This document summarizes the outcome and management of biliary atresia. It discusses the Kasai portoenterostomy procedure, which aims to restore bile flow in infants with biliary atresia. About 50% of infants will clear their jaundice following this surgery. Long-term outcomes depend on factors like degree of cirrhosis and the experience of the surgeon. Complications include cholangitis in 30-60% of cases within the first year, and portal hypertension in many infants initially but depending on the liver response to surgery.

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Symposium on Hepatology and Gastroenterology
Biliary Atresia: Outcome and Management
Mark Davenport
Department of Pediatric Surgery, King’s College Hospital, London SE5 9RS
ABSTRACT
Untreated, biliary atresia remains a fatal condition of the newborn. Most present within four to six weeks of conjugated jaundice
and acholic stools, and, although still a challenging diagnosis to make, therein lies the opportunity of changing the course of
this otherwise inexorable disease. The aim of surgery is to restore bile flow, alleviate jaundice and abbreviate the
cholangiodestructive process within the liver. The Kasai portoenterostomy, introduced almost 50 years ago in Japan, aims to
expose microscopic biliary ductules within the fibroinflammatory mass at the porta hepatis, and restore bile drainage into a
mobilised Roux loop. About 50% of infants with BA will be able to clear their jaundice following Kasai alone, given appropriately
experienced surgeons and if performed prior to the onset of overt cirrhosis. They have a reasonable expectation of long-term
survival to adulthood with a good quality-of-life. The remainder may be candidates for liver transplantation (where available)
although donor organ shortage and immunosuppresion-related complications remain significant problems. [Indian J Pediatr
2006; 73 (9) : 825-828] Markdav2@ntlworld.com; Mark.Davenport@kingsch.nhs.uk
Key words : Biliary atresia; Kasai portoenterostomy
Biliary atresia (BA) is a cholangiodestructive disease of
both intra- and extrahepatic parts of the biliary system
which leads to cirrhosis and ultimately liver failure and
remains the commonest indication for pediatric liver
transplantation throughout the Western world.
The incidence of BA is higher in Japan, China and
probably south Asia (~1 in 8-9 000)than in Europe and the
USA (~ 1 in 12 - 15 000 live births). 1,2
In the latter
countries about 10% of cases have other congenital
abnormalities, and specifically a syndromic association
which we have termed the Biliary Atresia Splenic
Malformation (BASM) syndrome.3
This is characterised as
having splenic pathology (usually polysplenia), situs
inversus, cardiac and vascular anomalies such as an
absence of the inferior vena cava and a pre-duodenal
portal vein. There is a marked female predominance and
a first-trimester illness or insult (e.g. maternal diabetes)
may be causative in this sub-group.
PATHOLOGY
The macroscopic appearance of the extrahepatic biliary
tree ranges from an inflamed, hypertrophic occluded
biliary tract to an atrophic negligible remnant with absent
Correspondence and Reprint requests : Dr. M. Davenport,
Department of Pediatric Surgery, King’s College Hospital, Denmark
Hill, London SE5 9RS, Tel.: 0044 (0) 207 346 3350; Fax : 0044 (0) 207
346 4021.
Indian Journal of Pediatrics, Volume 73—September, 2006
parts. The histological appearance of the liver is
characterised by portal tract inflammation, a small cell
infiltrate, bile ductule plugging and proliferation and in
the later stages bridging fibrosis giving way to features of
overt biliary cirrhosis. The lumen of the extrahepatic duct
is obliterated at a variable level and this forms the basis
for the commonest classification in clinical use (Table 1).
The other main macroscopic variation is that of cystic
change, seen in about 5% of cases, within some part of the
extrahepatic biliary tree.4
Some cysts contain mucus,
while others contain bile. If it is the latter there may be
some diagnostic confusion with that of a true choledochal
cyst. However, in cystic biliary atresia, the wall is
invariably thickened and communicates poorly with
abnormal non-dilated intrahepatic ducts. This should be
obvious on a cholangiogram (operative, percutaneous or
ERCP).
