Diagnostic uncertainty made early surgery for biliary

atresia an area of controversy during the 1960s. Thaler and

Gallis felt that surgical manipulation was deleterious in cases
of neonatal hepatitis and recommended a waiting period of
4 months before exploration for possible biliary atresia.6,7
Other authors also reported that there was a possibility of
spontaneous resolution of biliary atresia, further diminishing
the potential merits of early operation. Finally, some believed
that improved outcomes may be obtained after waiting for the
course of the disease to progress with the hope that any ductal
structures would enlarge, making repair more successful.8–11
Outcomes for infants with “noncorrectable” biliary atresia
remained dismal.
In the late 1950s Kasai and his colleagues in Japan noted
that bile flow from the porta hepatis was possible after excision
of the entire fibrotic extrahepatic biliary tree.12–14 By surgi-
cally connecting the porta hepatis to the intestine (the duode-
num in early cases), Kasai achieved the first long-term “cure”
of a patient deemed to have the noncorrectable form of biliary
atresia. Despite these encouraging initial results, Kasai’s he-
patic portoenterostomy did not gain immediate acceptance.
Surgeons both in Japan and in the United States were initially
skeptical of his results.15,16 Over time, however, the outcomes
CHAPTER 105 associated with Kasai’s hepatic portoenterostomy were con-
firmed17,18 and in its most recent form, using a Roux-en-Y
portoenterostomy, this procedure has become the standard
operative treatment for biliary atresia.
The Jaundiced Because many children develop progressive liver failure
despite a technically well-executed hepatic portoenterostomy,
salvage therapies are often necessary. Liver transplantation,
Infant: Biliary popularized by Starzl in the early 1960s,19 is the only readily
available salvage treatment for children with biliary atresia

Atresia and progressive liver dysfunction. In fact, biliary atresia

is the most common diagnosis leading to liver transplantation
in children.
Robert A. Cowles
Incidence, Demographics,
and Classification
History ------------------------------------------------------------------------------------------------------------------------------------------------

------------------------------------------------------------------------------------------------------------------------------------------------
Jaundice is a common finding in the newborn nursery and
Biliary atresia was first described by John Thompson in in young infants. In a majority of cases this hyperbiliru-
1892.1 He detailed 49 clinical cases of congenital biliary ob- binemia is due to elevated unconjugated bilirubin and
struction and documented the autopsy findings in each case. resolves spontaneously with no need for surgical consultation
In 1916 Holmes, a pediatrician and pathologist at Johns or intervention. It is important, however, to identify the rare
Hopkins University, reported his own case, reviewed previ- infant who has persistent, pathologic jaundice beyond
ously reported cases, and concluded that successful surgical 2 weeks of life. These neonates should be presumed to have
treatment for congenital atresia of the bile ducts was theoret- biliary obstruction due to biliary atresia or choledochal cyst
ically possible in at least 16% of cases.2 Ladd was the first to or a cholestatic process due to a myriad of underlying causes,
report successful surgical correction of biliary atresia in cases and a careful evaluation should be promptly undertaken.
where either the gallbladder or the common bile duct com- Biliary atresia occurs in between 1 in 10,000 and 1 in
municated with the liver.3 This success led him to recom- 16,700 live births and this incidence has been consistent
mend a more aggressive surgical approach to cases of over time.20–22 A slight predominance of females exists with
presumed biliary atresia. Despite this, a majority of infants a female-to-male ratio ranging between 1.4 to 1.7 to 1. No
do not have the favorable anatomy that was described by clear genetic factors have been associated with biliary atresia;
Holmes and Ladd and subsequent large series showed low however, the incidence of the disease appears to be higher in
success rates for surgery in cases of biliary atresia. From Asia than in Europe or North America.
the late 1940s to the early 1960s several creative surgical ap- Several systems have been proposed to classify the anatomy in
proaches attempting to obtain bile drainage from the liver cases of biliary atresia. The Japanese Association of Pediatric
were used, but these were ultimately unsuccessful and sub- Surgeons proposed that cases should be classified according
sequently abandoned.4,5 to the location of atresia. In their system, type I anatomy is
1321
1322 PART VII ABDOMEN

associated with atresia at the level of the common bile duct; TABLE 105-1
in type II, atresia is at the level of the hepatic duct; and Congenital Anomalies Associated with Biliary Atresia
in type III, the most frequent type, atresia occurs at the porta Malrotation
hepatis.22 The common anatomic variations are shown in Preduodenal portal vein
Figure 105-1. Polysplenia
Interrupted inferior vena cava
Azygous continuation
Etiology
------------------------------------------------------------------------------------------------------------------------------------------------
Cardiac malformations

The exact etiology of biliary atresia is unknown and likely

multifactorial. Theories implicating genetic, inflammatory,
and infectious causes have been presented, but none has
been proven. The higher incidence of biliary atresia in certain Embryology
populations makes a genetic cause plausible. Moreover, ------------------------------------------------------------------------------------------------------------------------------------------------

the observation that up to 20% of biliary atresia cases The biliary system originates from the hepatic diverticulum of
are associated with other congenital malformations22 (Table the foregut at 4 weeks’ gestation. This structure differentiates into
105-1) implies a global developmental abnormality that cranial and caudal components, which give rise to the intrahe-
may be under genetic control. Despite this, the occurrence patic and extrahepatic bile ducts, respectively. It is during this
of biliary atresia in twins is exceedingly rare, familial patterns period that the bile ducts undergo recanalization, eventually
have not been seen, and a clear genetic cause has not been leading to an intact biliary tree. Errors in the recanalization
found. process constituted early theories regarding the etiology of
Theories suggesting an acquired, infectious etiology are biliary atresia, but this is no longer believed to be correct.
supported by several findings. First, several viruses such as
reovirus and rotavirus have been proposed as possible infec-
tious agents responsible for the development of biliary atre- Pathology
sia.23,24 Animal models of perinatal viral infection produce ------------------------------------------------------------------------------------------------------------------------------------------------

