liver damage.
After initial blood cultures, broad-spectrum antibiotics
with good Gram-negative coverage are started, and a
favorable response usually results. If stools become
acholic, a pulse of corticosteroids is given. To decrease
the risk for cholangitis, Roux-en-Y biliary reconstruction
has been modified by various maneuvers, including
lengthening the Roux-en-Y limb from 50 cm to 70 cm,
total diversion of the biliary conduit, creation of an intes-
tinal valve, and the use of a physiologic intestinal valve.108–
112
The antireflux intussusception valve may be the best
modification, and may result in a reduced rate of cholan-
gitis. A gallbladder conduit is not recommended when
the lumen of the patent duct is narrow or when pancrea-
ticobiliary anomalies are demonstrated on cholangiogra-
phy. Stomas complicate liver transplantation, which may
be required later.
Cessation of Bile Flow
Loss of bile pigment in the stool in a patient with an
apparent well-functioning portoenterostomy is an
588 SECTION IV  Abdomen
* cation of chronic liver disease in children with biliary
FIGURE 43-9  ■  CT scan of a 20-year-old woman in whom severe
portal hypertension developed. Note marked atrophy of the left
lobe of the liver, severe splenomegaly, and varices (asterisk)
around the stomach.
ominous sign, and parents should be encouraged to report
changes in stool color or signs of cholangitis immediately.
Prompt re-establishment of bile flow is imperative to
avoid liver damage. If bile flow ceases, a corticosteroid
pulse is given as corticosteroids both augment bile flow
and reduce inflammation.106,107 If bile flow is re-established,
then the corticosteroid dose is reduced. If bile flow is not
re-established, the corticosteroids are stopped. If bile flow
was initially good, it is reasonable to consider reoperation
in selected cases. However, multiple attempts at reopera-
tion generally increase the technical difficulty of subse-
quent transplantation.
Portal Hypertension
Portal hypertension is common after portoenterostomy,
even in infants with good bile flow. The basic inflamma-
tory process affecting the extrahepatic ducts also damages
the intrahepatic branches. Persistent hepatic fibrosis has
been found in some children despite successful portoen-
terostomy.113 Clinical manifestations of portal hyperten-
sion include esophageal varices, hypersplenism, and
ascites (Fig. 43-9). Over time, the susceptibility to com-
plications from portal hypertension seems to decrease,
resulting in reduced frequency and severity of variceal
bleeding. This observation is difficult to explain and may
be related to improvement in hepatic histology or
the development of spontaneous portosystemic shunts.
This observation justifies a nonsurgical approach to the
portal hypertension as long as hepatic function is pre-
served (i.e., the patient remains anicteric with no coagu-
lopathy and normal serum albumin level). However, in
the presence of poor hepatic function, complications
from portal hypertension are an indication for liver
transplantation.
Intrahepatic Cysts
Biliary cysts, or ‘lakes,’ can develop within the livers of
long-term survivors, and cause recurring attacks of
cholangitis (Fig. 43-10).114 Prolonged antibiotics and
ursodeoxycholic acid may be helpful in preventing
cholangitis, but unremitting infection is an indication for
liver transplantation.
Hepatopulmonary Syndrome
Diffuse intrapulmonary shunting can occur as a compli-
atresia. This shunting is likely a result of vasoactive com-
pounds from the mesenteric circulation that are not deac-
tivated in the liver. This syndrome is characterized by
cyanosis, dyspnea on exertion, hypoxia, and finger club-
bing. It appears to be more prevalent in children with
syndromic biliary atresia. The diagnosis is confirmed by
using a combination of arterial blood gas analysis with
and without inspired oxygen, radionuclide lung scans
with macroaggregated albumin to quantify the degree of
shunting, and contrast bubble echocardiography. This
complication is progressive and can usually be reversed
by liver transplantation. Pulmonary hypertension is an
uncommon complication, but can also develop in long-
term survivors after portoenterostomy.