CLINICAL FEATURES
All infants with biliary atresia will be jaundiced and have
pale stools and dark urine. Some infants will have had an
abnormal antenatal ultrasound scan (~ 5%), because of the
cystic change in the biliary tree or may present because of
the other congenital abnormalities.4
Clinical features of
cirrhosis, such as ascites and marked hepato­
splenomegaly, are uncommon before 70-80 days of age. A
small proportion of infants will present with features of a
Vitamin K-dependent coagulopathy (e.g. umbilical stump
bleeding, melena or intracerebral bleeding) bleeding,
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Mark Davenport
particularly in those communities where routine neonatal
administration of parenteral Vitamin K is not practiced.
The differential diagnosis of infants with conjugated
jaundice is long and outside of the scope of this article.
Some common medical causes include neonatal hepatitis,
á1-antitrypsin deficiency, giant cell hepatitis,
cytomegalovirus hepatitis, Alagille’s syndrome, and
cystic fibrosis. There are other less common surgical
causes including obstructed choledochal malformations,
spontaneous perforation of the bile duct and the
inspissated bile syndrome.5
Pertinent investigations include ultrasonography, liver
biochemistry, viral serology, and ideally a percutaneous
liver biopsy. In some centres, duodenal intubation and
measurement of intralumenal bile is practised as the
routine test for BA. Newer modalities such as ERCP and
MRCP have been used at times, although the former is
clearly highly operator-dependent and the latter not
sufficiently precise in its delineation of infantile biliary
anatomy to offer real advantage.6
In a number of centres,
operative cholangiography remains the key investigation
in demonstrating biliary patency. Occasionally this may
be performed laparoscopically with good results.7
The surgical strategy for BA has evolved over the past
20 years incorporating liver transplantation (where
available) as a complementary technique to the older
Kasai portoenterostomy. In some cases (typically with
established cirrhosis and ascites), a case may be made for
primary liver transplantation but this should be an
unusual occurrence if the infant presents at less than 100
days.
KASAI PORTOENTEROSTOMY
The aim of the procedure is to excise all visible
extrahepatic biliary remnants allowing a wide
portoenterostomy onto a denuded portal plate. In most
cases, this will expose sufficient transected microscopic
bile ductules which retain connections with the primitive
intrahepatic bile ductule system to allow restoration of at
least some worthwhile biliary drainage. This is clearly the
object in type 3 biliary atresia, but should also be strongly
considered even in those who have a visible bile­
containing bile duct (types 1 and 2).
There are many differences in the detail of this
operation and this coupled with its infrequency amongst
pediatric surgeons may explain the wide variations seen
in reported results. We believe that the liver should be
mobilised fully outside of the abdominal cavity (by
division of its suspensory ligaments), to ensure maximal
exposure of the porta hepatis and a detailed dissection.8
The portal dissection itself must be wide extending from
exposure of the origin of the umbilical vein from the left
portal vein in the Rex fossa and encompassing the often
bifurcating right portal pedicle. Small veins from the
portal vein to the portal remnant should also be divided
to expose the caudate lobe posteriorly. Most transected
ductules are found in the marginal areas, recapitulating
the normal biliary arrangement, and it is important to
allow these to drain into a long (~40 cms) Roux loop.
Modifications such as an intussusception valve, stomas or
implanting the distal end of the Roux into the duodenum
have no real advantages in clinical practice and have been
discontinued in most centres.
Some centres have reported the Kasai operation as a
laparoscopic or at least laparoscopic-assisted procedure.
Given that the only real measure of success in the Kasai is
clearance of jaundice it is difficult to believe that this
offers anything more in the necessarily, detailed
procedure of hilar dissection – the key to its success.
Cosmetic advantages are only temporary if the end result
is a transplanted liver.
There are a number of drugs which have been
suggested to improve post-operative results. For
instance, there are anecdotal and uncontrolled studies
suggesting benefit from corticosteroids 9,10
,
ursodeoxycholic acid10
and even Chinese herbs11
.
