Pediatr Surg Int (1991) 6:309-312
Pediatric
Eur gely
International
© Springer-Vedag 1991
Original article
Fetal bile acids in congenital biliary atresia -
production in the liver and clinical significance
Y. Hata 1 , J. Uchino 1, E Sasaki 1, T. Abe 1, Y. Koike 1, S. Alam 1, K. Kakuya 2, S. Nagano 2, R. Mahara3,
and M. Tohma 3
1First Departmentof Surgery,HokkaidoUniversitySchool of Medicine, 2Departmentof Pediatrics, HokkaidoUniversitySchool of Medicine, and
3 Facultyof PharmaceuticalSciences,Higashi-Nippon-Gakuen University,Sapporo,Japan
Accepted 14 January 1991
Abstract. The l~-hydroxy bile acids have been said to be
fetal bile acids. These bile acids were evaluated in eight
patients with congenital biliary atresia (CBA) using gas
chromatography-mass spectrometry. At the time of opera-
tion 113,3c~,70~,12cz-tetrahydroxy-513-cholan-24-oic acid
(CA-I[3-ol) and 113,3c~,Tc~-trihydroxy-513-cholan-24-oic
acid (CDCA- 113-ol) were 0.46 + 34 gg/ml and
0.72-+0.45 gg/ml, respectively, which was significantly
higher than in the control group. The percentage CA- 1~-ol
of total bile acids showed a tendency to decrease as age
advanced. The grade of hepatic fibrosis ranged from F2 to
F3 and the values and percentages of CA- 1[~-ol and CDCA-
113-ol were relatively higher in F2 than F3 patients. The
percentage of total bile acids gradually increased in
patients without sufficient bile flow but fell sharply after
Kasai's procedure in the patients with sufficient bile flow.
It appears that fetal bile acids are produced in the livers of
CBA patients in the same way as in fetal liver, and that
production continues in patients without good bile secre-
tion even after Kasai's procedure. These results suggest
that these hydroxylases are reactivated in CBA patients.
Key words: Congenital biliary atresia - l[3-hydroxy bile
acids - Fetal bile acids
Introduction
The presence of several unusual bile acids in the serum of
congenital biliary atresia (CBA) patients has been reported,
but their significance has not yet been completely clarified.
Large amounts of 1[~-hydroxy bile acids have recently been
detected in the meconium and bile of neonates, but none
can be found in healthy adults. Therefore, these substances
have been termed fetal bile acids [5].
Offprint requests to: Y. Hata, First Department of Surgery, Hokkaido
University School of Medicine, N-15 W-7, S apporo, Japan
In this study the fetal bile acids were measured in
patients with CBA; the production of these bile acids in the
livers of CBA patients and their clinical significance were
evaluated.
Patients and methods
The experimentalgroup consisted of eight CBA patients (52-143 days
old, mean 98.1+33.7) with porta hepatis obstruction. Five patients
without liver disease, three inguinal hernias, one umbilical hernia, and
one anterioranus 30-78 days old, mean 46.2+-- 19.5) were chosen as the
control group. The serum of these patients was collected and frozen at
-20 °C.
Four l[~-hydroxy bile acids: 1 ~,30~-dihydroxy-513-cholan-24-oic acid
(LCA-I~3-ol); l[3,3c~,12c~-trihydroxy-5~-cholan-24-oic acid (DCA-I~-
ol); l[~,3c~,Tcq12(z-tetrahydroxy-5~-cholan-24-oic acid (CA-I~-ol); and
l~,3cz,7~z-trihydroxy-5~-cholan-24-oic acid (CDCA-I~-ol) were mea-
sured using gas chromatography-massspectrometry [9]. These l~-hy-
droxy serum bile acids were evaluated on the basis of several factors,
e.g., age of the patients at operation, histological grade of hepatic
fibrosis accordingto the classificationof Suruga et al. [8], and status of
bile flow following Kasai's operation. Differences between values
(mean _+ standard deviation) were tested for significance using Stu-
dent's t-test.
Results
Of the four ll~-hydroxy bile acids, DCA-I[3-ol and LCA-
113-ol were not detected in any patient and were accord-
ingly eliminated from our study.
The serum level of CA-I~3-ol was 0.46+0.34 btg/ml,
the percentage being 0.72_+0.45% of total bile acids, in
CBA patients, and was 0.04 _+0.03 gg/ml, 1.60 _+ 1.48% of
total bile acids, in the control group. The serum level of
CDCA- 1~3-ol was 0.72 _+0.45 btg/ml, 1.13 _+0.56% of total
bile acids, in CBA patients and 0.05+0.04gg/ml,
2.06_+ 1.88% of total bile acids, in the control group
(Table 1). The levels of 113-hydroxy bile acids were signif-
icantly elevated in CBA patients compared with the control
group, but there was no significant difference in percentage
of total bile acids between the two groups (Fig. 1).