Pediatr Surg Int
DOI 10.1007/s00383-016-3951-9
ORIGINAL ARTICLE
Prognostic values of serum bilirubin at 7th day post-Kasai
for survival with native livers in patients with biliary atresia
Sinobol Chusilp1,2 • Paiboon Sookpotarom1,3 • Kanokan Tepmalai1,4 •
Prapapan Rajatapiti1 • Voranush Chongsrisawat5 • Yong Poovorawan5
Paisarn Vejchapipat1
Accepted: 23 July 2016
Ó Springer-Verlag Berlin Heidelberg 2016
Abstract
Background Biliary atresia (BA) is a serious liver disease
with uncertain prognosis. The objective of this study was to
investigate prognostic values of the [20 % decrease in
serum total bilirubin (TB) at 7th day post-op regarding
early outcome and 5-year survival with native liver in BA.
Methods Biliary atresia patients undergoing Kasai opera-
tion between 2000 and 2014 were reviewed. The ratio of
serum TB at 7th day post-op to pre-op TB levels (TB7/TB0)
was calculated for every patient. TB7/TB0 ratio of \0.8
indicated the [20 % decrease in serum TB. At 6th month
following Kasai operation, outcome of BA patients were
categorized into good outcome (TB \ 2 mg % or clinically
jaundice free) and poor outcome (TB [ 2 mg % or clini-
cally jaundice). For outcome analysis, logistic regression
was used. For survival analysis, Cox regression was applied.
Results There were 133 BA patients (M:F = 68:65)
undergoing Kasai operation. Median age at surgery was
79 days. BA patients with TB7/TB0 ratio of \0.8 were
& Paisarn Vejchapipat
paisarnv@gmail.com
1
Department of Surgery, Faculty of Medicine, Chulalongkorn
University, King Chulalongkorn Memorial Hospital, Thai
Red Cross Society, Rama IV road, Patumwan,
Bangkok 10330, Thailand
2
Department of Surgery, Faculty of Medicine, Khon Kaen
University, Khon Kaen 40002, Thailand
3
Department of Surgery, Panyananthaphikkhu Chonprathan
Medical Center, Srinakharinwirot University, Nonthaburi,
Thailand
4
Department of Surgery, Faculty of Medicine, Chiang Mai
University, Chiang Mai, Thailand
5
Department of Pediatrics, Faculty of Medicine,
Chulalongkorn University, Bangkok 10330, Thailand
•
found in 38 %. Outcome at 6-month post-op could be
evaluated in 126 patients (good: poor = 68:58). The 1-, 3-
and 5-year survival rates with native livers were 85, 70 and
65 %, respectively. The median overall survival with
native livers was 164 months. Median follow-up time was
87 months. Logistic regression showed that gender and age
at operation were not significant factors impacting on early
outcome (p [ 0.05). However, TB7/TB0 ratio of \0.8 was
an independent factor for good outcome (Odds ratio = 3.0,
p = 0.006). Cox regression analysis demonstrated that
5-year survival rate was significantly correlated with TB7/
TB0 ratio of \0.8 (HR = 0.46, 95 % CI 0.23–0.91,
p = 0.025) and outcome at 6th month post-op (HR = 0.05,
95 % CI 0.01–0.15, p \ 0.001).
Conclusions The [20 % decrease in serum TB at 7th day
post-Kasai is a predictor for good outcome. BA patients
with TB7/TB0 of \0.8 had 5-year survival with native
livers significantly higher than those with the ratio of [0.8.
Keywords Biliary atresia
Kasai operation
Serum
bilirubin
Survival rate
Introduction
Biliary atresia (BA) is a serious liver disease that occurs in
infants. It is characterized by obstructive cholangiopathy
affecting both intra- and extrahepatic biliary ducts. Hepatic
porto-enterosotomy or Kasai operation has been accepted
as a standard treatment for decades. However, the prog-
nosis of BA patients who underwent Kasai operation is
uncertain. Although the operation has improved prognosis,
the majority of patients still require liver transplantation
later in their lives [1–4]. There have been a number of
reports to identify predictors of Kasai operation outcome.
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These include age at operation [5, 6], serum bilirubin at
6 weeks after operation [7], serum direct bilirubin (DB)
and aspartate aminotransferase (AST) at 2 months after
Kasai operation [8, 9], repeated cholangitis [10], and AST
to platelet ratio index [11], etc. However, the investigation
of peri-operative serum total bilirubin (TB) as a predictive
marker receives little attention.
The objective of this study was to investigate prognostic
values of the decrease in serum total bilirubin (TB) at 7th
day post-Kasai regarding early outcome and 5-year sur-
vival with native liver in BA. We hypothesize that [20 %
decrease in serum TB within 7 days post-Kasai is associ-
ated with early good outcome and provides better 5-year
survival rate.
Materials and methods
The study was approved by the Institutional Review Board
of the hospital (IRB No. 033/59). The medical charts of BA
patients who underwent Kasai operation at our institution
between 2000 and 2014 were reviewed. Data of gender,
age at Kasai operation, pre-op serum TB (TB0) and serum
TB at 7th day post-op (TB7) were collected. The ratio of
serum TB at 7th day post-op to pre-op TB levels (TB7/
TB0) was calculated for every patient. The TB7/TB0 ratio
of \0.8 indicates that there is [20 % decrease in serum TB
at 7th day following Kasai operation.
At 6th month after Kasai operation, BA patients were
categorized into good outcome (serum TB \ 2 mg % or
clinically jaundice-free) and poor outcome (serum
TB [ 2 mg % or clinically persistent jaundice). For out-
come analysis, binary logistic regression was used. For
survival analysis, log-rank test and cox regression were
applied. The survival with native liver in BA patients was
estimated according to Kaplan–Meier method with end-
points of death or liver transplantation. Survival curves
were compared by log-rank test.
Continuous data are expressed as median and ranges.
Categorical data are expressed as percent (%). p value
of \ 0.05 is regarded as significant difference. SPSS software
version 22 (IBM corp.) was used for all statistical analyses.