biliary atresia,25 although consistent viral isolation has not The pathologist plays a central role in the diagnosis of
been possible in human cases.26 In addition, given the high biliary atresia and provides an important assessment of the struc-
prevalence of these viruses, it would be expected that the tures present at the fibrous biliary remnant. Inflammation is in-
incidence of biliary atresia would be higher if, in fact, viral variably seen in liver biopsies and in resected specimens.32–35
infection was causative. Second, it appears that many cases In the appropriate clinical scenario, a percutaneous liver
of biliary atresia are acquired rather than congenital.27 Up biopsy can reliably aid in the diagnosis of biliary atresia. The
to 60% of infants who are found to have biliary atresia have finding of bile ductular proliferation in the liver biopsy is con-
been documented as having pigmented stools sometime sidered diagnostic for biliary atresia.36,37 Associated findings
during the postnatal period.28 Third is the epidemiologic often include bile stasis, periportal inflammation, identification
finding of seasonal clustering of biliary atresia cases during of giant cells, and varying degrees of fibrosis.
the winter months in some studies.29 Histologic evaluation of the fibrous remnant can reveal
Other proposed factors associated with biliary atresia patency or partial patency of ductal structures or complete
include bile duct ischemia, abnormal bile acid metabolism, absence of these structures. This may depend on whether
pancreaticobiliary maljunction, and the effect of certain excision of the remnant occurred before or after inflam-
environmental toxins.30,31 matory obliteration of the extrahepatic ducts. Identifiable

A B C
FIGURE 105-1 Variants of ductal anatomy in biliary atresia. A, The most common pattern. Ducts are in continuity and obliterated from the porta hepatis
to the common bile duct. B, The gallbladder, cystic duct, and distal common bile duct remain patent, but the hepatic ducts and porta are fibrotic. A chol-
angiogram in this case would show duodenal opacification, but no contrast would enter the intrahepatic ducts. C, Fibrous gallbladder with poor-quality
tissue at the porta hepatis. (From Altman RP, Lilly JR, Greenfeld JR, et al: A multivariable risk factor analysis of the portoenterostomy [Kasai] procedure for
biliary atresia: Twenty-five years of experience from two centers. Ann Surg 1997;226:348, discussion 353. Courtesy Lippincott & Wilkins.)
 CHAPTER 105 THE JAUNDICED INFANT: BILIARY ATRESIA 1323

structures that can be found in the biliary remnant include

bile ducts, collecting ductules, and biliary glands.38 Of these,
the ductules are ultimately responsible for bile drainage
after the portoenterostomy procedure and, over time, these
can form stable bile conduits (Fig. 105-2).

Clinical Evaluation
------------------------------------------------------------------------------------------------------------------------------------------------

SIGNS AND SYMPTOMS

The combination of progressive jaundice, acholic stools, dark
urine, and firm hepatomegaly in an infant should raise the
suspicion for the presence of biliary atresia. Jaundice involves
direct hyperbilirubinemia rather than the indirect hyperbilir-
ubinemia seen in neonatal jaundice. In most cases, the perina-
tal course is unremarkable and meconium is described as
normal. In more than 50% of cases, initial stools are consid-
ered pigmented.28 Over time, stools take on a lighter color
and become acholic due to biliary obstruction (Fig. 105-3).
Eventually, signs of advanced liver disease such as palpable
hepatomegaly and splenomegaly, ascites, failure to thrive, FIGURE 105-3 Gross appearance of acholic stool from an infant later
and malnutrition become present. If not treated, biliary atresia confirmed to have biliary atresia.
is fatal within the first 2 years of life with one study reporting a
survival rate of less than 10% at 3 years.20
BLOOD TESTS
DIAGNOSIS
Standard serum “liver function tests” are uniformly obtained,
Children with persistent jaundice, especially those with an but specificity is lacking. In biliary atresia both the direct and
elevated conjugated bilirubin, should be evaluated promptly indirect bilirubin levels are elevated. The transaminases are
to exclude the diagnosis of biliary atresia. No single test can also mildly to moderately increased. Alkaline phosphatase
reliably be used to differentiate biliary atresia from other levels are often elevated in infants and children due to contri-
causes of jaundice in the infant. For this reason, a combination bution from bone remodeling. For this reason, the gamma-
of data obtained from a complete clinical assessment, blood glutamyl transpeptidase (GGTP) level can be used as a more
tests, imaging studies, and pathologic evaluation is often specific indicator of hepatobiliary disease. Unless decompen-
used to arrive at a provisional diagnosis in almost all cases. sated liver disease is present, tests of hepatic synthetic func-
The final diagnosis, however, is always confirmed at surgical tion such as the clotting cascade and serum albumin are
exploration. The following evaluation is recommended as a normal.
useful guide. In order to rule out conditions that can mimic biliary
atresia, screening for perinatal infections due to members of
the TORCH family (Toxoplasmosis, Other viruses, Rubella,
Cytomegalovirus, and Herpes Simplex Virus) should be
performed. In addition, screening for the presence of alpha-1
antitrypsin deficiency should occur.

