Biliary drainage surgery before or after 3 months of life versus primary liver transplantation in children with biliary atresia: comparative cohort study

Abstract

Background:
Early biliary drainage surgery (BDS; Kasai) is associated with longer transplant-free survival in biliary atresia. However, evidence is lacking on whether an age limit can be established at which liver transplantation should be performed as first-line treatment for children with a delayed diagnosis of biliary atresia. The aim of the current study was to compare the outcome of a large cohort of children with biliary atresia who underwent BDS after 90 days of life with those who underwent early BDS (before 90 days) and those who did not receive BDS and were directly referred for primary liver transplantation.

Methods:
All patients with biliary atresia treated at Bicêtre, Paris-Saclay University Hospital between 1995 and 2017 were analysed in this STROBE-compliant study. Three groups were defined: BDS before 90 days of life (early BDS); BDS after 90 days of life (late BDS); and patients without BDS who were referred for primary liver transplantation (no BDS). Patient characteristics, overall survival, and native liver survival were compared.

Results:
Of 424 children with biliary atresia, 69 patients (16 per cent) were older than 90 days when they underwent BDS. Twenty-five patients had no BDS and were referred for primary liver transplantation (6 per cent). The main reason for not performing BDS was manifest portal hypertension (18/25). Two- and 5-year transplant-free survival were significantly higher in patients with late BDS compared with no BDS (53.5 versus 12.0 per cent respectively for 2-year data and 30.4 versus 4.0 per cent respectively for 5-year data, P < 0.001). Five- and 10-year overall survival did not differ between early BDS (92 and 91 per cent respectively), late BDS (88 and 83 per cent respectively) and no BDS (80 and 80 per cent respectively, P = 0.061).

Conclusion:
Age alone should not routinely be considered a contraindication to BDS in patients older than 90 days. Liver transplantation in infancy (less than 12 months) could be avoided in 88 per cent of cases with late diagnosis of biliary atresia and is delayed significantly even when BDS is performed after 3 months. Overall survival is at least equal to patients who are referred for primary liver transplantation.

Full text

Biliary drainage surgery before or after 3 months of life
versus primary liver transplantation in children with
biliary atresia: comparative cohort study
Juri Fuchs
1,2,
* , Chaima Mrad
2
, Emmanuel Gonzales
3
, Dior Ndiaye
2
, Virginie Fouquet
2
, Géraldine Héry
2
,
Catherine Baujard
4
, Florent Guérin
2
and Sophie Branchereau
2
1
Department of General, Visceral, Paediatric and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
2
Department of Paediatric Surgery, Paris-Saclay University, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Paris, France
3
Department of Paediatric Hepatology, Paris-Saclay University, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Paris, France
4
Department of Anaesthesiology and Intensive Care, Paris-Saclay University, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Paris, France
*Correspondence to: Juri Fuchs, Department of General, Visceral, Paediatric and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 420,
Heidelberg, 69120, Germany (e-mail: juri.fuchs@med.uni-heidelberg.de)
Parts of the results of this study were presented as a short communication to the Second International Congress on Biliary Atresia and Related Diseases (BARD),
Bruges, Belgium, 18 June 2022.
Abstract
Background: Early biliary drainage surgery (BDS; Kasai) is associated with longer transplant-free survival in biliary atresia. However,
evidence is lacking on whether an age limit can be established at which liver transplantation should be performed as rst-line
treatment for children with a delayed diagnosis of biliary atresia. The aim of the current study was to compare the outcome of a
large cohort of children with biliary atresia who underwent BDS after 90 days of life with those who underwent early BDS (before
90 days) and those who did not receive BDS and were directly referred for primary liver transplantation.
Methods: All patients with biliary atresia treated at Bicêtre, Paris-Saclay University Hospital between 1995 and 2017 were analysed in
this STROBE-compliant study. Three groups were dened: BDS before 90 days of life (early BDS); BDS after 90 days of life (late BDS); and
patients without BDS who were referred for primary liver transplantation (no BDS). Patient characteristics, overall survival, and native
liver survival were compared.
