Research

JAMA Surgery | Original Investigation | PACIFIC COAST SURGICAL ASSOCIATION

Biliary-Enteric Drainage vs Primary Liver Transplant

as Initial Treatment for Children With Biliary Atresia
Elyse LeeVan, MD; Lea Matsuoka, MD; Shu Cao, MS; Susan Groshen, PhD; Sophoclis Alexopoulos, MD

IMPORTANCE Some infants with biliary atresia are treated with primary liver transplant (pLT),
but most are initially treated with biliary-enteric drainage (BED) with a subsequent salvage
liver transplant. Given the improvements in liver transplant outcomes, it is important to
determine whether BED treatment remains the optimal surgical algorithm for patients with
biliary atresia.

OBJECTIVE To compare the survival of patients with biliary atresia initially treated with BED
with patients who underwent pLT.

DESIGN, SETTING, AND PARTICIPANTS This cohort study used deidentified records from the
California Office of Statewide Health Planning and Development database to identify patients
with biliary atresia (n = 1252) between January 1, 1990, through December 31, 2015. Patients
were categorized into 1 of 2 cohorts: those who received BED treatment and those who
underwent pLT. Excluded from the study were those born before January 1, 1995, and those
without any documented operative intervention by age 5 years. Data analysis was performed
from January 1, 1990, to December 31, 2015.

MAIN OUTCOMES AND MEASURES Overall survival was compared between the BED and pLT
cohorts using the Kaplan-Meier method. The treatment’s association with treatment era was
examined by comparing survival before 2002 and on or after January 1, 2002.

RESULTS In total, 1252 patients with biliary atresia were identified. After exclusions, 626
remained; of these patients, 351 (56.1%) were female and 275 (43.9%) were male with a
median (interquartile range) age at intervention for initial BED treatment of 65 (48-81) days.
Among the 626 patients studied, initial BED treatment was performed in 313 patients
(50.0%), and pLT was performed in 313 patients (50.0%). Although patients who underwent
pLT had a higher mortality rate within the first 3 months after the procedure, they had a
reduced risk of long-term mortality compared with patients initially managed with BED
treatment (hazard ratio [HR] ⱖ6 months after the initial procedure, 0.19; 95% CI, 0.08-0.42;
P = .01). Patients requiring salvage liver transplant had a substantially higher risk of mortality
than patients who received pLT (HR, 0.43; 95% CI 0.25-0.76; P = .003). Those who
underwent pLT had superior survival compared with BED treatment recipients on or after
2002 (HR, 0.16; 95% CI, 0.05-0.54; P < .001), and that persisted when censoring patients
who underwent salvage liver transplant (HR, 0.23; 95% CI, 0.07-0.82; P = .01).
Author Affiliations: Department of
Surgery, Huntington Memorial
CONCLUSIONS AND RELEVANCE Patients who underwent pLT experienced superior long-term Hospital, Pasadena, California
survival compared with patients who underwent BED treatment. Multi-institutional trials are (LeeVan); Division of Hepatobiliary
needed to determine which initial treatment is most advantageous to patients with biliary and Liver Transplantation, Vanderbilt
University Medical Center, Nashville,
atresia.
Tennessee (Matsuoka, Alexopoulos);
Department of Preventive Medicine,
Keck Hospital, University of Southern
California, Los Angeles (Cao,
Groshen).
Corresponding Author: Sophoclis
Alexopoulos, MD, Division of
Hepatobiliary and Liver
Transplantation, Vanderbilt
University Medical Center, 1313 21st
Ave S, 801 Oxford House, Nashville,
JAMA Surg. 2019;154(1):26-32. doi:10.1001/jamasurg.2018.3180 TN 37232 (sopho.alexopoulos@
Published online September 12, 2018. vanderbilt.edu).

