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ORIGINAL RESEARCH
Biliary Atresia: US Diagnosis1

# PEDIATRIC IMAGING
Terry M. Humphrey, MHSC, DMU, DCR
Purpose: To evaluate prospectively the sensitivity of ultrasonogra-
Mark D. Stringer, MS, FRCS, FRCPCH
phy (US) in the diagnosis of biliary atresia (BA), with
surgery as the reference standard.

Materials and After institutional ethical approval and with informed pa-
Methods: rental consent, 90 consecutive fasting infants with conju-
gated hyperbilirubinemia underwent detailed US studies
performed by a single operator with a 7.5-MHz curvilinear
transducer and a 13.5-MHz linear-array transducer. The
following features were prospectively recorded: gallblad-
der morphology, triangular cord sign, presence of a com-
mon bile duct, liver size and echotexture, splenic appear-
ance, and vascular anatomy. The operator was blinded to
results of other investigations. Sensitivity, specificity, and
positive and negative predictive values were calculated for
each US variable. BA and non-BA groups were compared
by means of the Fisher exact test for categorical variables
and an unpaired t test for continuous variables.

Results: Thirty infants (13 male, 17 female) had surgically con-


firmed BA, and 60 (35 male, 25 female) had other docu-
mented causes of neonatal jaundice; the mean ages at US
assessment were 48.5 and 52.4 days, respectively (P !
.5). Eight US features showed a significant difference be-
tween BA and non-BA groups (P " .001, Fisher exact
test). The features with the greatest individual sensitivity
and specificity, respectively, in the diagnosis of BA were
triangular cord sign (73% and 100%), abnormal gallblad-
der wall (91% and 95%) and shape (70% and 100%), and
an absent common bile duct (93% and 92%). The hepatic
artery diameter was significantly larger in infants with BA
than in those without BA (mean # standard deviation, 2.2
mm # 0.59 vs 1.6 mm # 0.40, P " .001), but portal vein
diameters were not significantly different. By means of all
these US features, 88 of 90 infants were correctly classified
as having or not having BA, for an overall accuracy of 98%.

Conclusion: BA can be distinguished with US from other causes of


conjugated hyperbilirubinemia in 98% of infants if multiple
US features are carefully evaluated.
1
From the Department of Radiology (T.M.H.) and Chil-
dren’s Liver & GI Unit (M.D.S.), St James’s University ! RSNA, 2007
Hospital, Beckett Street, Leeds LS9 7TF, England. Re-
ceived June 17, 2006; revision requested August 21;
revision received September 27; accepted November 1;
final version accepted January 19, 2007. Address corre-
spondence to T.M.H. (e-mail: teresa.humphrey@leedsth
.nhs.uk).