Results: Of 424 children with biliary atresia, 69 patients (16 per cent) were older than 90 days when they underwent BDS. Twenty-ve
patients had no BDS and were referred for primary liver transplantation (6 per cent). The main reason for not performing BDS was
manifest portal hypertension (18/25). Two- and 5-year transplant-free survival were signicantly higher in patients with late BDS
compared with no BDS (53.5 versus 12.0 per cent respectively for 2-year data and 30.4 versus 4.0 per cent respectively for 5-year
data, P<0.001). Five- and 10-year overall survival did not differ between early BDS (92 and 91 per cent respectively), late BDS (88
and 83 per cent respectively) and no BDS (80 and 80 per cent respectively, P=0.061).
Conclusion: Age alone should not routinely be considered a contraindication to BDS in patients older than 90 days. Liver
transplantation in infancy (less than 12 months) could be avoided in 88 per cent of cases with late diagnosis of biliary atresia and is
delayed signicantly even when BDS is performed after 3 months. Overall survival is at least equal to patients who are referred for
primary liver transplantation.
Introduction
Biliary atresia (BA) is a rare neonatal liver disease with
heterogeneous aetiology and clinical evolution and remains fatal if
untreated. While long-term native liver survival can be achieved in
some patients when performing biliary drainage surgery (BDS;
mostly Kasai portoenterostomy (PE)), approximately 80 per cent of
patients born in Western countries require liver transplantation
(LT) when BDS has failed, could not be performed, or other
hepatological complications arise
1
. Young age at diagnosis and
at BDS has been repeatedly shown to be a predictor of better
outcomes, in particular longer native liver survival
2–4
. However,
due to its rarity and the difculty in diagnosing BA, a signicant
proportion of patients are diagnosed late. Previous studies found
that the prognosis for affected infants deteriorates signicantly
at around 3 months of age
2,5
. Given the considerable
improvements in safety and long-term success of paediatric LT,
the question arises of whether BDS should be performed at all in
children with BA older than 90 days
6,7
. Some authors advocate
direct referral for LT as rst-line treatment for these patients,
arguing that previous BDS adds surgical risks and has
ramications for LT
7–9
. Others emphasize the remarkable
success rates of BDS even at older ages and the importance of
prolonging native liver survival in view of persistent organ
shortage for paediatric patients, particularly for infants (less
than 12 months) with a bodyweight of less than 10 kg
5,6,10–12
.
Received: September 18, 2022. Revised: December 12, 2022. Accepted: December 15, 2022
© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which
permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
BJS Open, 2023, zrac175
https://doi.org/10.1093/bjsopen/zrac175
Original Article
Downloaded from https://academic.oup.com/bjsopen/article/7/2/zrac175/7084844 by guest on 25 March 2023

The aim of the current study was to compare the outcome of a
large cohort of children with BA who underwent BDS after 90 days
of life with those who underwent early BDS (before 90 days) and
those who did not receive BDS and were directly referred for
primary LT.
Methods
Ethics
This study was conducted in accordance with the guidelines of the
revised U.N. Declaration of Helsinki in 1975 and its latest
amendment in 2013 (7th revision). In addition, it was approved
by the Commission Nationale de l’Informatique et des Libertés (CNIL;
approval number 1874973).
Study design, patient population, and sample size
calculation
In adherence with the STROBE guidelines
13
, a retrospective,
comparative single-centre cohort study was conducted. All
paediatric patients who were treated for BA at Bicêtre,
Paris-Saclay University Hospital between 1 January 1995 and 31
December 2017 were eligible. Three subgroups were dened as
follows: early BDS, patients with BDS (mostly Kasai PE)
performed before 90 days of life; late BDS, patients with BDS
performed after 90 days of life; and no BDS, patients without
BDS who were referred for primary LT.