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 Biliary-Enteric Drainage vs Primary Liver Transplant for Children With Biliary Atresia
B
iliary atresia (BA) is a progressive fibroinflammatory
cholangiopathy of unclear origin affecting 1:10 000 to
1:20 000 live births in the United States.1 Prior to the
availability of liver transplant (LT), surgical biliary-enteric
drainage (BED), most commonly by hepatic portoenteros-
tomy (HPE), was the only therapy that offered the potential
for long-term survival in patients with BA.2 Hepatic portoen-
terostomy was first described in the late 1950s by the pioneer-
ing surgeon Moroi Kasai.3 The procedure involves resection of
the obliterated and fibrotic extrahepatic biliary tree, the hall-
mark of BA, and anastomosis of a segment of small bowel to
the hilar plate, allowing drainage of bile into the intestine.3
Little has changed in the surgical technique of HPE since Ka-
sai’s initial descriptions. Alternative techniques, such as drain-
age using the gallbladder, have been explored but were deter-
mined to have limited application.4
The rate of survival with native liver after a BED treat-
ment is 37.9% to 40% after 5 years and decreases to 25% to
32.1% after 15 years, even at experienced centers and despite
considerable efforts to improve the long-term outcomes.5-7
Mortality occurs secondary to progressive hepatic injury, which
leads to cirrhosis and end-stage liver disease that eventually
require LT in most patients.8 Unfortunately, the poor early ex-
perience and high mortality rate associated with LT relegated
it to a salvage procedure reserved for patients whose BED treat-
ment was unsuccessful.
Advances in the perioperative care, surgical technique, and
immunosuppressive management of the pediatric LT recipi-
ent over the past several decades have markedly improved
short- and long-term outcomes. The current 10-year survival
rate for LT recipients with end-stage liver disease associated
with BA is 90%.9 Most of these LT recipients have undergone
a BED procedure on the recommendation that infants with BA
should receive BED as an initial treatment.1 However, a sub-
set of infants proceed directly to primary LT (pLT).
Using data from a large, statewide database, this study
compared the survival over a 25-year period of infants with BA
initially treated with BED and infants treated with pLT. The
2002 change in liver allocation to a Model for End Stage Liver
Disease/Pediatric End Stage Liver Disease Model (MELD/PELD)–
based system10 was also considered in evaluating whether BED
should remain the initial treatment for BA in the setting of im-
proved pediatric LT outcomes.
Methods
OSHPD Database
This study was approved by the University of Southern Cali-
fornia Institutional Review Board. Informed consent was
waived by the board as the data used in the study were ob-
tained from a state database. Deidentified records of pediat-
ric patients with BA diagnosis (International Classification of
Diseases, Ninth Revision, code 75161) between January 1, 1990,
through December 31, 2015, were requested from the Califor-
nia Office of Statewide Health Planning and Development
(OSHPD). The OSHPD collects data from more than 6000 Cali-
fornia Department of Public Health–licensed health care fa-
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Original Investigation Research
Key Points
Question For infants with biliary atresia, should biliary-enteric
drainage remain the initial treatment of choice and liver transplant
used as salvage therapy?
Findings In this cohort study that included 626 infants with biliary
atresia, patients who underwent primary liver transplant had a
markedly reduced risk of long-term mortality compared with
patients initially managed with biliary-enteric drainage procedure.
Meaning Patients treated with a primary liver transplant live
longer than those initially treated with biliary-enteric drainage;
a multi-institutional clinical trial is necessary to identify the initial
