The Relationship between Clinical Outcomes

After Kasai Operation and Related Factors in Infants

with Biliary Atresia
Mongkol Laohapensang MD, FRCST*,
Patcharaphan Srikuancharoen MD**

* Division of Pediatric Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University,
Bangkok, Thailand
** Department of Surgery, Chaophraya Yommaraj Hospital, Suphanburi, Thailand

Background: Biliary atresia (BA) has unclear etiology, leading to cholestasis and cirrhosis. Kasai portoenterostomy has
been accepted worldwide as the primary treatment for establishing biliary drainage. Successful Kasai operation increases the
survival and reduces the incidence of subsequent liver transplantation. Several prognostic factors have been related to the
results of this procedure.
Objective: To study the relationship between clinical outcomes after Kasai operation and related factors in infants with BA.
Design of study: Retrospective charts review.
Material and Method: The medical data of 48 infants with BA who underwent Kasai operation in the Division of Pediatric
Surgery at Siriraj hospital (from January 1st, 2006 to May 31st, 2015) were retrospectively reviewed. Ten patients were
excluded due to incomplete clinical data. Finally, 38 patients were enrolled in this study. The variables including clinical,
laboratory database, radiologic findings, operative findings, and post-operative conditions were chosen for study.
Results: The median onset of visible jaundice was 4 (0 to 16) weeks of age. The median age at Kasai operation was 82 (34 to
204) days. There were 25 (65.8%) cases who could achieve post-operative jaundice clearance. The incidence of post-
operative cholangitis was 30 (78.9%) cases. The age at the time of Kasai operation had a significant impact on post-operative
jaundice clearance in patients with (p-value = 0.028). The cut-off age, defined by the ROC curve analysis, was 90 days (p-
value = 0.042). Odds ratio for age at the operation of less than or equal to jaundice clearance in patients with 90 days was
4.78 (95% CI 1.13 to 21.32).
Conclusion: The age at the time of Kasai operation has a significant impact jaundice clearance in patients with on the ability
to achieve post-operative jaundice clearance. The patients whose ages at the operation of more than 90 days have a significant
risk for delay clearance of jaundice compared to those of ages less than or equal to 90 days.

Keywords: Biliary atresia, Kasai operation, Portoenterostomy, Age, Outcome

J Med Assoc Thai 2017; 100 (Suppl. 4): S99-S104

Full text. e-Journal: http://www.jmatonline.com
Biliary atresia is a perinatal disease of unclear Kasai portoenterostomy has been accepted
etiology, which is characterized by inflammation and worldwide as the primary surgical treatment for
obliteration of intrahepatic and extrahepatic bile duct, establishing biliary drainage(3). The subsequent liver
leading to cholestasis and cirrhosis. There are several transplantation will be needed because of failure to
levels of obliteration from the porta hepatis to the restore biliary flow after Kasai operation and/or because
opening of the common bile duct into the duodenum. If of decompensated cirrhosis(3). The Kasai operation was
left untreated, biliary atresia will lead to cholestasis, introduced in 1959, and consists of constructing a new
hepatic fibrosis, and development of cirrhosis(1). The bile drainage system, generally by creating an
patients will present with obvious signs of conjugated anastomosis of a Roux-en-Y ascending limb of the
jaundice, pale stool, dark urine, and hepatomegaly(2). jejunum to the porta hepatis region to re-establish a
connection between the intrahepatic bile ducts and
Correspondence to: the intestine. If successful, Kasai operation increases
Laohapensang M, Division of Pediatric Surgery, Department the survival of children with biliary atresia (4) .
of Surgery, Faculty of Medicine Siriraj Hospital, Bangkok 10700,
Thailand.
Nevertheless, the survival of patients with biliary atresia
Phone: +66-2-4198027, Fax: +66-2-4110109 might vary, as several factors were associated with the
E-mail: [email protected] prognosis of biliary atresia(5). Shinkai et al reported