" RSNA, 2007

Radiology: Volume 244: Number 3—September 2007 845


PEDIATRIC IMAGING: US Diagnosis of Biliary Atresia Humphrey and Stringer

T
he evaluation of infants suspected associated with polysplenia, situs inver- phy, liver function testing, and histo-
of having biliary atresia (BA) is sus, an interrupted inferior vena cava, logic findings after liver biopsy. The
challenging because no single pre- and other cardiovascular anomalies. equipment used was a US system (Sono-
operative investigation enables the diag- Furthermore, infants with BA typically line Elegra; Siemens, Washington, DC)
nosis to be made with certainty. Liver have a degree of hepatic fibrosis or cir- with a 7.5-MHz multifrequency curvi-
biochemistry assessment, biliary radio- rhosis, and the majority have some evi- linear transducer and a 13.5-MHz mul-
nuclide excretion scanning, magnetic dence of portal hypertension as early as tifrequency linear-array transducer. In-
resonance cholangiography, endoscopic 8 weeks of age (7); these pathologic fants were not fed for 4 hours before
retrograde cholangiography, percutane- changes may sometimes be evident at their examinations because it was thought
ous needle liver biopsy, and laparos- US. Finally, hypertrophy of the hepatic that the gallbladder could be assessed
copy can all be helpful, but their results artery has been reported in infants with more easily when it was not contracted.
are not individually diagnostic. The di- BA (8). The purpose of our study was to None of the infants were sedated.
agnosis of BA is usually suggested after evaluate prospectively the sensitivity of The gallbladder was interrogated
results of several of these investigations US in the diagnosis of BA, with surgery with the 13.5-MHz linear-array trans-
(typically including liver biopsy) have as the reference standard. ducer to assess its shape and the regu-
been reviewed and the diagnosis is con- larity of its wall. An irregular wall and a
firmed at laparotomy. distortion of the gallbladder’s usual
Numerous ultrasonographic (US) Materials and Methods shape were considered abnormal (Fig
features have been described as useful 1). In some instances, irregularity of the
pointers to the diagnosis of BA. Abnor- Study Group gallbladder wall may be subtle (Fig 1c),
malities in the shape and wall of the Between February 2002 and November and it is therefore important that the
gallbladder have, for experienced oper- 2005, consecutive infants with conju- gallbladder is examined with a high-
ators, yielded sensitivities and specifici- gated hyperbilirubinemia of unknown frequency probe. The gallbladder length
ties of more than 90% in the diagnosis cause were prospectively evaluated at was measured. The high-frequency
of BA (1). The triangular cord (TC) our supraregional unit, which is one of transducer was also used to look for the
sign, a focal area of increased echoge- three pediatric liver units in the United TC sign; when present, this sign can be
nicity anterior to the bifurcation of the Kingdom. The study was approved by found by scanning in a transverse
portal vein representing the fibrotic our Institutional Clinical Research Eth- oblique plane and identifying a focal
remnant of the extrahepatic biliary tree ics Committee, and informed parental area of increased echogenicity anterior
in BA, has been considered an impor- consent was obtained. Infants with con- to the bifurcation of the portal vein (Fig
tant diagnostic feature by some (2,3). jugated hyperbilirubinemia of unknown 2). If the common bile duct (CBD) was
Other groups (4) have suggested that a cause undergo a series of investigations visible, its caliber was recorded. Color
combination of three gallbladder fea- to establish the diagnosis. In those sus- Doppler flow imaging was used to help
tures—namely, length less than 19 mm, pected of having BA, the investigations identify the CBD. Liver size and echo-
an irregular wall, and an indistinct mu- include a detailed biochemical and met- texture were assessed; the liver was
cosal lining (the so-called gallbladder abolic workup, an abdominal US scan, a considered to be enlarged if the right
ghost triad)—is diagnostic. radioisotope biliary excretion scan, and lobe extended below the right kidney
In addition to these US features, BA a percutaneous needle biopsy of the
may be associated with other congenital liver. In all cases of BA, the diagnosis
structural anomalies that are detectable was confirmed at laparotomy, the refer- Published online
with US (5). For example, in the BA ence standard. 10.1148/radiol.2443061051
splenic malformation syndrome, as de- Radiology 2007; 244:845– 851
fined by Davenport et al (6), BA can be US Imaging
Abbreviations:
All infants underwent a detailed abdom-
BA $ biliary atresia
inal US examination performed by a sin- CBD $ common bile duct
Advances in Knowledge gle operator (T.M.H., with 10 years of TC $ triangular cord
# An accuracy of 98% can be experience with pediatric US) who was
Author contributions:
achieved in the US diagnosis of blinded to the results of other investiga-
Guarantors of integrity of entire study, T.M.H., M.D.S.;
biliary atresia (BA). tions, such as hepatobiliary scintigra- study concepts/study design or data acquisition or data
# We have shown for the first time, analysis/interpretation, T.M.H., M.D.S.; manuscript draft-
to our knowledge, that the caliber ing or manuscript revision for important intellectual con-
of the hepatic artery is signifi- Implication for Patient Care tent, T.M.H., M.D.S.; manuscript final version approval,
cantly increased in infants with # Accurate diagnosis of biliary atre- T.M.H., M.D.S.; literature research, T.M.H., M.D.S.; clini-
BA compared with the caliber in sia with US may reduce the need cal studies, T.M.H., M.D.S.; statistical analysis, T.M.H.,
M.D.S.; and manuscript editing, T.M.H., M.D.S.
infants with other causes of conju- for invasive procedures such as
gated jaundice. percutaneous needle liver biopsy. Authors stated no financial relationship to disclose.