treatment optimal for patients with biliary atresia.
cilities, including 450 hospitals. The OSHPD requires partici-
pating facilities to submit reports on a semiannual basis that
detail patient information subdivided into multiple data cat-
egories on all discharged individuals. Data include admission
and discharge dates; patient age, sex, and primary and sec-
ondary diagnoses; and procedure codes. This information is
then reported annually in patient discharge data. The linked
death file associates patient discharge data via a Social Secu-
rity number and abstract record number to the Death Statis-
tical Master File, a database maintained by the California De-
partment of Public Health that contains death certificate
information.
Patients with BA diagnosis were categorized into 1 of 2 co-
horts on the basis of initial surgical procedure because this rep-
resents the primary treatment decision point: BED (Interna-
tional Classification of Diseases, Ninth Revision, codes 5131, 5132,
5136, 5137, and 5139) or pLT (International Classification of Dis-
eases, Ninth Revision, code 5051 or 5059). Patients in the BED
cohort were further subdivided into those who underwent only
BED procedure (oBD) and those who underwent subsequent
salvage LT (sLT). Patients born before January 1, 1995, and pa-
tients without any documented operative intervention by 5
years of age were excluded from further analysis. Data analy-
sis was performed from January 1, 1990, to December 31, 2015.
Statistical Analysis
Patient demographic and clinical characteristics were sum-
marized and compared among groups using the χ2 test for cat-
egorical factors and the Kruskal-Wallis test for continuous vari-
ables. Overall survival was calculated from the time of first
procedure to the last follow-up; death from any cause was
counted. Patients were censored if they were still alive at the
data-extraction date. Among patients who underwent initial
BED treatment, the likelihood of LT and the likelihood of death
after BED treatment were estimated using the cumulative in-
cidence curve calculations with death or LT, respectively, as
the competing risk event. Overall survival between BED treat-
ment and pLT was compared using Kaplan-Meier curves and
the log-rank test; however, the hazard ratio (HR) was calcu-
lated at a time, starting 6 months (0.5 years) after the initial
procedure to eliminate crossing hazards.
Patients were further categorized into 1 of 2 eras on the ba-
sis of whether the primary procedure was performed before
(Reprinted) JAMA Surgery January 2019 Volume 154, Number 1 27
 Research Original Investigation
Figure 1. Cumulative Incidence of Death and Liver Transplant (LT) Among Patients Who Underwent Biliary-Enteric Drainage (BED) Treatment
A Outcome after BED
0.6
0.5
Cumulative Incidence
0.4
0.3
0.2
0.1
0 0
0 5
Years Since BED
No. at risk
LT 313 131 105
2002 or on or after January 1, 2002. For patients who under-
went BED treatment and patients who underwent pLT, Cox pro-
portional hazard regression, including patient characteris-
tics, was performed to identify significant risk factors for overall
survival. Among patients who underwent initial BED treat-
ment, a test of interaction effect was performed to determine
the association of era and LT with patient survival. For pa-
tients who underwent BED treatment, LT status was defined
as a time-dependent variable, which was assigned as value 1
or 0 at time t measured from BED procedure data, depending
on whether the patient had received LT at that time. Subse-
quent survival analyses were also performed on the basis of
whether the primary procedure was performed before 2002
or on or after January 1, 2002. All P values were based on
2-sided statistical tests at a significance level of .05. The sta-
tistical analysis was performed in SAS, version 9.4 (SAS Insti-
tute Inc), and R, version 3.4.0 (R Foundation for Statistical
Computing).
Results
In total, 1252 patients with BA were identified in the OSHPD