J Med Assoc Thai Vol. 100 Suppl. 4 2017 S99

that the 5-, 10-, and 20-year survival rates of patients count with differentiation, and platelet count), BUN,
with their native livers after Kasai operation were 63%, Creatinine, Liver function test (total bilirubin, direct
54%, and 44%, respectively(3). bilirubin, aspartate aminotransferase (AST), alanine
Several prognostic factors of the Kasai aminotransferase (ALT), alkaline phosphatase (ALP),
operation have been related to the short-term results gamma-glutamyl transpeptidase (GGT), albumin, and
of this procedure. Among them are many that cannot globulin), ultrasonographic findings, findings from
be altered, such as the anatomy of the biliary remnant, intraoperative cholangiography, intra-operative
histology of the liver, portal pressure at the time of findings, use of adjuvant steroid (starting dose at 2
Kasai operation, or association of biliary atresia with mg/kg per day and then reduced by half every week
polysplenia (biliary atresia splenic malformation until completely tapered off), jaundice clearance
syndrome). Other prognostic factors of biliary atresia (defined as total bilirubin <1 mg/dl at post Kasai
are related to the organization of care for these patients, operation), post-operative cholangitis, and the
and therefore are improvable: including the age at necessity of redo-Kasai operation.
Kasai operation, accessibility to liver transplantation,
experience of the center in the management of patients Ethical approval
with biliary atresia(6). Marie-Odile Serinet et al reported This study received the approval of Siriraj
that large series concordantly show that short-term Institutional Review Board.
results of the Kasai operation are better when surgery
is performed early in life. Whether an age threshold Statistical analysis
exists remains unclear(6). Patrick Ho Yu Chung et al also Descriptive statistical analysis was performed
reported that the presence of associated anomaly, using Predictive Analytics Software (SPSS) Statistics
operation with laparoscopic surgery, delayed clearance version 18.0. Results were analyzed using independent-
of jaundice, and repeated cholangitis were associated samples t-test and Mann-Whitney U test for
with adverse outcome, whereas the use of adjuvant continuous variables. The categorical data were
steroid at post-operative period appeared to be analyzed using Pearson Chi-square test and Fisher’s
protective(7). exact test. The cut-off age was defined by receiver-
In the Division of Pediatric Surgery at Siriraj
Hospital, there are patients with biliary atresia who are
Table 1. Demographic data and results
surgically treated with Kasai operation about 2 to 5
cases per year. The aim of this single-center review is
to study about the relationship between clinical Variables n = 38 (%)
outcomes after Kasai operation and related factors in or median
(minimum,
infants with biliary atresia. The result of this study may
maximum)
reveal the improvable or modifiable factors, which could
lead to a better outcome of treatment. Sex
Male 12 (31.6%)
Material and Method Female 26 (68.4%)
A retrospective review of 48 infants with Onset of visible jaundice (weeks) 4 (0, 16)
biliary atresia who underwent conventional Kasai Age at Kasai operation (days) 82 (34, 204)
operation in our institution from January 1st, 2006 to Body weight at operation (kg) 5.3 (3.5, 6.6)
May 31st, 2015 was conducted. Ten patients were Jaundice clearance
Yes 25 (65.8%)
excluded due to incomplete clinical data. Finally, 38
No 13 (34.2%)
patients were enrolled in this study. The diagnosis of Post-operative adjuvant steroid use
biliary atresia was confirmed based on patients’ clinical, Yes 36 (94.7%)
biochemical, radiological, and operative findings. No 2 (5.3%)
The variables including clinical, laboratory Post-operative cholangitis
database, radiologic findings, operative findings, and Yes 30 (78.9%)
post-operative conditions of the patients were chosen No 8 (21.1%)
for study. These were sex, onset of visible jaundice, Redo-Kasai operation
age at operation, body weight at operation, complete Yes 3 (7.9%)
No 35 (92.1%)
blood count (hemoglobin, hematocrit, white blood cell