However, none have been subjected to anything like
acceptable scientific scrutiny. Early results from our own
institution on a randomised double-blind, placebo­
controlled trial using post-operative prednisolone (2mg/
kg/day) did not show any significant clinical difference.
PROGNOSTIC FACTORS AND COMPLICATIONS OF
THE KASAI
There are many factors, which will influence surgical
outcome. Some are unalterable (e.g. degree of cirrhosis or
fibrosis at presentation; absence of, or paucity of,
microscopic bile ductules at the level of section) and some
are subject to change (e.g. surgical experience, untreated
cholangitis). In large studies from the UK and France,
children with BASM do less well in comparison to non­
syndromic infants.12,13
Reasons for increased mortality in
this group are the associated malformations particularly
severe congenital cardiac disease and hepatopulmonary
syndrome.14,15
The age of the infant has an effect on outcome
although this is not as clear-cut as was once thought.
There is no real cut-off (e.g. six or eight weeks); these were
simply the arbitrary values from earlier small-scale
studies. There is no doubt that the fibrotic element of the
hepatopathology is progressive but beyond what age an
attempt at a Kasai portoenterostomy is pointless is not
known. Some infants will come to surgery early with
very soft, non-fibrotic livers, at 20 days for instance, but
because there are few residual ductules in the porta
hepatis their Kasai’s will fail. In contrast, our own series
did show jaundice-free survival in infants (admittedly a
lower proportion) coming to surgery beyond 100 days.16
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Biliary Atresia : Outcome and Management
OUTCOME OF SURGERY FOR BILIARY ATRESIA -
RECENT RESULTS
An excellent outcome following portoenterostomy can be
characterised as clearance of jaundice (to normal levels),
abbreviation of hepatic fibrosis (i.e. absence of clinical
portal hypertension) and avoidance of ascending
cholangitis. Just how many actually achieve this is
fiercely debated. There are two criteria which should be
looked for in any report: clearance of jaundice (to a
defined level) and the proportion that retain their own
liver. The former crystallises the desired effect of the Kasai
in reversing cholestasis (and is also highly predictive of
ultimate outcome), the later is unequivocal and may be
used to compare results from disparate centres.
Table 2 illustrates published outcome from around the
world.1, 12, 13, 15, 17-19
There is clearly the risk of publication
bias in single centre reports – no one wants to publish
poor results. With this in mind, probably the most
reliable reports are from the national outcome studies of
England and France 2, 12,13
which are probably
representative of the European experience, and that of the
Biliary Atresia Registry from Japan.1
In our own recent
study based on experience in England and Wales, the
clearance of jaundice rate was 57% with a 4-year
estimated native liver survival of 51%.
Long-term results (i.e. 10 years or greater) are less
readily available as Kasai’s operation was not readily
performed or even available to vast numbers of infants
born in the 1970s and early 1980s. Nevertheless our own
figures would suggest that about 45% will reach their
teenage years with their own livers,15
and up to 15% will
have a truly long-term, symptom-free, hospital-free,
normal liver biochemistry existence.20
Nevertheless even
in these children apparently “cured” of their biliary
atresia, liver histology when looked at is still very
abnormal.21
The prospect of native liver survival to
adulthood is therefore probably only available to a
minority and a successful liver transplant procedure at
some later point in life should probably be a realistic aim
for most infants now born with biliary atresia.
Aside from end-stage liver disease (i.e. increasing
jaundice, ascites, failure to thrive etc.), there are two main
complications which may follow a Kasai and to some
extent are treatable. These are cholangitis and portal
hypertension. Cholangitis occurs most commonly in the
year following primary surgery in about 30 - 60% of
children. Paradoxically, it only occurs in children with
some degree of bile flow. Infants who have had no effect
from a Kasai do not suffer from cholangitis, principally
because no connections have been established between
the residual intrabiliary bile ducts and the Roux loop.