database. Of these patients, 216 (17.3%) were excluded from
further analysis because they were born before 1990. Of the
1036 remaining patients, 410 (39.6%) were excluded from fur-
ther analysis because no operative intervention by age 5 years
exists, because 5-year intervention-free survival is not con-
sistent with the natural history of BA. The remaining 626 pa-
tients were included for analysis; of these patients, 351 (56.1%)
were female and 275 (43.9%) were male with a median (inter-
quartile range [IQR]) age at intervention for initial BED treat-
ment of 65 (48-81) days. An initial BED treatment was per-
formed in 313 patients (50.0%). An sLT was subsequently
performed in 147 (46.9%) of these 313 patients, and the re-
maining 166 (53.0%) did not undergo an sLT. A pLT was per-
formed in 313 patients (50.0%).
At 5 years after BED treatment, the cumulative incidence
of sLT was 45% and death was 5.6% (Figure 1A). Patients who
underwent sLT were significantly older than patients who had
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Biliary-Enteric Drainage vs Primary Liver Transplant for Children With Biliary Atresia
B Outcome after BED before or after 2002
0.6
Before 2002 (LT)
LT 0.5
Cumulative Incidence
After 2002 (LT)
0.4
0.3
0.2
0.1 After 2002 (Death)
Death
Before 2002 (Death)
10 15 0 5 10 15
Years Since BED
No. at risk
70 Before 2002 153 76 73 69
On or after 1/1/2002 160 55 32 1
oBD at the time of diagnosis (median [IQR] age, 66 [49-88] days
vs 57 [43-76] days; P = .001) and at the time of BED treatment
(median [IQR] age, 71 [55-96] days vs 65 [48-81] days; P = .003).
In addition, patients who received sLT had a higher incidence
of cholangitis, sepsis, and bacteremia compared with oBD
patients (Table 1).
The association of initial treatment decision, BED or pLT,
with overall survival was explored. The 1-, 5-, 10-, and 15-year
Kaplan-Meier survival rates (SE) for all patients who received
BED treatment compared with pLT patients were 94% vs 95%,
88% (0.02) vs 94% (0.01), 87% (0.02) vs 91% (0.01), and 85%
(0.02) vs 92% (0.02) (Figure 2A). Although patients who un-
derwent pLT had a higher mortality rate within the first 3
months after the procedure, they had a reduced risk of long-
term mortality compared with patients initially managed with
BED treatment (HR ≥6 months after the initial procedure, 0.19;
95% CI, 0.08-0.42; P = .01).
The association of previous BED treatment with LT was ex-
amined by comparing sLT with pLT. Patients who underwent
pLT were significantly older than patients who underwent sLT
at time of BA diagnosis, but the median (IQR) age at LT did not
differ between pLT and sLT recipients (315 [230-485] days vs
313 [221-505] days; P = .80). Recipients of sLT had higher rates
of infectious complications compared with recipients of pLT
(Table 1). In addition, patients requiring sLT had a substan-
tially higher risk of mortality than patients who received pLT
(HR, 0.43; 95% CI, 0.25-0.76; P = .003) (Figure 2B).
Because of the occurrence of considerable changes to liver
allocation over the course of the study period, we tested for a
difference in survival after LT between the 2 eras (before 2002
and on or after 2002). For patients who underwent initial BED
treatment, a substantial interaction effect was identified be-
tween era and LT, indicating that post-LT survival differed be-
tween the 2 eras (P = .008). Salvage LT was associated with a
substantial increased risk of mortality before 2002 (HR, 9.34;
95% CI, 3.29-26.5; P < .001; Table 2), but this was not the case
for the on-or-after 2002 cohort (HR, 0.99; 95% CI, 0.34-2.91;
P = .98; Table 2). A considerable improvement in survival was
also seen in pLT. Recipients of pLT on or after 2002 had a re-
duced risk of mortality compared with recipients of pLT be-
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 Biliary-Enteric Drainage vs Primary Liver Transplant for Children With Biliary Atresia Original Investigation Research