846 Radiology: Volume 244: Number 3—September 2007


PEDIATRIC IMAGING: US Diagnosis of Biliary Atresia Humphrey and Stringer

Figure 1
(9). Features of portal hypertension,
such as ascites, reversed blood flow in Figure 1: Longitudinal sonograms obtained with
the portal vein, portal vein caliber, 13.5-MHz transducer. (a) Normal gallbladder (arrow)
splenic varices, and splenomegaly, were in 5-week-old infant without BA has normal shape
recorded, and the caliber of the hepatic and regular wall. Calipers and dotted line indicate
artery was noted. Splenomegaly was de- gallbladder length measurement. Bowel (arrowhead)
fined as when the spleen had a length of is seen posterior to the gallbladder. (b) Small, abnor-
more than 6 cm (10). Any features sug- mal gallbladder (arrow) in 8-week-old infant with BA
gestive of the BA splenic malformation has irregular wall and abnormal shape. (c) Abnormal
syndrome (6), such as polysplenia and gallbladder (arrow) in 10-week-old infant with BA.
an interrupted retrohepatic vena cava, Note the more subtle irregularity of the wall (arrow-
were also noted. heads) of this 21-mm-long gallbladder.

Statistical Analysis
Sensitivity, specificity, and positive and
negative predictive values were calcu-
lated for each US variable. The Fisher
exact test was used to determine
whether the frequency of each variable
differed significantly between the BA
and non-BA groups. An unpaired t test
was used to compare normally distrib-
uted continuous variables, such as por-
tal vein and hepatic artery diameters.
The Bonferroni method was used to ad-
just for multiple comparisons. Statisti-
cally significant differences were de-
fined as those with P values less than
.05, and analyses were performed with
statistical software (SPSS, version 12;
SPSS, Chicago, Ill).

Results
A total of 90 infants were evaluated—30
with BA and 60 with other causes of
conjugated hyperbilirubinemia (Fig 3). Figure 2
Clinical characteristics were compared
for the two patient groups at the time of
US scanning; there was no significant
difference (P ! .5) in age between the
groups (Table 1).

BA Group
In all infants with BA (n $ 30), the
diagnosis was confirmed at surgery and
at subsequent histologic examination;
29 infants had type 3 BA (no residual
patent extrahepatic bile ducts), and one
infant had type 1 BA (CBD atresia).
Four had features of the BA splenic mal-
formation syndrome (6) (see below).
Preoperative evaluation included a ra-
Figure 2: TC sign. (a) Transverse sonogram shows TC sign (arrow) in 7-week-old infant with BA. Area of
dioisotope (technetium 99m [99mTc]
increased echogenicity (as indicated by calipers) is seen anterior to bifurcation of portal vein (arrowheads). (b) Sag-
HIDA) biliary excretion scan in 29 in-
ittal sonogram in 10-week-old infant with BA shows TC sign (arrow) superior to portal vein (arrowhead).
fants, which showed no excretion in all

Radiology: Volume 244: Number 3—September 2007 847


PEDIATRIC IMAGING: US Diagnosis of Biliary Atresia Humphrey and Stringer

Figure 3
29, and percutaneous needle liver bi-
opsy in 21 infants. One patient in this
group died of congenital heart disease.
All others were still being followed up at
a median age of 14 months (range, 2– 46
months); 18 were free of jaundice and
were well after a Kasai portoenteros-
tomy, and 11 had undergone successful
transplantation.