Data acquisition, management, and follow-up
Data were extracted from a prospectively maintained database
that is run by a dedicated data management team at the Bicêtre,
Paris-Saclay University Hospital. In addition to those data,
missing information was collected from the medical
administration software of Bicêtre, Paris-Saclay University
Hospital. All patients were included in a standardized follow-up
programme. After discharge, a rst check-up was performed 1
month later. In cases without complications, the next
appointments were performed 3 and 6 months after discharge
and were repeated at 6 months intervals. Closer follow-up with,
in some cases, even weekly appointments, was performed on an
individual basis depending on patient status. The check-ups
consisted of clinical examinations, blood tests, and abdominal
ultrasonography. Additional investigations were performed as
indicated.
Outcome measures and statistical analyses
The main outcome measures of the study were native liver
survival and overall survival, calculated according to the Kaplan
Meier estimates. Additional investigated outcomes were:
postoperative morbidity, with major complications dened as
adverse effects necessitating reoperation or interventions,
corresponding to complications greater than or equal to grade
IIIa according to the Clavien–Dindo classication
14
; success of
BDS, dened as bilirubin levels less than or equal to 20 µmol/l at
6 months of age; and death during the observation interval.
Based on a prospectively maintained Microsoft Excel database,
all statistical analyses were performed with statistical computing
software R
15
. Means were calculated for normally distributed data
and medians for non-normally distributed data. Standard
deviations (s.d.) are given for means and interquartile ranges
(i.q.r.) for medians. The signicance of differences between the
three subgroups were calculated using the ANOVA test for
normally distributed data (followed by a post-hoc Tukey–Kramer
test for multiple comparison), the Kruskal–Wallis test for
non-normally distributed data (followed by a post-hoc Bonferroni
test for multiple comparison), and the chi-squared test or Fisher’s
exact test (if values less than 5) for binary variables. Kaplan–Meier
Table 1 Patient characteristics with preoperative and postoperative data for all three subgroups
Early BDS, n=330 Late BDS, n=69 No BDS, n=25 P
Sex ratio (M : F) 145 : 185 27 : 42 10 : 15 0.729
Premature birth 23 (7.0) 13 (19) 5 (20) 0.002
Late versus no BDS: 0.900
Associated malformation 30 (9.1) 6 (9) 2 (8) 0.980
Age at BDS/diagnosis (days), median (i.q.r.) 53 (31) 107 (32) 126 (80) <0.001
Late versus no BDS: 0.757
Bilirubin at BDS/diagnosis (µmol/l), median
(i.q.r.)
168 (80) 186 (98) 208 (69) 0.009
Late versus no BDS: 0.462
AST at BDS/diagnosis (U/l), median (i.q.r.) 230 (141) 267 (192) 318 (284) 0.004
Late versus no BDS: 0.600
ALT at BDS/diagnosis (U/l), median (i.q.r.) 175 (123) 176 (150) 177 (254) 0.603
Weight at BDS/diagnosis (g), mean(s.d.) 4080(828) 5080(2469) 5560(751) <0.001
Late versus no BDS: <0.001
Postoperative complications after BDS 83 (25.2) 15 (21) n/a 0.549
Major complications 14 (4.2) 5 (7) n/a 0.287
Postoperative mortality after BDS 2 (0.6) 0 n/a 0.970
Alive with native liver at last follow-up 128 (38.8) 18 (26) 0 0.001
Late versus no BDS:
0.003
LT during observation interval 165 (50.0) 41 (59) 20 (80) 0.008
Late versus no BDS: 0.06
Age at rst LT (months), median (i.q.r.) 18 (25) 20 (22) 13 (16) 0.032
Late versus no BDS: 0.016
Deaths during observation interval 33 (10.0)
On LT waiting list: 15
9 (13)
On LT waiting list: 3
5 (20)
On LT waiting list: 4
0.262
Values are n (%) unless otherwise indicated. Kruskal–Wallis test (with post-hoc Bonferroni test) for non-normally distributed data; ANOVA test (with Tukey–Kramer
test) for normally distributed data; chi-squared test/Fisher’s exact test for binary variables. P values refer to comparison between all three subgroups unless
otherwise specied. BDS, biliary drainage surgery; early BDS, BDS before 90 days of life; late BDS, BDS after 90 days of life; AST, aspartate aminotransferase; ALT,
alanine aminotransferase; i.q.r., interquartile range; n/a, not applicable; LT, liver transplantation.