Table 1. Patient Characteristics Comparison Between Groups

No. (%)
oBD sLT pLT
Variable (n = 166) (n = 147) (n = 313) P Value
Age, median (IQR), d
At diagnosis 57 (43-76) 66 (49-88) 232 (165-358) <.001
At BED 65 (48-81) 71 (55-96) NA .003
At LT NA 313 (221-505) 315 (230-485) .80
BA diagnosis to 1st procedure, median (IQR), d 4 (1-7) 5 (1-8) 41 (1-120) <.001
Sex .23
Male 77 (46.4) 71 (48.3) 127 (40.6)
Female 89 (53.6) 76 (51.7) 186 (59.4)
Procedure era .22
Before 2002 75 (45.2) 78 (53.1) 166 (53.0)
On or after January 1, 2002 91 (54.8) 69 (46.9) 147 (46.9)
Infectious complications Abbreviations: BA, biliary atresia;
Sepsis 6 (3.6) 14 (9.5) 10 (3.2) .01 BED, biliary-enteric drainage;
IQR, interquartile range; LT, liver
Bacteremia 24 (14.5) 44 (29.9) 49 (15.7) <.001 transplant; oBD, only biliary-enteric
Intra-abdominal abscess 3 (1.8) 3 (2.0) 9 (2.9) .73 drainage; pLT, primary liver
transplant; sLT, salvage liver
Cholangitis 95 (57.2) 105 (71.4) 127 (40.6) <.001
transplant.

Figure 2. Association of Initial Treatment With Overall Survival

A Outcome of BED and pLT B Outcome of pLT and sLT

1.0 1.0
Estimated Probability of Survival

Estimated Probability of Survival

pLT
LT pLT
0.9 0.9
BED
sLT
0.8 0.8

0.7 0.7

0.6 0.6

0.5 0.5
0 5 10 15 20 0 5 10 15 20
Years Since Initial Procedure Years Since LT
No. at risk No. at risk
BED 313 242 200 131 67 sLT 147 115 87 53 19
pLT 313 271 211 154 87 pLT 313 271 211 154 87
Survival rate (SE) Survival rate (SE)
BED 1.00 0.88 (0.02) 0.87 (0.02) 0.85 (0.02) 0.84 (0.02) sLT 1.00 0.86 (0.03) 0.85 (0.03) 0.83 (0.03) 0.80 (0.04)
pLT 1.00 0.94 (0.01) 0.93 (0.01) 0.92 (0.02) 0.91 (0.02) pLT 1.00 0.94 (0.01) 0.93 (0.01) 0.92 (0.02) 0.91 (0.02)

A, Patients who received primary liver transplant (pLT) had a higher short-term 0.08-0.42; P = .01). B, Patients who received salvage LT (sLT) had higher
mortality rate after the initial procedure but had lower risk of long-term mortality risk than patients who received pLT (HR, 0.43; 95% CI 0.25-0.76;
mortality than patients who received biliary-enteric drainage (BED) treatment P = .003).
(hazard ratio [HR] ⱖ6 months after the initial procedure, 0.19; 95% CI,

fore 2002 (HR, 0.19; 95% CI, 0.06-0.64; P = .007; Table 2). No ter 2002 persisted when censoring patients who underwent
statistically significant era-associated difference was found in sLT (HR, 0.23; 95% CI, 0.07-0.82; P = .01) (Figure 3C).
the cumulative incidence of sLT (Gray test P = .47) or death
(Gray test P = .08) after BED treatment (Figure 1B).
Next, we compared BED vs pLT by era. No difference was
identified in the Kaplan-Meier survival of patients who re-
Discussion
ceived BED treatment vs pLT before 2002 (Figure 3A). How- Most children with BA in the United States will undergo an ini-
ever, pLT recipients had superior survival compared with BED tial treatment of surgical BED, most frequently by HPE, and
treatment recipients on or after 2002 (HR, 0.16; 95% CI, 0.05- this operation will be unsuccessful in more than 50% of these
0.54; P < .001) (Figure 3B). The superior survival of patients patients 5 years after the intervention. Perioperative risk fac-
who underwent pLT compared with BED treatment on or af- tors for the unsuccessful HPE are well characterized and in-

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 Research Original Investigation Biliary-Enteric Drainage vs Primary Liver Transplant for Children With Biliary Atresia