ULTRASOUND
Abdominal ultrasound is an easily obtained, simple, and non-
invasive imaging study that can aid in the evaluation of infants
suspected of having biliary atresia.39,40 It should be obtained
in the fasting state to allow for filling of the gallbladder,
if patent, and the use of Doppler techniques can improve
the accuracy of the study.40 The echotexture of the liver, the
presence of ascites, the patency of the hepatic vasculature,
and the anatomy of the biliary structures can be assessed.
Although the abdominal ultrasound does not secure a diagno-
sis in most cases, on occasion it can streamline the subsequent
evaluation and management in specific situations. For exam-
ple, the presence of a hilar cystic structure in the clinical
FIGURE 105-2 Schematic showing biliary ductules draining into the setting of obstructive jaundice is sufficient information to pro-
Roux limb as postulated to occur after successful hepatic porto- ceed with surgical exploration with a presumptive diagnosis
enterostomy. (Courtesy M. Kasai, MD) of cystic biliary atresia or choledochal cyst with obstruction.
1324 PART VII ABDOMEN

In either scenario, relief of biliary obstruction should be assessment or, on rare occasions, at exploration when the
provided as soon as feasible. Alternatively, an ultrasound diagnosis cannot be confirmed preoperatively.
appearance of dilated proximal bile ducts suggests the pres-
ence of inspissated bile syndrome, which may be treated by
observation or, if needed, operative cholangiogram with or Other Tests
without biliary irrigation. ------------------------------------------------------------------------------------------------------------------------------------------------

In almost all infants with biliary atresia, however, the A combination of the previously described tests constitutes
ultrasound reveals that the gallbladder is either shrunken or an adequate evaluation for biliary atresia, and operative
normal appearing and the bile ducts are not easily delineated. therapy can be planned on the basis of these data. In some
In selected centers with extensive experience in the use of centers, however, other diagnostic modalities have been pro-
ultrasound in biliary atresia, an abnormal “cord” can be posed. These adjunctive tests may be performed in certain
appreciated in the area of the portal plate.41 circumstances but should not be considered part of the rou-
tine evaluation for biliary atresia.
Intubation of the duodenum via the nasoduodenal route with
aspiration or prolonged collection of duodenal fluid can exclude
HEPATOBILIARY SCINTIGRAPHY
biliary atresia if bile-stained fluid is obtained.45 Although simple,
Hepatobiliary scintigraphy relies on the use of isotopes of this test is invasive, subjective, and similar in concept to the
technetium 99m to assess excretion of bile from the liver into DISIDA scan, which is easily obtained in most centers.
the small intestine and therefore biliary patency. The term Endoscopic retrograde cholangiopancreatography (ERCP)
“HIDA” (hydroxy iminodiacetic acid) scan is often used, but is a technique that is widely applied in the evaluation of biliary
the technetium-labeled compound diisopropyl iminodiacetic diseases in adults and older children. With improvements in
acid (DISIDA) is more effective in the presence of significant endoscopic instrumentation, small side-viewing endoscopes
cholestasis and therefore more commonly used. The use- that can be used in infants are available. Some authors have
fulness of all hepatobiliary scintigraphy is diminished in the proposed ERCP as a useful adjunct in avoiding unnecessary
presence of severe jaundice, and this may cause errors in exploration for presumed biliary atresia.46 Because other
interpretation. less-invasive tests yield an accurate diagnosis in almost all
If time allows, all jaundiced infants undergoing hepatobili- cases, however, the practical use of ERCP is actually quite lim-
ary scintigraphy should be pretreated with phenobarbital ited and is not currently recommended. Magnetic resonance
(5 mg/kg/day) for 5 days before the study.42 Presence of iso- imaging (MRI) techniques such as magnetic resonance cho-
tope in the intestine immediately confirms patency of the bil- langiopancreatography (MRCP) have superior accuracy in
iary system, and the diagnosis of biliary atresia can be the diagnosis of biliary atresia.47 MRI and MRCP, however,
excluded. Excretion of isotope may be delayed, however, in are expensive, sometimes require sedation, and have not been
the presence of liver dysfunction. For this reason, a delayed routinely used in most centers.
assessment of isotope excretion at 24 hours is warranted.
When no isotope is seen in the intestine after 24 hours, biliary
obstruction is presumed and the diagnosis of biliary atresia
must be further pursued.
Treatment
------------------------------------------------------------------------------------------------------------------------------------------------

PREOPERATIVE CARE
Infants with presumed biliary atresia should be prepared for
Liver Biopsy exploration soon after diagnostic testing has been completed.
------------------------------------------------------------------------------------------------------------------------------------------------
Standard presurgical measures should be taken and, in gen-
A percutaneous liver biopsy can help differentiate biliary eral, children can be admitted on the day of surgery. A bowel
atresia from other cholestatic conditions with a high degree preparation is not required, but a dose of broad-spectrum an-
of reliability and should be considered the most accurate tibiotics should be administered before making the abdominal
nonsurgical diagnostic test.43,44 It is the most invasive of incision. Although most infants diagnosed with biliary atresia
the diagnostic modalities but can be performed safely by an will have normal coagulation studies, poor absorption of the
experienced pediatric hepatologist, or, if needed, by the sur- fat-soluble vitamin K can theoretically render them function-
geon. Typically, examination of several portal tracts by a ally vitamin K deficient. If possible, preoperative oral sup-
well-trained pathologist will reveal important findings that plementation with fat-soluble vitamins (A, D, E, and K) or
can confirm or exclude biliary atresia. The presence of varying an intramuscular injection of vitamin K (1 mg) should be
degrees of inflammation with ductular proliferation is consid- considered.
ered compatible with the diagnosis of biliary atresia because
these findings are not seen in other nonobstructive cholestatic
SURGICAL TECHNIQUE
syndromes. Further findings of bile stasis with plugging and
giant cell transformation further support the diagnosis of bil- The Roux-en-Y hepatic portoenterostomy procedure (Kasai
iary atresia. On the basis of the appearance of the liver biopsy, Procedure) is the standard initial operation for treatment of
bile duct paucity syndromes can be readily differentiated from infants with biliary atresia. The operation involves excision
biliary atresia. In contrast, however, it can be difficult to of the entire extrahepatic biliary tree with transection of the
differentiate between parenteral nutrition-associated cholesta- fibrous portal plate near the hilum of the liver. Bilioenteric
sis and biliary atresia on the basis of liver biopsy alone. This continuity is then reestablished with a Roux-en-Y limb.13
distinction should be made on the basis of the overall clinical The ultimate goal of the procedure is to allow drainage of bile