Non-BA Group
A wide variety of diagnoses accounted
for conjugated hyperbilirubinemia in
this group of infants (n $ 60) (Table 2).
A radioisotope (99mTc HIDA) biliary ex-
cretion scan was performed in 53 in-
fants (no excretion was found in 23 in-
fants), and a percutaneous needle liver
biopsy was performed in 27. Five in-
fants in this group eventually required
Figure 3: Flow diagram shows US features and outcome in 90 consecutive infants with conjugated hyper-
laparotomy, surgical cholangiography,
bilirubinemia. BASM $ BA splenic malformation syndrome, GB $ gallbladder.
and wedge liver biopsy to exclude BA
definitively. Five infants underwent fol-
low-up elsewhere, and the other 55
were followed up locally for a median of
Table 1
16 months (range, 3– 44 months). In 44
Patient Characteristics at Time of US Assessment of 55 infants, jaundice completely re-
solved (as was confirmed with biochem-
Characteristic BA Group (n $ 30) Non-BA Group (n $ 60)
ical testing). Six infants had persistent
Age (d) 48.5 # 25.6 (18–143) 52.4 # 27 (7–126) jaundice (two each had progressive fa-
Male-to-female ratio 13:17 35:25 milial intrahepatic cholestasis, Alagille
Median gestation (wk) 40 (30–42) 37 (26–42) syndrome, and cystic fibrosis), four in-
Weight (kg) 3.94 # 0.77 (2.2–5.6) 3.11 # 0.92 (1.2–5.5) fants with complex multisystem disor-
Total bilirubin (%mol/L) 160 # 45 (107–303) 133 # 58 (27–386) ders died, and one infant with neonatal
Note.—Unless otherwise specified, data are means # standard deviations, with ranges in parentheses. sclerosing cholangitis underwent suc-
cessful liver transplantation. This group
of patients had a wide spectrum of dis-
orders, and detailed follow-up con-
Table 2 firmed that none had BA.

Causes of Conjugated Hyperbilirubinemia in 60 Infants without BA US Findings


Diagnosis No. of Infants There was a significant difference in the
frequency of each US feature between
Neonatal hepatitis syndrome 22
the BA and non-BA groups (Table 3). In
Prematurity with sepsis and parenteral nutrition 15
two comparisons, detection of the gall-
&1-Antitrypsin deficiency 4
bladder and polysplenia, differences
Alagille syndrome 4
Cystic fibrosis* 3
just failed to reach statistical signifi-
Cytomegalovirus hepatitis 2 cance after adjustment for multiple
Hypopituitarism 2 comparisons. When all US features
Neonatal sclerosing cholangitis 2 were used, 88 of 90 infants were cor-
Progressive familial intrahepatic cholestasis 2 rectly classified into the BA or non-BA
Nonsyndromic biliary hypoplasia 2 group, for an overall accuracy of 98%
Inspissated bile syndrome (with gallbladder agenesis) 1 (Table 4). Two infants were incorrectly
Choledochal cyst 1 classified as having BA; one infant with
histologic features of biliary hypoplasia
* Cystic fibrosis with or without prematurity, sepsis, and parenteral nutrition.
had a sonographically abnormal gall-