Hepatic Malignancy
Rarely, malignant changes (hepatocellular carcinoma or
cholangiocarcinoma) complicate long- standing biliary
cirrhosis after portoenterostomy. A case of hepatocellular
carcinoma has been reported in a 19-year-old post-Kasai
male biliary atresia patient, indicating the need for a high
index of suspicion for the development of carcinoma,
even in young patients.115
Other Complications
Due to the presence of residual hepatic disease, metabolic
problems associated with malabsorption of fat, protein,
vitamins, and trace minerals can occur postoperatively
because of impairment of bile flow to the gut.116,117
Weight gain after portoenterostomy may be retarded if
hepatic dysfunction persists. Essential fatty acid deficien-
cies and rickets are common problems related to meta-
bolic derangements.118 Long-term monitoring of clinical
FIGURE 43-10  ■  CT scan of a 17-year-old with biliary atresia.
Multiple biliary cysts or ‘lakes’ have developed within the liver
of this long-term survivor and caused recurrent attacks of
cholangitis.

symptoms and adequate nutritional supplementation are
needed. Ectopic intestinal variceal bleeding and pulmo-
nary arteriovenous fistulas are sometimes seen in long-
term survivors with incomplete relief of impaired liver
function.119,120
As more postoperative biliary atresia patients are now
reaching adulthood, the issue of pregnancy in females is
becoming more common. In nontransplanted corrected
biliary atresia patients, preterm cesarean delivery at
around the 34th week appears to be reasonable because
this is a high risk pregnancy in a patient with poor hepatic
reserve. Conversely, delivery at full term may be possible
for selected mothers with good liver function.121
RESULTS AND PROGNOSIS
Without question, the Kasai hepatic portoenterostomy
has greatly improved outcomes of infants with biliary
atresia, and the results of surgical treatment have
improved steadily over the past 30 years. Classically, the
major determinants of satisfactory outcome after por-
toenterostomy are (1) age at initial operation; (2) success-
ful achievement of postoperative bile flow; (3) presence
of microscopic ductal structures at the hilum; (4) the
degree of parenchymal disease at diagnosis; and (5) tech-
nical factors at the anastomosis. Age at portoenterostomy
is the single most widely quoted prognostic variable. A
favorable outcome is expected if the procedure is per-
formed before 60 days of age, because cirrhosis will
develop by 3 to 4 months of age. However, a wide dis-
crepancy exists in reported long-term results. One study
from Japan found postoperative outcome to be excellent,
with a ten-year survival rate of more than 70%, if the
portoenterostomy was performed before 60 days of age.122
However, a nationwide survey of the Surgical Section of
the American Academy of Pediatrics found that long-
term survival was only 25%.26 Other reported 10-year
survival rates include 40–50% from the UK and 68%
from France.1,123 Outcomes are considerably worse if the
infant is older than 100 days at the time of portoenteros-
tomy because obliterative cholangiopathy and hepatic
fibrosis have already developed.123,124
The impact of age at portoenterostomy on long-term
outcome, especially in patients with type III biliary
atresia, was recently evaluated.125 Age at portoenteros-
tomy was found to have a significant impact on jaundice
clearance, but not on long-term survival in type III biliary
atresia, suggesting that age at portoenterostomy might be
less significant as a prognostic factor over time. In another
study from Hong Kong, portoenterostomies performed
beyond the age of 60 days was not associated with worse
outcome, and a high percentage of patients could still
achieve good bile flow and a normal bilirubin postopera-
tively.126 Of particular interest is a report by Kuroda et al,
who reviewed postoperative biliary atresia patients in
relation to pregnancy and found that age at portoenter-
ostomy may not necessarily influence long-term
outcome.127 However, liver function at puberty may be a
useful indicator and may be predictive for the safety of
pregnancy. Also, management strategies may need to be
revised accordingly after puberty.