from the liver into the Roux limb via microscopic ductules
in the portal plate. The conduct of the operation is described
as follows.
The infant should be placed supine and on an operating
table that will permit operative cholangiography, if deemed
necessary. The exploration begins via a right upper abdominal
incision. The left upper quadrant is examined, first searching
for the spleen. Absence of the spleen or the finding of poly-
splenia can alert the surgeon to the presence of important
associated anomalies such as malrotation, preduodenal portal
vein, and interrupted inferior vena cava with azygous contin-
uation. During evaluation of the left upper quadrant, adequate
position of the tip of the nasogastric tube is also confirmed and
the tube is secured by the anesthesiologist.
Next, the liver, biliary structures, and porta are inspected.
The liver in biliary atresia can appear nodular and fibrotic with
a greenish color. This finding is not common in neonatal
hepatitis or bile duct paucity syndromes, where the liver is
smooth and dark brown in color. Many infants with biliary
atresia have a contracted, fibrotic gallbladder. If a rudimentary
fibrous gallbladder is noted at initial exploration and if it
clearly has no lumen, then the diagnosis of biliary atresia
has been confirmed and the operation can proceed with
dissection of the portal plate. If the gallbladder is normal-
appearing or if it is felt to have a lumen, then additional intrao-
perative diagnostic maneuvers are warranted before dissecting
the portal plate. In this situation, a purse-string suture can be
placed in the fundus of the gallbladder and the fluid within the
lumen of the gallbladder aspirated with an angiocath. If clear
fluid (white bile) returns, then our approach has been to
proceed with portal plate dissection without a cholangiogram.
If, however, the aspirated fluid is darker in color or if there
is any ongoing question regarding the diagnosis, then a chol-
angiogram should follow.
Although simple in concept, the cholangiogram can be
difficult to perform and interpret successfully during this
exploration. The following steps can be used to maximize
the diagnostic yield of the intraoperative cholangiogram. First,
a secure purse-string suture should be placed. A second
purse-string suture can also be placed to prevent contrast leak-
age. Either an angiocath or a laparoscopic cholangiogram
catheter can be placed into the lumen of the gallbladder before
tying the purse-string suture(s). Diatrizoic acid (Hypaque or
Gastrografin) is diluted 1:1 with normal saline and injected
as the contrast agent via the cholangiogram catheter to assess
for patency or obstruction of the biliary tree. Real-time, live
fluoroscopy facilitates rapid intraoperative interpretation of
the study. If contrast flows freely into the duodenum and into
intrahepatic bile ducts, then patency of the biliary tree has
been established and the diagnosis of biliary atresia excluded
(Fig. 105-4). In this scenario, a wedge liver biopsy should
be performed, the cholangiogram catheter removed, the
cholecystotomy closed, and the operation concluded.
On occasion, contrast will flow freely into the gallbladder
and down the distal common bile duct into the duodenum but
not proximally into the intrahepatic bile ducts. This finding
should be confirmed by occluding the distal common bile
duct with an atraumatic “bulldog” clamp and reinjecting the
cholangiogram catheter. This maneuver may encourage
preferential filling of any patent proximal ducts that may have
initially failed to opacify with contrast material when the distal
resistance to flow was low. It is important to inject contrast
CHAPTER 105 THE JAUNDICED INFANT: BILIARY ATRESIA 1325
FIGURE 105-4 Cholangiogram obtained during abdominal exploration
for presumed biliary atresia. The gallbladder (GB) appeared normal, and an
intraoperative cholangiogram revealed patency of the intrahepatic ducts
to the duodenum (Duo). A liver biopsy was performed, and the procedure
was concluded.
gently because a speedy injection under pressure is likely to
cause leakage of contrast around the purse-string suture,
resulting in an obscured and confusing cholangiogram. Failure
to delineate patent intrahepatic and extrahepatic biliary struc-
tures mandates that the surgeon proceed with portal dissection.
Regardless of the presence of a patent gallbladder or distal
common bile duct, a direct Roux-en-Y hepatic portoenterost-
omy affords outcomes that are superior to other forms of
reconstruction such as the portocholecystostomy.48 Some
surgeons gain exposure by dividing both triangular ligaments,
thereby exteriorizing almost the entire liver.49,50 This step is
not necessary and likely disrupts lymphatics that may be re-
sponsible for the development of ascites. We have found that
upward retraction of the liver to expose the porta affords
excellent visualization of the critical structures and can be
accomplished by assigning an assistant for retraction in the
right upper surgical field or by carefully placing a fixed metal
retractor with upward traction.
The peritoneum overlying the hepatoduodenal ligament is
opened to allow identification of the structures in this area.
The fibrous remnant of the distal common bile duct is often
present here. It can be identified in the anterolateral aspect
of the hepatoduodenal ligament, isolated and divided. Care
should be taken to avoid injury to aberrant hepatic arteries
that may be nearby. With traction on the cut end of the oblit-
erated distal common bile duct, the fibrous biliary remnant
can be dissected toward the porta. It is often necessary to
dissect the right and left hepatic arteries away from the field
in order to preserve them. During this dissection, the gallblad-
der remnant is also dissected away from the liver in continuity
with the rest of the extrahepatic biliary remnant. As dissection
continues proximally, the biliary remnant develops into a cone
of fibrotic tissue that is located at the bifurcation of the main
portal vein into its left and right branches. This constitutes the
most important landmark during the dissection of the portal
plate and should be the goal of every dissection.51,52 In this
1326 PART VII ABDOMEN

