ORIGINAL ARTICLE

Biliary Atresia in Infants with Cholestasis

Budi Purnomo*, Badriul Hegar**
* Department of Child Health, Harapan Kita Women and Children Hospital, Jakarta
** Department of Child Health, Faculty of Medicine
Dr. Cipto Mangunkusumo General National Hospital, Jakarta

ABSTRACT
Background: Cholestasis is a pathological condition due to impaired secretion and excretion of bile into
the duodenum. The etiology should be found within golden period age (< 10 weeks of life) in order to get
better outcome. Biliary atresia is characterized by total obstruction of extrahepatic biliary system. The cause
is unknown. The only effective treatment is Kasai procedure, which should be done at 8 weeks age or less. The
aim of this study was to observe the pattern of cholestasis cases in infants.
Method: A descriptive study was conducted on 63 patients with cholestasis at the Harapan Kita Woman and
Children Hospital, Jakarta between January 2008 and December 2009. Data was obtained from the computerized
medical record database system. Statistical analysis was performed using SPSS program.
Results: There were 63 infants, include of 40 (63.5%) boys. Age at admission were 80.2 (30-207) days. The
laboratory findings included mean serum levels of hemoglobin 8.9 g/dL, conjugated bilirubin 12 mg/dL, alanine
transaminase 149 u/L, aspartate transaminase 236 u/L, alkaline phospatase 582 u/L and gamma-glutamyl
transpeptidase level 326 u/L. Biliary atresia was diagnosed in 8 (12.7%) infants by abdominal ultrasonography
examination, cholangiography and liver biopsy. Kasai procedure (portoenterostomy) was performed to all those
infants. Two of those infants died.
Conclusion: Cholestasis has become one of the most common problem found in infants. Biliary atresia
should always be considered as one of the cause, since early diagnosis and immediate treatment are needed to
provide a good outcome.

Keywords: cholestasis, biliary atresia, Kasai procedure

ABSTRAK
Latar belakang: Kolestasis adalah suatu kondisi patologis akibat gangguan sekresi dan ekskresi empedu ke
duodenum. Etiologi penyakit ini sebaiknya ditemukan pada usia < 10 minggu kehidupan untuk mendapatkan hasil
yang lebih baik. Atresia bilier ditandai dengan obstruksi total sistem ekstrahepatik empedu dengan penyebab
yang belum diketahui. Satu-satunya pengobatan yang efektif pada saat ini yaitu dengan prosedur Kasai yang
sebaiknya dilakukan pada usia 8 minggu atau kurang. Penelitian ini bertujuan untuk melihat gambaran pola
kasus kolestasis pada bayi.
Metode: Penelitian deskriptif dilakukan pada 63 pasien bayi dengan kolestasis di Rumah Sakit Anak dan Bunda
Harapan Kita, Jakarta selama bulan Januari 2008-Desember 2009. Data diperoleh dari sistem komputerisasi
rekam medis pasien. Analisis statistik dilakukan dengan program SPSS.
Hasil: Didapatkan 63 pasien bayi yang terdiri dari 40 (63,5%) bayi laki-laki. Rata-rata usia pasien saat
masuk rumah sakit adalah 80,2 hari (30-207). Pada hasil laboratorium ditemukan rerata kadar hemoglobin
darah 8,9 g/dL, bilirubin direk 12 mg/dL, alanin aminotransferase (ALT) 149 u/L, aspartat transaminase (AST)
236 u/L, alkali fosfatase 582 u/L dan rerata kadar gamma-glutamil transpeptidase 326 u/L. Atresia bilier
didiagnosis pada 8 (12,7%) bayi dengan pemeriksaan ultrasonografi abdomen, kolangiografi dan biopsi hati.
Prosedur Kasai (portoenterostomi) dilakukan pada semua bayi tersebut, namun terdapat dua bayi meninggal.

160 The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy

 Biliary Atresia in Infants with Cholestasis

Kesimpulan: Kolestasis telah menjadi salah satu masalah yang paling sering ditemukan pada bayi. Atresia
bilier dapat dipertimbangkan sebagai salah satu penyebabnya, untuk itu diperlukan diagnosis dini dan pengobatan
segera agar memberikan hasil yang baik.