2 | BJS Open, 2023, Vol. 7, No. 2
Downloaded from https://academic.oup.com/bjsopen/article/7/2/zrac175/7084844 by guest on 25 March 2023

curves were calculated for estimating survival with numbers at risk.
These tables were truncated when the number at risk was smaller
than one-third of the starting gure. Differences between groups
were assessed using a two-tailed Mantel–Cox log rank test at a
level of signicance of 5 per cent.
Results
Study population and baseline patient
characteristics
Four hundred and twenty-four patients with BA were treated at
Bicêtre, Paris-Saclay University Hospital in the study interval.
100
Native liver survival of subgroups
75
50
25
0
No BDS versus two others: < 0.001
No BDS versus late BDS: < 0.001
Late BDS versus early BDS: 0.015
12
No. at risk
335 277 192 158 132 115
69 54 34 24 19 16
25 12 4 1 1 1
24 36 48 60
Months after diagnosis
Survival probability (%)
++++++
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
++
++
+++
Native liver survival of subgroups (95% c.i.)
Early BDS 2-year: 60% (55 to 66), 5-year: 47% (42 to 53)
Late BDS 2-year: 53% (43 to 67), 5-year: 30% (21 to 44)
No BDS 2-year: 12% (4 to 35), 5-year: 4% (1 to 27)
P values (log rank test)
Fig. 1 Kaplan–Meier curves for native liver survival of the three subgroups including the numbers at risk and the statistical signicance of the
difference between all three groups tested with a two-tailed Mantel-Cox log rank test at a level of signicance of 5 per cent
BDS, biliary drainage surgery; early BDS, BDS before 90 days of life; late BDS, BDS after 90 days of life.
No. at risk
360 324 284 257 238 220
69 61 58 55 53 49
25 20 19 17 16 15
100
75
50
25
0
Survival probability (%)
+++++++++++++++
++
++
+
++++++++
+
++
++
++
++
++
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
++
++
+
+
+
+
+
+
+++ + + + +
12 24 36 48 60
Months after diagnosis
Overall survival of subgroups (95% c.i.)
Early BDS 2-year: 92% (89 to 95), 5-year: 91% (87 to 94)
Late BDS 2-year: 88% (81 to 96), 5-year: 83% (75 to 93)
No BDS 2-year: 80% (65 to 97), 5-year: 80% (65 to 97)
P values (log rank test)
No BDS versus two others: 0.061
No BDS versus late BDS: 0.730
Late BDS versus early BDS: 0.060
Overall survival of subgroups
Fig. 2 Kaplan–Meier curves for overall survival of the three subgroups including the numbers at risk and the statistical signicance of the difference
between all three groups tested with a two-tailed Mantel-Cox log rank test at a level of signicance of 5 per cent
BDS, biliary drainage surgery; early BDS, BDS before 90 days of life; late BDS, BDS after 90 days of life.
Fuchs et al. | 3
Downloaded from https://academic.oup.com/bjsopen/article/7/2/zrac175/7084844 by guest on 25 March 2023

The early BDS group consisted of 330 patients (78 per cent), the
late BDS group consisted of 69 patients (16 per cent) and the no
BDS group consisted of 25 patients (6 per cent). Late BDS was
performed at a median age of 117 (range 90–198) days. Fifty-four
patients in the late BDS group underwent Kasai PE and 15
patients in this group underwent portocholecystostomy or other
forms of BDS. Two hundred and sixty-seven of the 330 patients
in the early BDS group underwent Kasai PE and 63 patients in
this group underwent portocholecystostomy or other forms of
BDS. See Table 1 for patient characteristics in the two groups of
late BDS and no BDS.