Table 2. Analysis of Risk Factors for Mortality

Variable Death, No. (%) Hazard Ratio (95% CI) Wald Test P Value
Analysis of Risk Factors for Mortality in BED Before 2002
sLT NA 9.34 (3.29-26.50) <.001
Sex .18
Male (n = 71) 14 (20) 1 [Reference]
Female (n = 82) 10 (12) 0.57 (0.25-1.29)
Age at BED procedure, d .81
≤60 (n = 59) 8 (14) 1 [Reference]
61-90 (n = 61) 11 (18) 1.35 (0.54-3.39)
>90 (n = 33) 5 (15) 1.20 (0.39-3.70)
Days between BA diagnosis and BED treatment .09
≤2 (n = 64) 9 (14) 1 [Reference]
3-7 (n = 53) 5 (9) 0.55 (0.18-1.65)
>7 (n = 36) 10 (28) 1.79 (0.72-4.42)
Analysis of Risk Factors for Mortality in BED On or After January 1, 2002
sLT NA 0.99 (0.34-2.91) .98
Sex .96
Male (n = 77) 9 (12) 1 [Reference]
Female (n = 83) 10 (12) 1.02 (0.42-2.53)
Age at BED procedure, d .86
≤60 (n = 58) 6 (10) 1 [Reference]
61-90 (n = 69) 9 (13) 1.32 (0.46-3.79)
>90 (n = 33) 4 (12) 1.09 (0.29-4.09)
Days between BA diagnosis and BED treatment .59
≤2 (n = 58) 6 (10) 1 [Reference]
3-7 (n = 59) 6 (10 0.89 (0.28-2.79)
>7 (n = 43) 7 (16) 1.53 (0.51-4.61)
Analysis of Risk Factors for Mortality in pLT
Procedure era .007
Before 2002 (n = 166) 21 (12.6) 1 [Reference]
On or after January 1, 2002 (n = 147) 3 (2.0) 0.19 (0.06-0.64)
Sex .53
Male (n = 127) 8 (6.3) 1 [Reference]
Female (n = 186) 16 (8.6) 1.32 (0.56-3.10)
Age at LT procedure, d .36
≤240 (n = 94) 4 (4) 1 [Reference]
241-365 (n = 94) 9 (10) 2.36 (0.72-7.71)
>365 (n = 125) 11 (8.8) 1.86 (0.57-6.02)
Days between BA diagnosis and pLT procedure .42
Abbreviations: BA, biliary atresia;
≤14 (n = 110) 6 (5.5) 1 [Reference] BED, biliary-enteric drainage; LT, liver
15-90 (n = 109) 10 (9.2) 1.93 (0.70-5.35) transplant; NA, not applicable;
pLT, primary liver transplant;
>90 (n = 94) 8 (9) 1.74 (0.59-5.13)
sLT, salvage liver transplant.

clude age at HPE, intrahepatic extension of cholangiopathy,
treatment center experience, and failure of bilirubin levels to
normalize within 3 months.5,8,11,12 Unfortunately, neither the
technique nor the long-term outcomes of BED treatment have
changed in the nearly 70 years since the procedure was first
described.2,5,8 The use of steroids after operation to modu-
late the inflammatory response has also not demonstrated ef-
ficacy, and today the 20-year survival rate of 21% for patients
with their native liver, as described by Altman in 1997, has only
marginally improved.13 In addition, most children who do sur-
vive into adulthood experience severe liver disease. In 2 Eu-
ropean series, 79% to 97% of patients surviving longer than
20 years with their native liver had cirrhosis, and 46% to 69%
had portal hypertension.14,15 The near-universal progression
of fibrosis and cholangiopathy in the native liver of long-term
survivors will certainly necessitate LT as an adult in a large per-
centage of these patients.
Fortunately, LT has developed into a highly effective sal-
vage therapy for those whose BED treatment was unsuccess-
ful. The outcomes have improved year over year, such that
nearly 94% of all children who received LT for the treatment
of BA are alive 1 year after transplant.9 As such, BED func-

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 Biliary-Enteric Drainage vs Primary Liver Transplant for Children With Biliary Atresia Original Investigation Research

tions as a temporizing treatment in most patients. The high fail-

Figure 3. Association of Initial Treatment With Overall Survival by Era
ure rate of BED and the excellent success rate of LT raises the
question of whether it is time for a paradigm change in the treat- A Survival by group before 2002
ment of BA. Specifically, does BED treatment confer a sur- 1.0
vival advantage when compared with pLT?