location it may be necessary to control several small portal

vein branches to avoid inadvertent injury with subsequent
bleeding. The absence of identifiable biliary remnant tissue
or the finding of poor quality tissue at the expected location
of the portal plate sometimes confuses the dissection. As
stated earlier, the bifurcation of the portal vein should be
used as a landmark and is especially important in such cases
where the biliary remnants and portal plate are difficult to
identify clearly.
Once the fibrous cone and portal plate region have been
identified, the fibrous cone is placed on gentle traction and
transected with sharp scissors or a knife. It is not beneficial
to cut deeply toward the liver parenchyma because this may
result in more scar formation and inhibition of bile drainage.
Bleeding at the transected portal plate is controlled with pres-
sure and placement of a surgical sponge in the area. Use of
cautery on the portal plate is discouraged and should be min-
imized because this structure contains the fine ductules
needed for success of the procedure. The resulting surgical
specimen should be marked and submitted for routine path-
ologic evaluation. Careful measurement of the diameter of any
biliary ductules by an experienced pathologist should be
requested because this may provide important prognostic in-
formation. Although advocated by some,53 we have not found FIGURE 105-5 Artist’s rendition of the completed hepatic portoenter-
frozen section to be helpful in guiding the level of transection. ostomy procedure.
With a completed portal plate dissection, the operation
shifts to the construction of the Roux limb. The proximal je-
junum is identified and transected about 10 centimeters distal
to the ligament of Treitz. The distal end, destined for the right valves28,55–57 have been subsequently abandoned either due
upper quadrant, is oversewn and the Roux limb is measured to to associated complications or lack of effectiveness.58–60
40 to 50 centimeters.54 At this location, an end-to-side jejuno- Similarly, use of the appendix as a conduit between the liver
jejunostomy is created with interrupted absorbable sutures. and the small intestine has been proposed but its use has
The oversewn end of the Roux limb is carefully brought been limited with some reports suggesting an inferior surgical
into the right upper quadrant via a small defect created in outcome.61
the avascular portion of the transverse mesocolon. With the widespread application of minimally invasive
The side of the Roux limb is opened, and the portoenter- techniques, even to the most complex operations, the laparo-
ostomy is created. The posterior suture line is placed first scopic Kasai procedure has been described and used at
using 6-0 absorbable suture with knots tied inside the lumen. several centers worldwide.62,63 Most reports, however, in-
Placement of these sutures must be exact with care taken to volve single cases or small series of carefully selected patients.
avoid injuring or impinging on the portal tissue. Once this A recent prospective trial confirmed the feasibility of the
posterior row is complete, the anterior sutures can be placed operation but revealed a significantly poorer outcome at
using similar care and precision. When complete, the entire 6 and 24 months, causing the trial to be stopped.64 Outcomes
surface of the portal plate must be contained within the jejunal of other series have been variable,65 and therefore the lapa-
lumen of the Roux limb. In this way, any bile drainage via roscopic Kasai procedure currently lacks support among
biliary ductules at the portal plate will be contained within general pediatric surgeons including those who specialize in
the Roux limb and proceed distally. minimally invasive pediatric surgery. Laparoscopic techniques
Before closure, it is advisable to close the mesenteric may be used to perform the exploration and cholangiogram.
defect created by construction of the Roux limb and to anchor Some investigators have proposed that primary liver
the Roux limb to the edges of the defect in the transverse transplantation be considered the initial treatment for infants
mesocolon. These maneuvers are aimed at preventing internal with biliary atresia, citing deleterious effects of the Kasai
herniation and at keeping the Roux limb in the right upper procedure on subsequent liver transplantation, if needed.
quadrant and without tension. A small closed suction drain This approach, however, would subject a percentage of chil-
is placed near the portoenteric anastomosis, and a wedge liver dren to the dangers of transplantation and its associated
biopsy is routinely performed but likely not absolutely short- and long-term complications who would have been
necessary. The abdomen is then closed using standard tech- cured by the Kasai procedure. For this reason, primary liver
niques. The completed operation is shown in (Fig. 105-5). transplantation has been reserved for selected cases such as
delayed diagnosis with severe liver failure where a Kasai
procedure would be risky and have a high failure rate.66–68
SURGICAL CONTROVERSIES
For all other children with compensated liver function and a
Much of the controversy surrounding surgery for biliary timely diagnosis, the Kasai procedure and liver transplant
atresia has subsided. Previously reported techniques with are considered by most to be sequential, complementary
stomas to exteriorize the Roux Limb28 or antireflux procedures.69