848 Radiology: Volume 244: Number 3—September 2007


PEDIATRIC IMAGING: US Diagnosis of Biliary Atresia Humphrey and Stringer

Table 3
bladder wall and no visible CBD, and
one premature, growth-retarded infant US Findings in 90 Infants with Conjugated Hyperbilirubinemia
with neonatal hepatitis syndrome had
Infants in BA Infants in Non-BA
no detectable gallbladder or CBD at US.
Finding* Group (n $ 30) Group (n $ 60) Total (n $ 90)
The mean gallbladder length was
significantly smaller in infants with BA Gallbladder†
(mean # standard deviation, 18.8 Detected 23 58 81
mm # 7.9 [n $ 23]) than in those with- Not seen 7 2 9
out BA (25.9 mm # 6.9 [n $ 58], P " Gallbladder length
.001) (Fig 4). The mean hepatic artery "19 mm 14 9 23
diameter was significantly larger in the !19 mm 9 49 58
Gallbladder shape
BA group than in the non-BA group (2.2
Normal 7 58 65
mm # 0.59 vs 1.6 mm # 0.40, respec-
Abnormal 16 0 16
tively; P " .001) (Fig 5). In contrast,
Gallbladder wall regularity
portal vein diameters were not signifi-
Normal 2 55 57
cantly different between the two groups
Abnormal 21 3 24
(BA group, 4.1 mm # 0.58 [n $ 29]; TC sign
non-BA group, 4.1 mm # 0.59 [n $ 60]; Present 22 0 22
P ! .5), and there were no infants with Absent 8 60 68
reversed blood flow in the portal vein, CBD
an occluded portal vein, or splenic vari- Detected 2 55 57
ces. Only one infant, a boy with BA, had Not seen 28 5 33
an abnormal, coarse liver echotexture. Liver size
In two infants with BA, the CBD was Normal 17 56 73
considered to be visible at US. One of these Enlarged 13 4 17
infants was found at surgery to have a Spleen size
patent distal CBD in continuity with the gall- Normal 19 59 78
bladder but no patent proximal extra- Abnormal 11 1 12
hepatic bile ducts (type 3 BA). Of the four Polysplenia‡
infants with the BA splenic malformation Present 3 0 3
syndrome, three had polysplenia and an in- Absent 27 60 87
terrupted retrohepatic vena cava at US. Inferior vena cava§
Interrupted 5 0 5
The fourth had an absent portal vein, and at
Normal 25 60 85
laparotomy he was found to have a congen-
ital portocaval fistula and a segmented Note.—P " .001 for difference between groups for each finding, except where noted. P values were calculated with the Fisher
spleen. One other infant had an interrupted exact test.
vena cava and BA but no other anomalies at * Findings were evaluated in all 90 infants, except gallbladder length, shape, and wall regularity, which were evaluated in 81
infants because the gallbladder was not visualized in nine infants.
laparotomy. †
P $ .006.
Three infants in the non-BA group had ‡
P $ .035.
cystic fibrosis; two of these infants had a §
P $ .003.
small gallbladder ("19 mm long) and two
had an irregular, thickened gallbladder wall
(Fig 6). In two infants in the non-BA group, limited number of specific US features. used the gallbladder ghost triad (gall-
the gallbladder could not be identified with Using a 7.5-MHz probe in jaundiced in- bladder length " 19 mm, lack of a
US. One infant with no other US evidence fants, Farrant et al (1) determined that smooth mucosal lining with an indistinct
of BA had inspissated bile plug syndrome an absent gallbladder or one with an wall, and irregular or lobular contour)
with agenesis of the gallbladder that was irregular wall or abnormal shape had a in the diagnosis of BA. US examinations
subsequently confirmed at laparotomy. The sensitivity, specificity, and accuracy of were performed with a 5–12-MHz lin-
other also had an absent CBD and was one 90%, 92.4%, and 91.9%, respectively, ear-array transducer in fasting infants.
of the two infants with incorrectly classified in the diagnosis of BA. Diagnostic accu- The gallbladder ghost triad was present
disease described above. racy improved to 95.6% in a subsequent in 30 of 31 infants with BA, with no
study (11) of 158 infants (35 of whom false-positive findings.
had BA) when a 13-MHz linear-array Choi et al (3) evaluated the TC sign
Discussion probe was used. Patients were not fast- in 41 infants and concluded that it was a
Several groups have previously at- ing, and the presence of a TC sign was sensitive marker of BA. BA was con-
tempted to diagnose BA by means of a not recorded. Tan Kendrick et al (4) firmed in 12 of 13 jaundiced infants with