Estimated Probability of Survival

We used the California OSHPD database to identify all pa- 0.9 pLT

tients with a diagnosis of BA between 1990 and 2015. Pa- BED

0.8
tients were categorized into 2 groups: those initially treated
with BED procedure, regardless of whether they underwent
0.7
sLT, and those who underwent pLT. Patients in the BED co-
hort had a lower early mortality rate, but long-term survival 0.6
was significantly higher among patients in the pLT cohort. We
then examined the association of previous BED treatment with 0.5
0 5 10 15 20
post-LT survival. Salvage LT was found to have an increased Years Since Initial Procedure
risk of death compared with pLT. An explanation for this find- No. at risk
BED 153 134 133 130 67
ing may be the well-documented increased technical diffi- pLT 166 150 149 147 87
culty of LT in the setting of previous hilar dissection and BDE Survival rate (SE)
BED 1.00 0.88 (0.03) 0.87 (0.03) 0.85 (0.03) 0.84 (0.03)
operation. These patients for whom early BED treatment was pLT 1.00 0.90 (0.02) 0.90 (0.02) 0.89 (0.02) 0.87 (0.03)
unsuccessful are at increased risk of infectious complications
and intestinal perforation compared with patients who did not B Survival by group on or after 2002
receive BED treatment, which would be anticipated to ad- 1.0

Estimated Probability of Survival

versely affect outcome.8,16,17 pLT
LT
0.9
A substantial interaction effect was observed in the out-
BED
comes of LT occurring before and on or after January 1, 2002,
0.8
when the MELD/PELD scoring system was implemented. Spe-
cifically, the increased mortality associated with sLT in the pre- 0.7
MELD/PELD era was not observed in the post-MELD/PELD era.
Substantial improvement in survival after pLT was noted. 0.6

These findings are in accordance with continued advances in

0.5
pediatric LT. 17,18 After the implementation of the MELD/ 0 5 10 15
PELD score for allocation, the number of patients receiving de- Years Since Initial Procedure
No. at risk
ceased-donor livers has increased and the pediatric waitlist BED 160 108 67 1
mortality has decreased. In addition, advances in surgical tech- pLT 147 121 62 7
Survival rate (SE)
nique, such as partial liver grafts and live-donor LT, as well as BED 1.00 0.87 (0.03) 0.86 (0.03) 0.86 (0.03)
improvements in the pediatric intensive care for children be- pLT 1.00 0.98 (0.01) 0.98 (0.01) 0.98 (0.01)
fore and after LT have contributed to better outcomes. In ad-
C Survival by group on or after 2002 with sLT censored
dition, prophylaxis recommendations and monitoring for
opportunistic infections as well as the advent of tacrolimus- 1.0
Estimated Probability of Survival

pLT
based immunosuppression, leading to lower rejection rates and LT
0.9 BED
allowing for steroid-sparing protocols, have been instrumen-
tal in the current success of pediatric LT. As anticipated, and 0.8
consistent with other published data, no substantial improve-
ment was noted in the survival of patients who received BED 0.7
treatment between the 2 eras.
0.6