Postoperative course and outcome of late BDS
Overall postoperative 90-day morbidity of late BDS was 21 per cent
(15/69), with major complications occurring in ve patients (7 per
cent), as compared with an overall 90-day morbidity of 25.2 per
cent (86/330) and a rate of major complications of 4.2 per cent
(14/330) in the early BDS group. In the late Kasai group, ve
patients suffered from cholangitis, and six patients suffered from
postoperative ascites. Two patients were reoperated on for bile
leakage, one of them after portocholecystostomy and one after
Kasai PE. In three patients, postoperative ileus due to
intussusception/volvulus indicated surgical revision. Success of
BDS, dened as serum bilirubin below 20 µmol/l at 6 months of
age, was observed in 19 of 69 patients (28 per cent), as compared
with a success rate of 55.2 per cent for early BDS (P=0.001). The
median age of the patients with success of late BDS was 113
(range 90–158) days. Seven patients (11 per cent) had to undergo
LT as infants before turning 12 months. Nine deaths occurred in
the late BDS group during the observation interval: two patients
died of sepsis and eventual multiple organ failure after
re-transplantation; three patients with associated malformations
died before listing due to cardiac failure; one patient died of
meningitis not associated with BA before listing; and three
patients died while being on the waiting list (two of hepatorenal
syndrome and one of liver failure). At 2 years, 34 patients in the
late BDS group were alive and not transplanted (49 per cent).
Eighteen children (26 per cent) were alive with their native liver
at last median follow-up of 97 (range 13–185) months.
Reasons for not performing BDS
In the no BDS group, 18 of 25 patients had manifest portal
hypertension and thus did not undergo BDS. In 14 of those 18
patients, diagnosis of portal hypertension was made by
ultrasonography. Criteria for diagnosis of portal hypertension
via ultrasonography were visible collateral veins in the hepatic
hilum, and/or an increased stiffness of the liver and spleen. In
four patients, explorative laparotomy revealed visible collateral
veins in the hepatic hilum as clear signs of manifest portal
hypertension, and no BDS was performed. In four of the 25
patients, advanced age at diagnosis of BA (greater than or equal
to 6 months) was the reason for not performing BDS. In one case,
co-morbidities contraindicated early surgery, and in one other
case the reason was unknown. Five deaths occurred in the no
BDS group during the observation interval: one patient with
associated malformations died of cardiac failure before being
listed for LT; and four patients died while being on the waiting
list (one of liver failure and three of hepatorenal syndrome).
Comparison of native liver and overall survival
The median follow-up of the whole patient cohort was 90 (mean
99, range 1–293) months. Six patients in the late BDS group and
three patients in the no BDS group were lost to follow-up
between 1 and 60 months after diagnosis (median 10 months).
Thirty patients in the early BDS group were lost to follow-up
after a median of 15 (range 1–37) months. Two- and 5-year
native liver survival among the entire cohort of 424 patients
were 57 per cent (95 per cent c.i. 52 to 62 per cent) and 42 per
cent (95 per cent c.i. 37 to 47 per cent) respectively. Native liver
survival differed signicantly among the subgroups (no BDS
versus late BDS: P<0.001, no BDS versus early BDS: P<0.001, late
BDS versus early BDS: P=0.015, see Fig. 1). Whereas patients
undergoing late BDS had 2- and 5-year native liver survival of 53
per cent (95 per cent c.i. 43 to 67 per cent) and 30 per cent (95
per cent c.i. 21 to 44 per cent) respectively, patients without BDS
had native liver survival of 12 per cent (95 per cent c.i. 4 to 35
per cent) at 2 years, and 4 per cent (95 per cent c.i. 1 to 27 per
cent) at 5 years. In comparison, patients undergoing BDS before
90 days had native liver survival of 60 per cent (95 per cent c.i.
55 to 66 per cent) and 47 per cent (95 per cent c.i. 42 to 53 per
cent) at 2 and 5 years respectively (Fig. 2).
Overall survival was not signicantly different across the three
subgroups, as shown in Fig. 2. However, a trend towards better
survival in patients undergoing early BDS was observed,
followed by the group of patients with late BDS. Patients without
BDS had the lowest 2- and 5-year survival (Fig. 2).