Radiology: Volume 244: Number 3—September 2007 849


PEDIATRIC IMAGING: US Diagnosis of Biliary Atresia Humphrey and Stringer

a positive sign, but one of the 28 infants fants, 25 of whom had BA, and Tan evitable when the presence or absence
with an absent TC sign was mistakenly Kendrick et al (4) identified an identical of the CBD is used as a criterion for
considered to have neonatal hepatitis sensitivity in 31 infants with BA. diagnosing BA, because a patent distal
and was later found to have BA. Other US features of BA have been CBD in continuity with the gallbladder
Whereas some authors (12,13) have evaluated. Azuma et al (16) recorded can be found in 10%–20% of affected in-
promoted the TC sign as a sensitive and the presence or absence of the CBD in fants with type 3 BA (17). Ho et al (8)
specific US marker of BA, others 30 infants, as seen with a 5- or 7-MHz noted that the hepatic artery in children
(4,14,15) have been more cautious. probe. In the 23 infants with confirmed with BA appeared hypertrophied, and
Thus, Park et al (14) found that the TC BA, nonvisualization of the CBD had a others (4) have also commented on the
sign had a sensitivity of 84% and a spec- sensitivity of 83% but a specificity of prominence of the hepatic artery in in-
ificity of 98% in their series of 79 in- only 71%. False-negative results are in- fants with BA.
After a detailed review of previous
Table 4 reports, we evaluated these and other
US features prospectively in a consecu-
Specific US Features as Predictors of BA tive series of infants suspected of having
Sensitivity Specificity Positive Predictive Negative Predictive BA to determine the accuracy of ab-
US Feature (%)* (%)* Value (%) Value (%) dominal US in diagnosis. Although the
frequency of each US feature was signif-
Absent gallbladder 23 (11, 43) 97 (87, 99) 78 72
icantly different between the BA and
Gallbladder " 19 mm 61 (39, 80) 84 (72, 92) 61 84
Abnormal gallbladder shape 70 (47, 86) 100 (92, 100) 100 89
non-BA groups, the variable sensitivity
Irregular gallbladder wall 91 (70, 98) 95 (85, 99) 88 96 and specificity of individual features
TC sign 73 (54, 87) 100 (93, 100) 100 88 noted in the literature were confirmed.
Absent CBD 93 (76, 99) 92 (81, 97) 85 96 Using the criteria proposed by Farrant
Enlarged liver 43 (26, 62) 93 (83, 98) 76 77 et al (11) (irregular gallbladder wall
Abnormal spleen size 37 (21, 56) 98 (89, 100) 92 76 and shape), we obtained an overall
Polysplenia 10 (3, 28) 100 (93, 100) 100 69 diagnostic accuracy of 95%. We agree
Interrupted inferior vena cava 17 (6, 35) 100 (93, 100) 100 71 with Tan Kendrick et al (4) that the
TC sign is a highly specific but less
* Data in parentheses are 95% confidence intervals.
sensitive marker of BA, but we could
not confirm the accuracy of their gall-
bladder ghost triad. Indeed, gallbladder
length was 19 mm or greater in nine of
Figure 4 Figure 5 23 infants (39%) with BA in our series.
In our study, visualization of the
CBD was associated with a sensitivity

Figure 6

Figure 4: Graph shows gallbladder length in Figure 5: Graph shows hepatic artery (HA) Figure 6: Longitudinal sonogram of abnormal
BA and non-BA groups. Mean gallbladder length diameter in BA and non-BA groups. Mean hepatic irregular gallbladder wall (arrow) in 6-week-old
(horizontal lines) was significantly smaller in in- artery diameter (horizontal lines) was significantly infant with cystic fibrosis and conjugated hyperbil-
fants with BA (P " .001). larger in patients with BA (P " .001). irubinemia. This infant did not have BA.

850 Radiology: Volume 244: Number 3—September 2007


PEDIATRIC IMAGING: US Diagnosis of Biliary Atresia Humphrey and Stringer

and specificity of more than 90%, but tempted to determine the interobserver gallbladder ghost triad. Pediatr Radiol 2003;
33:311–315.
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can support the diagnosis of BA. man PC, Quinn CB. Common bile duct in
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