43  Biliary Atresia 589
The presence of microscopic ducts at the hilum is
somewhat controversial.128,129 Some authors have sug-
gested that duct size is important, but there is not uni-
versal agreement. Types I and II biliary atresia generally
have a good prognosis if treated early. In the more typical
type III disease, the presence of larger bile ductules at the
porta hepatis (>150 µm in diameter) is associated with a
better prognosis. The subgroup of infants with syndro-
mic biliary atresia have worse outcomes in terms of both
clearance of jaundice and survival.1,28 The latter is related
to associated malformations (particularly congenital heart
disease), a predisposition to developing hepatopulmonary
syndrome, and possible immune compromise from func-
tional hyposplenism. Personal experience suggests that
infants with concomitant CMV infection fare less well
after a portoenterostomy.
The importance of surgeon experience was shown in
a British survey in which patients who underwent por-
toenterostomy at centers treating one case per year had
significantly worse outcomes than patients who were
treated at centers performing more than five cases per
year.130 Since 1999, the management of biliary atresia has
been centralized to three centers in England and Wales
that are able to offer both portoenterostomy and trans-
plantation. In 2011, the results of this policy change were
reported, and it was found that outcomes were better
than previously reported.131 These improved outcomes
may be due to centralization of surgical and medical
resources.
Recently, outcomes in infants enrolled in the prospec-
tive Childhood Liver Disease Research and Education
Network who underwent portoenterostomy were
reported. Liver anatomy, splenic malformation, presence
of ascites, liver nodularity at portoenterostomy, and early
postoperative clearance of jaundice were found to be sig-
nificant predictors of transplant-free survival.132
Irrespective of age and other factors related to the
timing of portoenterostomy, a significant decrease in
serum bilirubin and signs of good bile excretion in the
stool may be predictive of good long-term outcome.133
Due to the possibility of sudden hepatic deterioration
and the constant concern for cholangitis and portal
hypertension, recent reports about long-term outcomes
in biliary atresia patients consistently emphasize lifelong
follow-up.134,135
LIVER TRANSPLANTATION
The indications for liver transplantation following
portoenterostomy are: (1) lack of bile drainage; (2) signs
of developmental retardation or their sequelae; and
(3) complications/side effects being socially unacceptable.
A high hepatic artery resistance index measured on
Doppler ultrasound is an indication for relatively urgent
transplantation.136 Deterioration in hepatic status may be
precipitated by adolescence or pregnancy. However, as
many as 20% of patients undergoing portoenterostomy
will remain healthy and reach adulthood with good liver
function.
The dramatic improvement in survival with the use of
cyclosporine and tacrolimus immunosuppression after
590 SECTION IV  Abdomen
liver transplantation raises the question of transplanta-
tion becoming a more conventional form of treatment
for biliary atresia. The donor supply is always a problem,
alleviated to some extent by reduced-size liver transplan-
tation. Five-year survival after liver transplantation for
biliary atresia is currently 80–90%, and techniques such
as split-liver grafting and living-related liver transplanta-
tion have decreased waiting times.137 Furthermore, long-
term studies of post-transplant biliary atresia patients
have shown that survivors have an acceptable to good
quality of life.138,139
A recent study summarized the largest series (n = 464)
of postportoenterostomy patients who had undergone
living-related liver transplantation.140 The outcome of
living-related liver transplantation in adults with biliary
atresia was significantly worse than in infants and chil-
dren. The overall five- and ten-year survival rates were
70% and 56% in adults versus 87% and 81% in pediatric
patients, respectively. On the other hand, there is a report
concluding that living-related liver transplantation after
portoenterostomy can be performed safely in adults with
a long-term survival rate equivalent to that for pediatric
patients.141 Longer immunosuppression might ultimately
lead to increased morbidity, including higher rates of
cancer, infection, and metabolic diseases later in life. In
addition, in living-related liver transplantation, the risk
to the donor is always a concern.142 The optimal timing
of transplantation in postportoenterostomy patients has
yet to be established.
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