Table 1 Patients’ clinical and

Good outcome Poor outcome p value
demographic data based on
(n = 68) group (n = 58)
outcome at 6th month post-
Kasai Gender 0.2872
Male 37 (54.4 %) 26 (44.8 %)
Female 31 (45.6 %) 32 (55.2 %)
Age at operation (days) 78.5 (15–197) 80.5 (21–200) 0.5617
Age at operation \60 days 12 (17.7 %) 11 (19.0 %) 0.8500
TB levels (mg/dl)
Pre-op 10.99 (4.77–25.37) 11.88 (6.00–20.54) 0.4723
7-day post-op 9.49 (3.84–19.86) 12.09 (3.01–25.6) 0.0129
DB levels (mg/dl)
Pre-op 8.71 (2.10–21.09) 8.17 (4.10–15.91) 0.5331
7-day post-op 7.02 (2.10–14.58) 8.36 (1.98–18.34) 0.0037
ALP levels (IU/L)
Pre-op 534 (228–1140) 587 (37–1133) 0.3998
7-day post-op 368 (36–980) 368 (182–889) 0.5953
SGOT levels (IU/L)
Pre-op 212 (85–860) 230 (71–1102) 0.2763
7-day post-op 156 (64–362) 155 (61–354) 0.9232
SGPT levels
Pre-op 162 (40–450) 162 (7–489) 0.9343
7-day post-op 144 (43–385) 143 (3–539) 0.8983
TB7/TB0 ratio of \0.8 33 (49.3 %) 15 (25.9 %) 0.0071
Liver transplantation after Kasai operation 2 (2.9 %) 9 (15.5 %) 0.0125
Duration after Kasai operation (months) 60 (13–107) 20 (9–164) 0.6091
Survival
1-year survival 100 % 78 %
3-year survival 96 % 48 %
5-year survival 96 % 36 %

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Results rate was significantly correlated with TB7/TB0 ratio

of \0.8 (Hazard ratio = 0.46, 95 % CI 0.23–0.91,
There were 133 BA patients (Male: Female = 68:65) who p = 0.025) and outcome at 6th month post-op (Hazard
underwent Kasai operation during the studied period. ratio = 0.05, 95 % CI 0.01–0.15, p \ 0.001).
Median age at surgery was 79 days (range 15–200 days).
BA patients with TB7/TB0 ratio of \0.8 were observed in
38 % (48/126) of the patients. Outcome at 6th month post- Discussion
op could be evaluated in 126 patients (good outcome: poor
outcome = 68:58). Clinical and demographic data of BA Early diagnosis of BA and restoration of bile flow after
patients based on the outcome were shown in Table 1. The Kasai operation have been known to improve the rate of
number of BA patients undergoing Kasai operation each jaundice disappearance in BA patients from 15 to 69 %
year was demonstrated in Fig. 1. [1, 5, 6, 12, 13]. The success of Kasai operation provides a
By using Kaplan–Meier survival analysis, the 1-, 3- and
5-year survival rates with native livers of all BA patients
were estimated at 85, 70 and 65 %, respectively, as shown
in Fig. 2. The median overall survival with native livers
was estimated at 164 months (13.7 years). Median follow-
up time was 87 months. Using log-rank test, BA patients
with TB7/TB0 ratio of \0.8 had 5-year survival with
native liver higher than those with TB7/TB0 of [0.8
(p = 0.0215), as shown in Fig. 3. In addition, BA patients
with good outcome at 6th month after Kasai operation had
5-year survival with native liver higher than those with
poor outcome (p \ 0.001), as shown in Fig. 4.
Logistic regression analysis showed that gender and age
at operation (\60 days) were not significant factors
impacting on early outcome (p [ 0.05). However, TB7/
TB0 ratio of \0.8 was an independent factor for good Fig. 2 Survival curve of 133 BA patients. It shows that 1-, 3- and
outcome (Odds ratio = 3.0, p = 0.006), shown in Table 2. 5-year survival rates with native livers are 85, 70 and 65 %,
Cox regression analysis demonstrated that 5-year survival respectively