S100 J Med Assoc Thai Vol. 100 Suppl. 4 2017

operating characteristic (ROC) curve analysis using in 2 cases (15%).
Odds ratio with 95% confidence interval. A p-value of
less than 0.05 was regarded as statistically significant. Discussion
Currently, biliary atresia is still problematic
Results because of the progressive inflammation, hepatic
A total of 48 cases were identified, which 10 fibrosis, and development of liver cirrhosis that would
excluded due to incomplete clinical data. The 38 patients lead to end-stage liver disease or even death if left
were eligible for analysis as demonstrated in Table 1. untreated(5). Identification of prognostic factors related
There were more female than male patients (26: 12). The with outcome after Kasai operation is an important
median onset of visible jaundice was 4 (0 to 16) weeks. question to enable improvements in outcome(7). Kasai
The median age at Kasai operation was 82 (34 to 204) portoenterostomy has been accepted as the primary
days. There were 25 (65.8%) cases who could achieve therapeutic option for establishing biliary drainage.
jaundice clearance after the operation, while the other This operation is still required as the primary treatment
13 (34.2%) cases failed to achieve normal bilirubin level. to avoid liver transplantation because of the shortage
There were 36 (94.7%) cases who received adjuvant of transplant organs, especially for infants, and because
steroid after the operation. The incidence of post- of the morbidity and mortality associated with liver
operative cholangitis was 30 (78.9%) out of 38 cases. transplantation(3). However, it is unknown which factors
Furthermore, there were 3 (7.9%) cases who had the provide clues to patients prognosis. Several studies
necessity of redo-Kasai operation. The median follow- showed that the earlier the surgery, the better the
up time was 17 (2 to 104) months. There were 5 cases outcome(6,8).
who later received a liver transplantation. The outcome of the Kasai operation has been
In patients with biliary atresia who underwent reported to be influenced by various factors such as
Kasai operation, the ability to achieve jaundice the type of BA, age at the initial operation, experience
clearance was defined as a good outcome. Table 2 of the surgical center, era in which surgery was
showed the results of the factors that related to the performed, and postoperative medical care(9). The
ability to achieve good post-operative outcome in our majority of published studies show that the best
study. The age at the time of Kasai operation resulted surgical results are obtained in infants who are 60 to 80
in significant impact on the ability to achieve jaundice days of age at the time of operation(10). Our study
clearance (p-value = 0.028). demonstrated that patients’ age at the time of the Kasai
The cut-off age was defined by the receiver- operation is the significant prognostic factor on the
operating characteristic (ROC) curve analysis (area ability to achieve jaundice clearance after the operation.
under the curve = 0.71, p-value = 0.034). The result The age at the time of operation of less than or equal to
showed that the cut-off age was 90 days (p-value = 90 versus more than 90 days of age resulted in
0.042). Odds ratio for age at the operation less than or significant difference in jaundice clearance. The
equal to 90 days was 4.78 (95% CI 1.13 to 21.32), which patients whose age at the Kasai operation more than
means that the patient who was more than 90 days of 90 days have significant risk for delayed clearance of
age at the operation has 4.78 times of risk for delayed jaundice more than who was less than or equal to 90
jaundice clearance more than who was less than or days of age. However, there were some patients who
equal to 90 days of age. could also achieve jaundice clearance after underwent
Among 25 cases who could achieve jaundice the operation at age more than 90 days. It is concordant
clearance, there were 8 cases (32%) who were more with the result from the study of Davenport et al that
than 90 days of age at the time of the operation. The showed the potential for reasonable medium-term
maximal age at the operation of the jaundice-free patient survival is present in about one third of infants 100
in this study was 162 days. days or older coming to primary corrective surgery(11).
There were 13 cases (34%) who could not This result also supported the use of this procedure,
achieve jaundice clearance. Most patients in this group if possible, even in the older infants. Therefore the
had bilirubin level at 1 and 3 months after the operation operation after 90 days of age is not contraindicated.
lower than the preoperative value. Three of them In some patients who could not achieve
(23%) could live with their native liver (maximal age in jaundice clearance, the level of postoperative bilirubin
this study = 6 years and 5 months). In addition, this level at 1 and 3 months were lower than the preoperative
operation could delay the time for liver transplantation value. Some of them could live with their native

J Med Assoc Thai Vol. 100 Suppl. 4 2017 S101

Table 2. The factors that were related to the ability to achieve jaundice clearance

Variables Jaundice clearance p-value

Yes (n = 25) No (n = 13)