Discussion
Sixteen percent of all patients diagnosed with BA in the authors’
tertiary care centre underwent late BDS (greater than 90 days of
age). This rate of patients operated on after 90 days is within the
range of previous studies that reported on late Kasai procedures
in children older than 3 months
5,6,16,17
. The success rate
regarding bilirubin clearance of patients with late BDS (28 per
cent) in this cohort was signicantly lower than in patients with
BDS before 90 days of age (55 per cent). This is in line with
numerous previous studies, which showed adverse effects of
older age at the time of BDS in children with BA
1,2,5,6,18
. On the
other hand, several studies reported encouraging success rates
in patients undergoing late BDS of up to 55 per cent
16
and 5-year
native liver survival of up to 45 per cent
5
. In this series, the
success rate of late BDS was 28 per cent, hence similar to results
of other large cohort studies
6,16
. For 88 per cent of the patients
undergoing late BDS, LT in infancy could be avoided. More than
half of the children in this series who underwent late BDS were
alive with their native liver after 2 years, 30 per cent still after 5
years. These results conrm the potential to delay LT in patients
with BA even when BDS is performed late. In view of persisting
organ shortage, in particular for very small infants with a
bodyweight of less than 10 kg, prolongation of native liver survival
is highly desirable
11,12
. Moreover, many studies indicated a worse
outcome of LT in children with BA under the age of 12 months
19–21
,
which reinforces the need for delaying LT and emphasizes the
importance of BDS in children aged 3 months or older.
Ninety days has been repeatedly dened as an important
threshold in the surgical treatment of children with BA
5,6,22
.
Several multicentre or registry studies suggested that the
prognosis for native liver survival is signicantly worse in
patients undergoing BDS after 3 months of life
2,6,23
. However,
other large cohort studies did not conrm these ndings and no
correlation between age at Kasai and postoperative bilirubin
clearance was found
24–28
. The association of age at BDS and
short- as well as long-term outcome in BA does not seem to be
linear
24
. Accordingly, long-term native liver survival has been
previously reported in children who were older than 90 days at
4 | BJS Open, 2023, Vol. 7, No. 2
Downloaded from https://academic.oup.com/bjsopen/article/7/2/zrac175/7084844 by guest on 25 March 2023

the time BDS was performed
17,23,24
. As reported by other studies,
long-term native liver survival was achieved in several patients,
even when they were operated after 120 days of life also in this
series. This nding further strengthens the indication of BDS
after 3 months of life. The direct perioperative risks of BDS in
general, and late BDS in particular, are low, as shown by a
postoperative mortality rate of 0 per cent and a major
complication rate of 7 per cent in the current cohort. Within
the subgroup of late BDS, there was no tendency towards
worse outcome with increasing age, a nding that further
questions age as a single decisive factor in those patients. At
the same time, BDS did not seem to have negative
consequences for possible consecutive LT, which is mirrored by
the superior overall survival of patients with late BDS
compared with those with no BDS in this study. While there are
contradictory results concerning the ramications of BDS on
surgical risks of LT and post-transplant outcome in children
with BA
7,8
, recent studies on the impact of previous Kasai
operation versus primary LT concluded that post-LT outcome is
at least equal in those two groups, with a signicantly higher
age at LT in the Kasai group
9,12
. The authors’ ndings reveal
that age alone should probably not be a criterion to decide
against BDS and that other factors must be taken into account,
some of which might not have been identied yet.
This study has several limitations, including the
retrospective, non-randomized design. However, it should be
evaluated in the context of a rare paediatric condition with
small patient numbers, where evidence from RCTs is lacking
and retrospective trials are an invaluable resource to generate
evidence. Moreover, the two groups of late BDS and no BDS
were not matched because of the limited sample size and
therefore inevitably exhibit baseline differences. Although
preoperative bilirubin and liver aminotransferase levels did
not differ signicantly between the late BDS and no BDS
subgroups, the high percentage of manifest portal
hypertension in the no BDS group may hint at more advanced
stages of disease in these children compared with the late BDS
group, which in turn would weaken the comparability of
long-term outcomes. A major strength of this study is the
comparatively large number of patients, and, to the best of the
authors’ knowledge, it is the largest single-centre series of
patients undergoing late BDS. This allowed for a meaningful
comparative study of contemporary subgroups. Moreover, BA
patients are treated from rst diagnostics to potential LT
including long-term follow-up at the authors’ institution, and
one specialized dedicated surgical team performs BDS as well
as paediatric LT. As a consequence, care of these patients
remains in one hand, and bias towards one approach is
strongly reduced in this study, as there is no personal or
institutional interest in advocating either late BDS or primary
LT in patients with a delayed diagnosis of BA.