Fig. 1 The number of BA patients undergoing Kasai operation during 2000–2014

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The levels of postoperative serum TB have been reported

to suggest the necessity of liver transplantation in early
childhood [15].
Although Kasai operation improves overall survival, the
long-term prognosis is somehow difficult to predict. Sev-
eral studies reported better outcomes when surgery is
performed before 60 days of age and poorer outcomes after
90 days of age [3, 13, 16–18]. Anatomic pattern of BA,
presence of nodular liver appearance at time of Kasai
operation and early postoperative jaundice clearance
(within the first 3 months) are also significant predictors of
survival with native liver [19]. Among all variables, serum
bilirubin post-Kasai operation appears to be a reliable
predictive biomarker for the outcome. An article from the
United States revealed that markedly improved survival
Fig. 3 Survival curve comparisons show that BA patients with TB7/ can be achieved in BA patients with serum TB
TB0 ratio of \0.8 had 5-year survival with native liver higher than
those with TB7/TB0 of [0.8 (p = 0.0215)
level \2 mg % at 3 months after Kasai operation [20].
Reduction in the levels of serum TB from pre-operative
period compared to 6 months post-operative period is an
obvious indicator of clinical outcome [21]. A study from
Germany has shown that serum TB \ 57 lmol/l
(3.33 mg %) at 6 weeks after operation can predict the
success rate of Kasai operation [7].
In our study, only 18 % of the patients received surgical
treatment before 60 days of age. However, BA patients
with age at operation \60 days did not show better prog-
nosis over the patients operated at the older age. This may
be due to the small sample size in one arm of the patients.
Generally, it seems that serum bilirubin levels play an
important role in predicting both success of Kasai opera-
tion and survival rate. Although a lot of reports regarding
roles of serum TB on prognosis in BA have been eluci-
dated, the investigation of proportional decrease in serum
Fig. 4 Survival curve comparisons show that BA patients with good TB within 7 days after surgery as an early predictor for
outcome at 6th month after Kasai operation have 5-year survival with clinical outcome and 5-year survival with native liver in
native liver higher than those with poor outcome (p \ 0.001)
BA patients surprisingly receives little attention.
The present study revealed that serum TB0/TB7 ratio
Table 2 Prognostic factors for good outcome at 6th month post-op of \0.8 is a prognostic marker for good outcome at 6th
Variables Odds ratio 95 % CI p value
month post-Kasai. In addition, the ratio of \0.8 signifi-
cantly correlated with better 5-year survival in BA patients.
Gender 0.61 2.89–1.27 0.185 The TB0/TB7 ratio is a simple and logical predictor for
Age at operation 0.10 0.98–1.01 0.508 outcome in BA. The cut-point of 0.8 was selected because
TB7/TB0 ratio of \0.8 2.98 1.37–6.45 0.006 we thought that 20 % decrease in serum TB within 7 days
([20 % decrease in TB) after Kasai operation is a reasonable level indicating ade-
quate bile flow. Most of all, it is easy to remember and the
calculation of the marker is straightforward. One of the
better chance of a good quality of life without the need of advantages using this marker is that doctors can inform the
liver transplantation [2]. Patients with failed Kasai opera- patients’ parents regarding the probability of the outcome
tion will finally progress to biliary cirrhosis and its fatal within 7 days after surgery and even before discharging the
complications. Inevitably, liver transplantation is the patients from the hospital. Finally, our findings also con-
sequential operation and the last resort [14]. BA patients firmed that jaundice-free status at 6th month post-Kasai is a
with persistent severe jaundice and those with moderate strong prognostic marker for better survival with native
jaundice and bleeding varices require liver transplantation. liver.

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In conclusion, the [20 % decrease in serum TB at 7th
day post-Kasai is a simple marker for predicting the suc-
cess of Kasai operation. In addition, BA patients
with [20 % decrease in serum TB at 7th day post-Kasai
had better 5-year survival with native livers compared to
those with \20 % decrease in serum TB at 7th day post-
Kasai. This marker may be used as an alternative for
prognostic predictor in BA after Kasai operation.
Compliance with ethical standards
Conflict of interest The authors declare that the authors have no
conflict of interest.
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