POSTOPERATIVE CARE
Drainage of gastric secretions with a nasogastric tube should
continue for the first 48 hours, and the tube can usually be re-
moved at this point. By the second or third postoperative day,
infants often have already passed gas and stool and an oral diet
can be started. Intravenous antibiotics are administered until
the child begins feeding, and this is subsequently converted
to long-term oral antibiotics that are continued at discharge.
The closed suction drain is removed before discharge, typically
on the fifth postoperative day. Antibiotics, a choleretic agent,
fat-soluble vitamin supplements, and an oral steroid taper
have been the routine for our group (Table 105-2), although
the support for the use of steroids is not universal as discussed
in the next section.
STEROID CONTROVERSY
Steroids are known to have antiinflammatory and immuno-
suppressive effects. Their use in patients with biliary atresia
with its significant inflammatory component is therefore
logical. In addition, steroids have been postulated to have a
choleretic effect, making them even more attractive in this pa-
tient population. Despite this, definitive evidence for the ben-
eficial effects of adjunctive steroids in biliary atresia has been
elusive. First, attempts to prove the choleretic action of ste-
roids were not successful.70 Second, many studies comment-
ing on the efficacy of steroids are retrospective and contain
confounding factors that make it impossible to comment on
the isolated effects of steroid treatment. Finally, studies often
appear underpowered to allow definitive conclusions.71,72
For these reasons, it is not surprising that one study found that
perioperative steroids were used in less than 50% of patients
in the United States between 2003 and 2008.73
The paucity of data regarding the utility of steroids may be
changing, however. A recent randomized, double-blind,
placebo-controlled trial of corticosteroids after hepatic por-
toenterostomy revealed that steroids resulted in accelerated
clearance of jaundice but did not result in improved survival
of the native liver.74 A current study by the biliary atresia re-
search consortium in the United States is also attempting to
address this question systematically. The results are pending.
Adverse sequelae of steroid use are not commonly
reported. Fluid retention and appetite suppression are minor
side effects, but major steroid-related complications such as
infection and wound breakdown have not been problematic.
Given that the evidence supporting steroid use is currently
stronger than the evidence against it, our group has incor-
porated a protocol for postoperative steroid administration
(see Table 105-2).
TABLE 105-2
Postoperative Medical Regimen After Hepatic
Portoenterostomy
Ursodiol (Actigall)—10-15 mg/kg/dose BID day
Trimethoprim-Sulfamethoxazole—2.5 mg/kg/day based on
Trimethoprim component dosing
Vitamins ADEK drops—1 mL/day
Prednisone—2 mg/kg/day and taper over 6 weeks
CHAPTER 105 THE JAUNDICED INFANT: BILIARY ATRESIA 1327
Outcomes
------------------------------------------------------------------------------------------------------------------------------------------------
Over the past 50 years, the hepatic portoenterostomy proce-
dure has dramatically improved the outlook for infants diag-
nosed with biliary atresia. Before the introduction of the
hepatic portoenterostomy, few surgical options were available
for treating infants with biliary atresia. A review of 89 patients
who were explored for biliary atresia before the advent of
formal surgical correction revealed a “cure” rate of 1.1%
(1 of 89) and a known mortality of 94% (84 of 89).75 The cur-
rent 30-day mortality is low, ranging between 0% and 5%,
reflecting the safety of the hepatic portoenterostomy.61,69
An important initial observation is the color of the stool
after hepatic portoenterostomy. Pigmented stools either imme-
diately or within the first 10 to 14 days after surgery suggest
successful bile flow from the liver to the intestinal tract. This
occurs in two thirds of patients, on average.59,61,69 Of these
patients who have documented bile flow, half will continue
to drain bile well, with efficient clearance of jaundice and
normal development. This is considered a “cure,” and liver
transplantation is not necessary.
In the remaining patients who initially had good bile drain-
age, ongoing inflammation and scarring of the liver will lead to
progressive liver failure. Jaundice, which may have initially
cleared completely or partially, returns. Signs of portal hyper-
tension and failure to thrive eventually appear, and liver
transplantation is therefore required. In this patient popula-
tion that had initial successful palliation, liver transplantation
occurs at a mean age of 5.4 years.69
The remaining patients (15% to 30%) who continue to
have acholic stools after hepatic portoenterostomy never expe-
rience clinically relevant bile drainage. Jaundice continues to
worsen, and the liver fails within months. In these infants an
evaluation for liver transplantation, either cadaveric or living
related, should commence before the arrival of true end-stage
liver disease.
The 10-year survival after hepatic portoenterostomy has
improved over time. Initial improvements were likely due to
refinement of the portoenterostomy procedure, while more
recent gains have been made in the technique of liver trans-
plantation and in immunosuppressive strategies and medi-
cations. A biliary atresia registry report from the United
States in 1990 found 5- and 10-year survival rates of 48%
and 30%, respectively,20 while a report from our center in
1997 found a 20-year survival rate of 49%.69 A recent multi-
center study in the United States reported a 2-year overall
survival rate of 91% with a 56% native liver survival and
40% liver transplant rate.76 Studies from other countries
including Japan quote similar statistics.21,22,56,61,77
Long-term patient outcomes beyond liver function are
available. Abnormalities in menstruation and pubertal dis-
orders occur and are closely related to liver function. These
findings suggest that hepatic function is deteriorating and
transplantation will eventually be necessary. When transplan-
tation occurs, menstrual abnormalities have been shown to
improve.78 Pregnancy can be challenging for patients who
have been treated with hepatic portoenterostomy for biliary
atresia. Progression of liver disease with development of portal
hypertension has been documented during gestation.78 New-
borns can be small but are generally healthy. The postpar-
tum period has also been documented as complicated.79
1328 PART VII ABDOMEN