These results support the recommendation to also consider
BDS in patients older than 90 days. Although the indication
for surgery in these patients must be thoroughly assessed
and remains an individual decision, advanced infant age
alone is not an appropriate criterion to deny these patients
BDS and thus the chance of long-term native liver survival.
Future studies should investigate additional factors that
predict the outcome of patients with late diagnosis of BA
to advance towards an individually tailored therapy. In
addition, the impact of late BDS on intraoperative and
postoperative complications of secondary LT should be
further investigated.
Funding
The authors have no funding to declare.
Acknowledgements
The authors thank the team of the coordinating national
reference centre for biliary atresia at Bicêtre, Paris-Saclay
University Hospital and by name Amaria Remil, Thi-Hanh
Seguin, and Thanh-Nga Nguyen, for their great work in data
acquisition and management. Moreover, the authors thank all
participating patients, their parents, and their carers.
Disclosure
The authors declare no conict of interest.
Data availability
The datasets used and/or analysed during the current study are
available from the corresponding author upon reasonable
request.
References
1. Fanna M, Masson G, Capito C, Girard M, Guerin F, Hermeziu B
et al. Management of biliary atresia in France 1986 to 2015:
long-term results. J Pediatr Gastroenterol Nutr 2019;69:416–424
2. Serinet M-O, Wildhaber BE, Broue P, Lachaux A, Sarles J,
Jacquemin E et al. Impact of age at Kasai operation on its
results in late childhood and adolescence: a rational basis for
biliary atresia screening. Pediatrics 2009;123:1280–1286
3. Okubo R, Nio M, Sasaki H, Society JBA. Impacts of early Kasai
portoenterostomy on short-term and long-term outcomes of
biliary tresia. Hepatol Commun 2021;5:234–243
4. Davenport M, Caponcelli E, Livesey E, Hadzic N, Howard E.
Surgical outcome in biliary atresia: etiology affects the
inuence of age at surgery. Ann Surg 2008;247:694–698
5. Davenport M, Puricelli V, Farrant P, Hadzic N, Mieli-Vergani G,
Portmann B et al. The outcome of the older (≥100 days) infant
with biliary atresia. J Pediatr Surg 2004;39:575–581
6. Chardot C, Carton M, Spire-Bendelac N, Le Pommelet C,
Golmard J-L, Reding R et al. Is the Kasai operation still
indicated in children older than 3 months diagnosed with
biliary atresia? J Pediatr 2001;138:224–228
7. Superina R. Biliary atresia and liver transplantation: results and
thoughts for primary liver transplantation in select patients.
Pediatr Surg Int 2017;33:1297–1304
8. Alexopoulos SP, Merrill M, Kin C, Matsuoka L, Dorey F,
Concepcion W et al. The impact of hepatic portoenterostomy
on liver transplantation for the treatment of biliary atresia:
early failure adversely affects outcome. Pediatr Transplant 2012;
16:373–378
9. Lemoine CP, LeShock JP, Brandt KA, Superina R. Primary liver
transplantation vs. transplant after Kasai portoenterostomy
for infants with biliary atresia. J Clin Med 2022;11:3012
10. Uecker M, Kuebler JF, Schukfeh N, Pster ED, Baumann U,
Petersen C et al. Kasai procedure in patients older than 90
days: worth a cut. Eur J Pediatr Surg 2022;32:80–84
11. Neto JS, Feier FH, Bierrenbach AL, Toscano CM, Fonseca EA,
Pugliese R et al. Impact of Kasai portoenterostomy on liver
transplantation outcomes: a retrospective cohort study of 347
children with biliary atresia. Liver Transpl 2015;21:922–927
Fuchs et al. | 5
Downloaded from https://academic.oup.com/bjsopen/article/7/2/zrac175/7084844 by guest on 25 March 2023

12. Yoeli D, Choudhury RA, Sundaram SS, Mack CL, Roach JP,
Karrer FM et al. Primary vs. salvage liver transplantation for
biliary atresia: a retrospective cohort study. J Pediatr Surg 2022;
57:407–413
13. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC,
Vandenbroucke JP et al. The Strengthening the Reporting of
Observational Studies in Epidemiology (STROBE) statement:
guidelines for reporting observational studies. Int J Surg 2014;