Limitations 0.5
This study is limited by the lack of granularity common to 0 5 10 15
large databases, particularly because the OSHPD database Years Since Procedure
No. at risk
was designed to capture admission, procedure, and discharge BED 160 108 67 1
diagnoses. The fidelity of the data is limited by the quality of pLT 147 121 62 7
Survival rate (SE)
the data entry; more than 410 patients did not have an opera- BED 1.00 0.91 (0.02) 0.90 (0.03) 0.90 (0.03)
tive intervention listed, suggesting missing data or misdiag- pLT 1.00 0.98 (0.01) 0.98 (0.01) 0.98 (0.01)

nosis. Despite this, the OSHPD database provides a valuable

resource that allows the tracking of treatment for a relatively
uncommon disease in a large population over an extended
period.
The OSHPD database, unlike other commonly used surgi-
cal outcomes and transplant databases, allows us to identify
A, No survival difference between patients who received biliary-enteric drainage
(BED) treatment and primary liver transplant (pLT) before 2002. B, Patients who
received pLT had superior survival compared with BED treatment on or after
2002 (HR, 0.16; 95% CI, 0.05-0.54; P < .001). C, Recipients of pLT compared
with BED treatment on or after 2002 persisted when censoring patients who
underwent sLT (HR, 0.23; 95% CI, 0.07-0.82; P = .01).

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 Research Original Investigation Biliary-Enteric Drainage vs Primary Liver Transplant for Children With Biliary Atresia

all patients with a BA diagnosis, regardless of treatment type.
With these data, we were unable to discern the reason that pa-
tients who received pLT were older than their BED counter-
parts or the association of this age difference with overall out-
comes. Furthermore, we were unable to evaluate the individual
factors behind the decision to undergo an initial BED treat-
ment or a pLT, and whether these procedures represent 2 dif-
fering phenotypes of BA as opposed to 1 phenotype treated dif-
ferently. Additional studies will provide answers to these
important questions.
Biliary-enteric drainage with HPE is performed as soon as
possible after the diagnosis of BA, not because of an immedi-
ate risk of mortality but because of a greater risk of an unsuc-
cessful BED procedure associated with increasing age. Most in-
fants with a late diagnosis of BA who do not undergo BED
treatment continue to grow considerably during the first 6 to
12 weeks of life and can undergo LT at a safe weight and with
excellent outcomes. We recognize that the supply of organs
suitable for pediatric LT is limited and demand continues to
outpace supply. However, most patients will require an LT dur-
ing their lifetime, and receiving a transplant at a young age al-
lows for the greater use of left lateral segment grafts from liv-
ing donors without affecting the deceased-donor pool. In
addition, the use of deceased-donor left lateral segment grafts
allows for the transplant of the right trisegments into adults,
thus minimizing the strain on the deceased-donor supply.
Conclusions
The overall findings of this study highlight our responsibility
to address, in a thoughtful and scientifically rigorous man-
ner, the risks associated with unsuccessful BED procedures.
There is, clearly, a subset of patients with BA for whom good
and durable outcomes can be achieved with a Kasai-first ap-
proach. Conversely, a growing number of patients will have su-
perior outcomes with a pLT approach. In the current setting
emphasizing excellent outcomes in pediatric LT, our goal
should no longer be to avoid LT at any cost. The characteris-
tics of patients who would thrive with an initial BED treat-
ment or with pLT need to be elucidated. A prospective, multi-
institutional clinical trial is necessary to determine which initial
treatment will be most advantageous to individual patients
with BA.

ARTICLE INFORMATION
Accepted for Publication: May 17, 2018.
Published Online: September 12, 2018.
doi:10.1001/jamasurg.2018.3180
Author Contributions: Dr Alexopoulos had full
access to all of the data in the study and takes
responsibility for the integrity of the data and the
accuracy of the data analysis.
Concept and design: LeeVan, Groshen, Alexopoulos.
Acquisition, analysis, or interpretation of data: All
authors.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important
intellectual content: All authors.
Statistical analysis: Cao, Groshen.
Administrative, technical, or material support:
Matsuoka, Alexopoulos.
Supervision: Matsuoka, Alexopoulos.
Conflict of Interest Disclosures: None reported.
Meeting Presentation: This paper was presented
at the 89th Annual Meeting of the Pacific Coast
Surgical Association; February 17, 2018; Napa,
California.
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