These data suggest that great care should be taken in counsel-
ing former biliary atresia patients regarding pregnancy, and
careful monitoring is indicated when pregnancy is being
considered.
Psychosocial outcomes have been reported in long-term
survivors of the hepatic portoenterostomy.78 This study of
44 patients with long-term follow-up revealed that almost
all patients (93%) are functioning well in society with high
levels of employment and education. Psychologic morbidity
was present, however, in 18% of this population.
OUTCOME VARIABLES
A variety of factors appear to play a role in the outcome after
hepatic portoenterostomy for biliary atresia. Age at operation,
operative technique, severity of liver disease, gross and micro-
scopic aspects of the biliary tree and portal plate, and the
presence of comorbid conditions are a few of the many
variables that can affect outcome.
Strong evidence suggests that age at operation is an impor-
tant factor in outcome, and this is supported by multiple
reports.69,80–84 The exact cutoff, however, where outcome
from surgery becomes predictably poor, is unknown. This
may be due to the existence of several distinct pathologic
forms of biliary atresia. In fact, recent studies suggest that
age at surgery may be a factor only in certain subsets of
children such as those with cystic biliary atresia or those with
biliary atresia splenic malformation as compared with those
who present with isolated biliary atresia.85 In our series, in-
fants operated on at 0 to 49 days had equivalent outcomes
when compared with those who underwent operation at 50
to 70 days of age. Those explored at 71 days or older had a
statistically higher rate of failure when compared with both
of the younger groups.69 In the Japanese experience, the better
outcomes were seen until the age of 90 days with subsequent
worsening outcome after 90 days.22 Therefore it is the goal at
most centers to accurately obtain a provisional diagnosis of
biliary atresia and successfully operate before 70 to 90 days
of life. It is important to note, however, that hepatic portoen-
terostomy is not contraindicated after 90 days of age. A study
of older children (100 days) revealed acceptable survival
rates, supporting the use of the procedure, if possible, even
in older infants.86
The gross appearance of the biliary tree appears to influ-
ence outcome. Patients with a patent gallbladder had better
outcomes when compared with those with complete fibrosis
or complete absence of the fibrous cone of the portal plate.16
The size of ductules that are present at the level of the portal
plate seems to be related to prognosis. It is logical that larger
ductules allow for more efficient drainage of bile and therefore
would result in an overall better outcome. Our series found
that bile drainage was universal in patients with ductules
greater than 150 micrometers, occurred in 86% of those with
ductules less than 150 micrometers, but was only seen in 12%
of those with no identifiable ductules.69 Other studies have
supported these findings.34,38,87–90
The experience of the surgeon and the center has been
suggested as a factor in outcome of hepatic portoenterostomy.
Our study revealed inferior outcomes in patients who had
surgery in the 1970s, possibly reflecting a learning curve
regarding surgery and the care of these patients.69 Recent
studies in the United Kingdom91 and in France92 also suggest
that experienced centers and centralization of care for pa-
tients with biliary atresia produce superior outcomes. These
national health policies, however, have not been implemented
in many countries and long-term outcome differences are
pending.
Complications
------------------------------------------------------------------------------------------------------------------------------------------------
NUTRITIONAL COMPLICATIONS
Nutrition with a well-functioning hepatic portoenterostomy
follows a normal course. Specialty formulas and vitamin
supplements, if used, can often be discontinued after several
months without harm. In the face of ongoing or progressive
liver dysfunction, however, weight gain can be affected and
metabolic complications may occur.93 Nutritional parameters,
vitamin levels, and growth should be monitored over the long
term. In fact, some authors suggest that growth failure is an
important marker for liver disease and an indication for liver
transplantation in biliary atresia.94
CHOLANGITIS
Cholangitis is the most common complication of the
hepatic portoenterostomy and occurs in 33% to 60% of
patients.54,77,95 Cholangitis occurs most frequently during
the first several years after initial surgery. Because cholangitis
causes liver injury and promotes accelerated development
of cirrhosis, prevention and active treatment are important
adjuncts during the postoperative period.
The exact cause of cholangitis is unknown, although reflux of
intestinal contents via the Roux limb, portal venous infection,
impaired lymphatic drainage at the porta, and bacterial trans-
location have been proposed. Intrahepatic biliary stasis due to
the fibrotic ductal obstruction is also felt to play a role in the
pathogenesis of cholangitis. The offending organisms have
been identified as enteric gram-negative and anaerobic bacteria,
further supporting an enteric source for the condition.96
The clinical signs of cholangitis include fever, diminished bile
flow, jaundice, and sometimes abdominal pain. Blood testing will
reveal leukocytosis, elevated serum bilirubin, elevated hepatic
enzymes (transaminases, alkaline phosphatase, and GGTP),
and inflammatory parameters such as C-reactive protein.
Treatment of cholangitis is aimed at the presumed infection
and the ongoing inflammation. The mainstay of treatment
includes intravenous fluids, broad-spectrum intravenous
antibiotics including coverage of anaerobes, and choleretic
agents. Steroids are indicated for their ability to decrease
inflammation and edema of the periductular areas.97
Prevention of cholangitis is an important goal. An ade-
quately constructed Roux limb is a surgical maneuver that aids
in prevention of cholangitis. Similarly, postoperative use of
oral antibiotics is generally felt to be efficacious as a preventa-
tive measure. Studies have shown that use of trimethoprim-
sulfamethoxazole or neomycin appeared to delay the onset
and reduce the number of episodes of cholangitis compared
with historic controls.98 The use of steroid pulses during
the postoperative period has also decreased the frequency of
this complication.99
A surgical approach to revise a failing hepatic portoenter-
ostomy with recurrent jaundice or unrelenting cholangitis