Kata kunci: kolestasis, atresia bilier, prosedur Kasai

INTRODUCTION
data about the subjects was obtained from computerized
Cholestasis is a pathological condition due to database system of medical record unit including age,
impaired secretion and excretion of bile into the sex, hemoglobin level, serum levels of conjugated
duodenum. Clinically, the infants will have yellow billirubin, alanine aminotransferase (ALT), aspartate
discoloration of the skin, enlarged liver, pale stools transaminase (AST), alkaline phospatase (ALP),
and dark urine. The laboratory tests show conjugated gamma-glutamyl transpeptidase (GGT), abdominal
bilirubin level of > 1 mg/dL in total bilirubin level ultrasound, cholangiography, liver biopsy, and Kasai
< 5 mg/dL or conjugated bilirubin of > 20% of the total procedure. Statistical analysis was performed by SPSS.
bilirubin > 5 mg/dL.1 The etiologies of cholestasis are
divided into extra and intrahepatic and each has specific RESULTS
etiology. Intrahepatic cholestasis is characterized by Patients were mostly boys (63.5%) with an average
hepatocyte dysfunction and impaired patency of the age of 2.5 months. They had been suffered from anemia
extrahepatic biliary system, while the extrahepatic with mean hemoglobin levels less than 10 g/dL and
neonatal cholestasis is characterized by complete and conjugated bilirubin levels over 10 mg/dL. The mean
persistent cholestasis.2 serum levels of ALT and AST increased less than 10
Infants with such clinical symptoms require further times of the normal value (Table 1).
diagnostic evaluations since infants with conjugated Table 1. Patient characteristics
hyperbilirubinemia is always abnormal and should be Characteristic Results
considered to have a liver dysfunction. Biliary atresia Age (days) 80.2 (1-207)
is the most common causes extrahepatic cholestasis in Sex (%)
Boy 40 (63.5)
infants. The incidence has been reported to vary from Girl 23 (36.5)
1 : 10,000 to 1 : 15,000 live birth.2 Infants may have Laboratory findings
Hemoglobin (g/dL) 8.9 (6-14.4)
good clinical condition with white stool more than 7 Conjugated bilirubin (mg/dL) 12 (10-23)
days, hepatomegaly with no splenomegaly, and the ALT (u/L) 149 (13-454)
bilirubin level is not always very high. Biliary atresia AST (u/L) 236 (24-850)
ALP (u/L) 582(102-1,459)
is an emergency condition that requires immediate GGT (u/L) 326 (16-2,530)
surgery intervention.1 ALT: alanine aminotransferase; AST: aspartate transaminase; ALP: alkaline
phospatase; GGT: gamma-glutamyl transpeptidase
Prognosis of biliary atresia depends on several
factors. Kasai procedure performed before 6 weeks All had undergone ultrasound examination and 8
of age infants would give 80% probability of 5-year (12.7%) of them had presentation suggestive of biliary
jaundice-free survival rate.1 Overall, the 10-year atresia. All those eight infants had also been undergone
survival rate is 90%. Failures of Kasai procedure are the cholangiography, liver biopsy and followed by
influenced by control of nutrition (nutrition, vitamins) Kasai procedure (Table 2).
and timely liver transplantation.2 Many infants with
cholestasis have been hospitalized in women and Table 2. Diagnostic and Kasai procedure
Type of diagnostic procedure n
children hospital; therefore, this study aimed to observe
Ultrasonography abdomen (n = 63)
the pattern of infant cholestasis cases in Harapan Kita Atresia biler 8
Women and Children Hospital. Sludge (bile plaque syndrome) 48
Hepatitis 7
Cholangiography (n = 8)
METHOD Confirmed biliary atresia 8
Liver biopsy (n = 8)
The present study was a descriptive study conducted Confirmed biliary atresia 8
in 63 infants who had been diagnosed with cholestasis Kasai procedure (n = 8)
Died after several times of control 2
at the Harapan Kita Woman and Children Hospital, Lost of contact after several time of control 4
Jakarta between January 2008 and December 2009. The Could not be traced 2