Sex: female 18 (72.0%) 8 (61.5%) 0.714

Onset of visible jaundice (weeks) 3 (0,16) 4 (0, 8) 0.874
Age
Age at Kasai operation (days) 91+36 121+43 0.028
Age <90 days at operation 17 (81%) 4 (19%) 0.042
Body weight at operation (kg) 5.2+0.8 5.5+0.5 0.226
Complete blood count
Hb 10.4+1.1 10.5+1.2 0.963
Hct 31.5+3.2 31.4+3.1 0.984
WBC 14,034+3,949 14,941+4,052 0.510
% Neutrophil 26.5+7.0 30.1+10.1 0.208
% Lymphocyte 60.9+11.5 59.1+12.2 0.194
Platelet 413,000+174,694 355,153+11,003 0.286
BUN 7.2+2.9 5.6+1.5 0.079
Creatinine 0.2+0.7 0.17+0.41 0.055
Liver function test
Total bilirubin 10.2+3.9 2.1+3.6 0.153
Direct bilirubin 7.9+2.7 9.6+2.9 0.072
Aspartate transaminase (AST) 242.7+223.7 332.5+238.9 0.106
Alanine transaminase (ALT) 144.1+93.4 152.4+66.9 0.779
Alkaline phosphatase (ALP) 457.3+164.0 514.2+162.8 0.316
Gamma-glutamyl transpeptidase (GGT) 753.6+345.2 759.2+639.2 0.673
Albumin 3.87+0.49 3.72+0.56 0.389
Globulin 2.16+0.57 2.35+0.48 0.308
Ultrasonographic findings
Presence of gallbladder 11 (44%) 10 (76.9%) 0.034
Presence of atretic gallbladder 8 (72.7%) 3 (30%) 0.086
Presence of triangular cord sign 7 (28%) 1 (7.7%) 0.222
Presence of extrahepatic duct 3 (12%) 2 (15.4%) 1.000
Presence of normal liver parenchyma 24 (96%) 12 (92.3%) 1.000
Intra-operative cholangiography (n = 25)
Presence of gallbladder 3 (23.1%) 6 (66.7%) 0.079
Presence of biliary tree connection 0 (0%) 1 (11.1%) 0.409
Patency of cystic duct 6 (46.2%) 4 (44.4%) 1.000
Patency of common bile duct 3 (23.1%) 4 (44.4%) 0.376
Atresia of porta hepatis 13 (100%) 8 (88.9%) 0.409
Presence of bowel connection 3 (23.1%) 4 (44.4%) 0.376
Intra-operative findings
Normal appearance of the liver 5 (21.7%) 3 (27.3%) 1.000
Presence of ascites 22 (95.7%) 9 (81.8%) 0.239
Patency of cystic duct 2 (8%) 4 (30.8%) 0.154
Patency of common bile duct 2 (8%) 5 (38.5%) 0.034
Presence of fibrous porta hepatis 24 (96%) 11 (84.6%) 0.265
Post-operative adjuvant steroid use 23 (92%) 13 (100%) 0.538
Post-operative cholangitis 19 (76%) 11 (84.6%) 0.609
Redo-Kasai operation 1 (4%) 2 (15.4%) 0.265

liver. Lykavieris et al reported that 23% of the children after the Kasai operation(12). The study of Hartley
survived with their native liver for at least 20 years Jane L. et al showed that transplantation is usually

S102 J Med Assoc Thai Vol. 100 Suppl. 4 2017

indicated within 6 months to 2 years of age in infants What this study adds?
whom bile drainage is not achieved, while about 50% This study demonstrated that patient age at
of the patients who underwent Kasai operation received the time of the Kasai operation is the significant
secondary liver transplantation(13). From our study, few prognostic factor on the ability to achieve jaundice
cases who could not achieve jaundice clearance could clearance after the operation. The patients whose ages
delay the time of liver transplantation. This result at the operation of more than 90 days have significant
indicated that Kasai operation should be done for risk for delayed clearance of jaundice compared to those
bridging before liver transplantation in some cases. with the age of less than or equal to 90 days. However,
In our study, there was an inconsistency of it is possible for the patients in this group to achieve
the statistical significance between the presence of jaundice clearance after the operation. The maximal age
common bile duct from intraoperative cholangiography at operation that could achieve jaundice clearance was
and the patency of common bile duct from 162 days. Therefore Kasai procedure can be use, if
intraoperative findings. It may be resulted from the small possible, even in older infants. Early detection and
sample size of this study. The result of no statistical urgency operation will improve outcome of this
significance in jaundice clearance in post-operative operation.
steroid treatment may derive from the most of the
patients in this study received steroid in post-operative Potential conflicts of interest
period along with small sample size. None.

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 ⌦⌫⌫⌫⌫
⌫ ⌦⌫⌫⌫  ⌫
  ⌫     ⌦⌫        ⌫    
⌦ ⌫  ⌦⌫    ⌫ ⌦⌫ ⌫ ⌦ 
   ⌫  
⌦ ⌫⌫⌫⌫   ⌫     ⌫  
 ⌫   ⌫ ⌫    ⌫  
 ⌫⌫ ⌦⌫  ⌫
⌫⌫
 ⌫    ⌫⌫    ⌫  
  ⌫⌫⌫⌫  

S104 J Med Assoc Thai Vol. 100 Suppl. 4 2017