12:1495–1499
14. Dindo D, Demartines N, Clavien PA. Classication of surgical
complications: a new proposal with evaluation in a cohort
of 6336 patients and results of a survey. Ann Surg 2004;240:205–213
15. R Core Team. R: A Language and Environment for Statistical Computing.
Vienna, Austria: R Foundation for Statistical Computing, 2021
16. Wong K, Chung P, Chan I, Lan L, Tam P. Performing Kasai
portoenterostomy beyond 60 days of life is not necessarily
associated with a worse outcome. J Pediatr Gastroenterol Nutr
2010;51:631–634
17. Ramachandran P, Safwan M, Tamizhvanan V, Balaji MS,
Unny AK, Vij M et al. Age is not a criterion in patient selection
for Kasai portoenterostomy. J Indian Assoc Pediatr Surg 2019;
24:271
18. Altman RP, Lilly JR, Greenfeld J, Weinberg A, van Leeuwen K,
Flanigan L. A multivariable risk factor analysis of the
portoenterostomy (Kasai) procedure for biliary atresia: twenty-
ve years of experience from two centers. Ann Surg 1997;226:
348–353
19. Fouquet V, Alves A, Branchereau S, Grabar S, Debray D,
Jacquemin E et al. Long-term outcome of pediatric liver
transplantation for biliary atresia: a 10-year follow-up in a
single center. Liver Transpl 2005;11:152–160
20. Barshes NR, Lee TC, Balkrishnan R, Karpen SJ, Carter BA, Goss
JA. Orthotopic liver transplantation for biliary atresia: the
U. S. experience. Liver Transpl 2005;11:1193–1200
21. Arnon R, Annunziato RA, D’Amelio G, Chu J, Shneider BL. Liver
transplantation for biliary atresia: is there a difference in
outcome for infants? J Pediatr Gastroenterol Nutr 2016;62:220–225
22. Nio M, Wada M, Sasaki H, Tanaka H. Effects of age at Kasai
portoenterostomy on the surgical outcome: a review of the
literature. Surg Today 2015;45:813–818
23. Lykavieris P, Chardot C, Sokhn M, Gauthier F, Valayer J, Bernard
O. Outcome in adulthood of biliary atresia: a study of 63 patients
who survived for over 20 years with their native liver. Hepatology
2005;41:366–371
24. Shinkai M, Ohhama Y, Take H, Kitagawa N, Kudo H, Mochizuki K
et al. Long-term outcome of children with biliary atresia who
were not transplanted after the Kasai operation: >20-year
experience at a children’s hospital. J Pediatr Gastroenterol Nutr
2009;48:443–450
25. Leonhardt J, Kuebler J, Leute P, Turowski C, Becker T, Pster E-D
et al. Biliary atresia: lessons learned from the voluntary German
registry. Eur J Pediatr Surg 2011;21:82–87
26. Schneider, Brown M., Haber B., Whitington P.F., Schwarz K.,
Squires R et al. Biliary Atresia Research Consortium. A
multicenter study of the outcome of biliary atresia in the
United States, 1997 to 2000. J Pediatr 2006 148:467–474
27. Wildhaber BE, Coran AG, Drongowski RA, Hirschl RB, Geiger JD,
Lelli JL et al. The Kasai portoenterostomy for biliary atresia: a
review of a 27-year experience with 81 patients. J Pediatr Surg
2003;38:1480–1485
28. McKiernan PJ, Baker AJ, Kelly DA. The frequency and outcome of
biliary atresia in the UK and Ireland. Lancet 2000;355:25–29
6 | BJS Open, 2023, Vol. 7, No. 2
Downloaded from https://academic.oup.com/bjsopen/article/7/2/zrac175/7084844 by guest on 25 March 2023