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Budi Purnomo, Badriul Hegar

DISCUSSION USG was performed in two-phase procedure. The first

Bilirubin is the final catabolism product of phase was done after 12-hour fasting and the second
erythrocytes. Bilirubin is bound by albumin and phase was completed in 2 hours after giving breast
transferred to the liver, which subsequently being milk or formula milk. The presence of the triangular
conjugated with glucoronic acid to form conjugated cord sign above the portal vein bifurcation could
bilirubin.3 A condition of jaundice with direct bilirubin be a sensitive radiologic marker for biliary atresia.9
serum level more than 50% of total bilirubin is defined Abdominal ultrasound has some advantages since it
as conjugated hyperbilirubinemia. Such condition carries minimal risk and no time delay. Experts in
can be caused by intrahepatic (45%) or extrahepatic ultrasound examination could point to biliary atresia
(5%) or intra and extrahepatic (45%) cholestasis. by demonstrating an irregularly shaped or absent gall
Hyperbilirubinemia of intrahepatic cholestasis occurs bladder.10 Eight infants (12.7%) in this study were
when there is a blockage of the bile flow or hepatocyte diagnosed on ultrasound as biliary atresia.
excretion transport failure of bile duct obstruction.4 Cholangiography followed by liver biopsy and
After birth, the clinical triad of biliary atresia Kasai procedure are mandatory in biliary atresia
are jaundice, alcoholic stool and dark urine, and infants. Biliary atresia could be diagnosed by
hepatomegaly. The general condition of the child is histopathologic examination at the age of 4-7 weeks.2
usually good. There is no failure to thrive, at least in Edema or expanded portal tracts, bile duct damage
the first month of life. Jaundice at two weeks of life and reduplication, as well as fibrosis are strongly
is relatively common (up to 15%), however it is not suggested a large bile duct obstruction, which biliary
always associated with liver disease. Jaundice infants atresia is the most common cause.11 Percutaneous liver
with dark urine (conjugated /direct bilirubin) are biopsy is a reliable, definitive, and safety technique.
always abnormal. Normal prothrombin time (PT) after Experienced pathologist may yield diagnosis in 90-95%
giving parenteral vitamin K is considered as cholestasis of cases.12 In this study, 8 infants had suggestive results
or abnormality in bile formation or excretion and low of biliary atresia on abdominal USG, cholangiography
PT as liver insufficiency. The color of stool is also and liver biopsy as shown in Table 2. All infants had
important. About 98% of infants with white stool undergone Kasai procedure.
more than 7 days has been confirmed to have biliary The current management of biliary atresia patients
atresia. On this study, most of cholestasis infants were involves two steps, i.e. Kasai operation (in neonatal
diagnosed at the age of 2.5 months.1 period) which aim to restore bile flow and liver
Anemia can be found in infants with cholestasis transplantation in children for whom the Kasai
due to reduced hepatocytes function or micro- procedure has failed in its primary aim or for whom
hematochezia.5 In this study, most infants were anemic complications of biliary cirrhosis have supervened.
with mean level of hemoglobin was 8.9 (6 to 14.4) g/ Time plays a major role in the treatment of biliary
dL. Therefore, the possibility of hepatocyte damage atresia. The biliary tract between liver and intestines
in those infants should be considered. The laboratory is completely blocked and bile retention then causes
result of ALT serum level can be used as an indicator destruction of the liver itself. Kasai conducted in older
of hepatocyte damage.6 The present study demonstrated infants would reduce the success of the outcome,
increased mean levels of ALT and AST. Some infants because it may have been a process of hepatic cirrhosis.
had ALT and AST levels above 10 times of the normal There were two-year survival rate of 65% and 80%
value, which indicated severe liver damage. of jaundice-free period when Kasai is performed before
Increasing levels of GGT suggests biliary obstruction 60 days of age. If the Kasai is done after the age of 60
since the GGT enzymes are located in the canaliculi. days, the survival rate is 22% and there is 20-35% of
Obstruction may cause further hepatocyte damage. GGT jaundice-free period.13 Of eight infants with biliary
level is more sensitive to detect obstructive jaundice than atresia who had undergone Kasai procedure, two infants
ALP, ALT, and AST.7 The mean serum level of GGT in died after several times of visits; while the outcome of
this study was 326 (16-2,530) u/L, which could a marker the other six infants were unknown due to lost contact
of biliary obstruction in some infants. or could not be traced. Porto-enterostomy performed by
Biliary atresia is characterized by total obstruction an experienced surgeon would give promising results of
of extrahepatic biliary system; however, the cause good bile flow with normal serum bilirubin, which can
is uncertain.8 One of the diagnostic procedures is be achieved in more than 80% of infants with biliary
abdominal ultrasonography (USG).9 The abdominal atresia operated on 60 days of age.13,14

162 The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy

 Biliary Atresia in Infants with Cholestasis

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Correspondence:
Budi Purnomo
Department of Child Health
Harapan Kita Women and Children Hospital
Jl. S. Parman Kav 87 Slipi Jakarta 11420 Indonesia
Phone: +62-21-5668284 Facsimile: +62-21-5601802
E-mail: b_purnomo_56@yahoo.co.id

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