Clinically, cholangitis is characterised by worsening
jaundice, fever and acholic stools. The diagnosis may be
confirmed by blood culture or by percutaneous liver
TABLE 1. Classification of Biliary Atresia (derived from Japanese Association of Pediatric Surgeons)
Definition
Type 1 (~5%) Level of obstruction is within the common bile duct.
Gallbladder contains bile.
Type 2 (~ 3%) Level is within the common hepatic duct.
The gallbladder will not contain bile but a transection of the
proximal remnant should show two distinct bile-containing lumens.
Type 3 (>90%) Obstruction is within the porta hepatis.
No visible bile-containing proximal lumen.
TABLE 2. Recent Results in Biliary Atresia
Series & country Period N Clearance jaundice Native liver survival Notes
5 yr 10 yr
Hung et al. (Taiwan)17
1976 - 2000 141 61% 35% 31% Single centre
Davenport et al. (UK)12
1999 - 2002 148 57%* 51%* n/a UK national study
Chardot et al. (France)13
1986 - 1996 472 n/a 52% 27% French national study
Altman et al. (USA)18
1972 - 1996 266 n/a 45% 35% Two-centre study from advent
of Kasai operation in USA
Nio et al. (Japan)1
1989 - 1994 735 57%** 52 – 64%** 53% Japanese national study
Davenport et al. (UK)15
1973 - 1995 338 n/a 50 - 60%*** 41% Single centre study from
advent of Kasai operation
in UK
Karrer et al. (Denver)20
1973 - 1985 98 n/a n/a 24% Single centre study from
advent of Kasai operation
in USA
* < 20 mol/L and 4 year native liver survival
** < 2 mg/% (=34 µmol/L) and by year cohort
*** by year cohort
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Mark Davenport
biopsy, but it is important to realise that actual
microbiological confirmation in uncommon and early
empirical treatment with broad-spectrum antibiotics
effective against gram-negative organisms is indicated.
Recalcitrant cholangitis can be a problem in some children
and be associated with parenchymal cyst formation, too
short a Roux loop or problems with loop drainage.
Radioisotope scans may uncover a dysfunctional Roux
loop and lead to surgical revision or internal diversion of
a large cystic space. Alternatively, long-term antibiotic
therapy should overcome the tendency to recurrent
sepsis.
Portal hypertension has been shown in virtually all
infants at the time of the Kasai operation. However
subsequent portal hypertension depends both on the
degree of established fibrosis and, most importantly, the
response to surgery. In those who fail and need early
transplantation about 30% will have had a significant
variceal bleed. In those who respond well to initial Kasai,
but who have established fibrosis then variceal
development can be delayed and presentation with
bleeding perhaps only occurs at 2-3 years. The
emergency treatment of bleeding varices is a combination
of blood transfusion, correction of thrombocytopenia, and
coagulopathy together with acute endoscopy to confirm
the diagnosis and initiate treatment. Specific agents to
lower portal pressure (e.g. the somatostatin analogue,
octreotide) may also be useful where available. A
sengstaken tube may occasionally be required when there
is on-going bleeding to enable a clear enough view for
definitive endoscopic therapy. Although injection
sclerotherapy (e.g. ethanolamine) retains a role in treating
varices in infants, most older children are better suited to
endoscopic variceal banding.21
In children with
reasonable restoration of liver function and particular
those that are jaundice-free prior to the bleeding episode
then endoscopic control may be the only therapy
necessary. However, where varices are symptomatic of a
failing liver then transplantation is the only realistic
procedure with a long-term chance of success.
Currently, in large centres with experienced surgeons,
about 50 - 60% of all infants will clear their jaundice and
achieve a normal (<20 µmol/L, <2 mg/% according to
definition) bilirubin. These should do well and have a
good quality of long-term survival with their native liver.
In those with no effect from the Kasai (usually only too
apparent within 2-3 months), then active consideration
should be given to early liver transplantation. The
hazards of transplantation in small infants should never
be underestimated and deaths on the waiting-list are still
an ever present threat. Nevertheless a 3-year survival rate
of 85 - 90% post–transplantation is currently achievable
and realistic for this group of children.22,23
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