has been attempted.48,100 Hasegawa reported the results of
attempted revision of the hepatic portoenterostomy in
25 patients who did not drain effectively after the initial
operation.101 Only five patients had improvement in jaundice,
a similar result to a series from the United States in which two
of seven children were helped by a re-do portoenterostomy.48
A similarly low success rate has been shown for surgical
revision of the hepatic portoenterostomy in children who
develop severe, intractable cholangitis.22,102 Given these dis-
couraging outcomes, the possibility that repeated operations
can negatively affect the eventual success of liver transplanta-
tion, and in an era where liver transplantation has improved
dramatically, operative approaches to rescue a failed or failing
portoenterostomy are not recommended.
PORTAL HYPERTENSION
Portal hypertension occurs in 34% to 76% of children and
young adults after hepatic portoenterostomy and can occur
despite a seemingly excellent result from the point of view
of bile drainage.103,104 Ongoing intrahepatic inflammation,
often manifested as recurrent cholangitis, is likely responsible
even when jaundice clears.
The most common finding in patients with portal hyper-
tension is ascites, occurring in more than 60%. Esophageal
varices, the most feared sequela of elevated portal pressure,
occur in nearly half of patients who are followed for more than
3 years. Surveillance endoscopy therefore is indicated,
especially in cases where progressive liver dysfunction is
suspected. No clear recommendations are available for the
frequency of surveillance endoscopy; however, yearly or semi-
annual examinations have been recommended. When varices
are identified endoscopically, prophylactic sclerotherapy has
shown benefit in randomized trials.105
Bleeding from esophageal varices can be massive and life
threatening. Treatment consists of endoscopic sclerotherapy,
often requiring multiple sessions.77 Other interventions
that can aid in treatment include use of octreotide or beta-
adrenergic blockers or variceal ligation.106–108 Although con-
cerning, variceal bleeding should not prompt urgent
consideration of liver transplantation and does not signify
the arrival of end-stage liver disease.77
Portal hypertension–associated hypersplenism occurs in
16% to 35% of patients after portoenterostomy, and the asso-
ciated thrombocytopenia can complicate episodes of gastroin-
testinal bleeding from varices or other causes.109 Although
splenectomy, portosystemic shunting, and splenic emboliza-
tion have been described,110 evaluation for liver transplan-
tation is the most prudent option in patients who develop
this serious secondary complication of portal hypertension.
LIVER TRANSPLANTATION
Liver transplantation is covered in a separate section of this
textbook. Nevertheless, it is mentioned here because liver
failure due to biliary atresia represents the most common
indication for liver transplantation in the pediatric age group.
The general indications for liver transplantation in biliary
atresia include (1) failure of initial portoenterostomy with
no bile drainage and progressive liver disease; (2) episodic
CHAPTER 105 THE JAUNDICED INFANT: BILIARY ATRESIA 1329
or inefficient bile drainage with slow deterioration of liver
function and development of growth failure; and (3) develop-
ment of one or more complications of chronic liver disease
such as cholangitis or portal hypertension that cannot be easily
managed despite an apparently functional portoenterostomy.
Thankfully, death on the transplant waiting list is uncom-
mon. Improvements in allocation of organs using the pediatric
end-stage liver disease system, based on several markers of
severity of disease, result in transplantation in the most se-
verely affected first. In addition, two techniques have resulted
in an increase in the number of available organs. First was the
technique of splitting or rescuing the size of organs for use in
children,111 and the second is the development of living-
related liver transplantation.112 These techniques have been
applied in liver transplantation programs worldwide with
excellent success.113–115
With continual improvement in the outcomes of pediatric
liver transplantation, some have questioned whether primary
liver transplantation without an initial attempt at hepatic
portoenterostomy is indicated.68,116,117 At this juncture,
however, most believe that a well-executed hepatic porto-
enterostomy is the best initial surgical treatment for biliary
atresia. This opinion is based on several important observa-
tions: (1) Nearly half of infants who undergo hepatic portoen-
terostomy obtain bile drainage and maintain either excellent
or adequate liver function after surgery. Even in those who
eventually progress to end-stage liver disease, transplantation
is delayed by having undergone hepatic portoenterostomy
first; (2) The improved but still insufficient supply of donor
organs would make primary liver transplantation logistically
challenging; and (3) A subset of children who would have
been “cured” by the hepatic portoenterostomy would be un-
necessarily exposed to the morbidity (surgical, infectious,
and oncologic) and mortality of liver transplantation. At this
point, therefore, liver transplantation remains the most impor-
tant rescue therapy for children with biliary atresia after
portoenterostomy with 5-year survival rates expected to
exceed 90%.118,119
Acknowledgments
The author would like to acknowledge R. Peter Altman, MD, for his priceless
guidance and education on the treatment of infants with biliary atresia.
The complete reference list is available online at www.
expertconsult.com.
SUGGESTED READING
Altman RP, Lilly JR, Greenfeld J, et al. A multivariable risk factor analysis of the
portoenterostomy (Kasai) procedure for biliary atresia: Twenty-five years of
experience from two centers. Ann Surg 1997;226:348.
Davenport M, Caponcelli E, Livesey E, et al. Surgical outcome in biliary atresia:
Etiology affects the influence of age at surgery. Ann Surg 2008;247:694.
Davenport M, De Ville de Goyet J, Stringer MD, et al. Seamless management of
biliary atresia in England and Wales (1999-2002). Lancet 2004;363:1354.
DeRusso PA, Ye W, Shepherd R, et al. Growth failure and outcomes in infants
with biliary atresia: A report from the Biliary Atresia Research Consortium.
Hepatology 2007;46:1632.
Kasai M, Kimura S, Asakura Y, et al. Surgical treatment of biliary atresia.
J Pediatr Surg 1968;3:665.
Kuroda T, Saeki M, Nakano M, Morikawa N. Biliary atresia, the next genera-
tion: A review of liver function, social activity, and sexual development in
the late postoperative period. J Pediatr Surg 2002;37:1709.
1330 PART VII ABDOMEN

Majd M, Reba RC, Altman RP. Hepatobiliary scintigraphy with
99mTc-PIPIDA in the evaluation of neonatal jaundice. Pediatrics
1981;67:140.
Nio M, Ohi R, Miyano T, et al. Five- and 10-year survival rates after surgery for
biliary atresia: A report from the Japanese Biliary Atresia Registry. J Pediatr
Surg 2003;38:997.
Schneider BL, Brown MB, Haber B, et al. A multicenter study of the
outcome of biliary atresia in the United States, 1997 to 2000. J Pediatr
2006;148:467.
Serinet MO, Broué P, Jacquemin E, et al. Management of patients with biliary
atresia in France: Results of a decentralized policy 1986-2002. Hepatology
2006;44:75.