早產兒肝內 膽汁滯留之藥物治療及分子機轉
Date Issued
2002
Date
2002
Author(s)
陳慧玲
DOI
902314B002157
Abstract
Total parenteral nutrition associated liver
disease (PNALD) is a major and potentially
lethal complication in patients receiving
long-term parenteral nutrition therapy. The
key predisposing factors for the development
of PNALD are prematurity and low birth
weight. Immaturity of hepatic function
appears to be important in the pathogenesis of
PNALD in premature infants.
A number of pharmacologic agents have
been proposed for the prevention and
treatment of PNALD but no conclusive
results have been documented for their
beneficial effects. Ursodeoxycholic acid
(UDCA) is a hydrophilic bile acid and has
been widely used in various cholestatic liver
diseases in adult and in children. UDCA
improves bile flow and reduces serum and
liver bilirubin concentrations in piglets with
PNALD. Bile salt export pump (BSEP), an
ATP-dependent bile acid exporter has
recently been cloned and proved to be the
major canalicular bile salt transporter. The
role of BSEP in PNALD has not been
reported. In this report we investigate the
effect of UDCA treatment in premature
patients with PNALD and test the expression
of BSEP in their liver samples.
Results: A total of 35 premature patients with
TPN related cholestasis were recruited.Twenty-two of them were treated with UDCA
30 mg/kg/d and 13 patients in the control
group were not treated. The total bilirubin
levels decreased in 95% (21/22) treated 46%
(6/13) control patients. The mean change of
bilirubin was -5.4 + 5.6 mg/dl in the treatment
group and 1.7+ 6.5 mg/dl in the control group.
The mean changes of alanine
aminotransferase (ALT) levels were -25 + 58
U/L in the treatment group and 34 + 17 U/L
in the control group. Expression of Bile salt
export pump (BSEP) was tested by using
RT-PCR. Two of the five premature patients
of TPN liver disease and 6/7 patients of
biliary atresia were tested positive for BSEP.
Immunofluorescent staining showed weak
canalicular staining and some cytoplasmic
staining.
The results showed that UDCA treatment
was effective in decreasing the bilirubin
levels and ALT levels in premature patients
with PNALD. Liver from patients with
PNALD liver disease had lower expression
levels of BSEP than biliary atresia. The
mechanism of TPN cholestasis may be
related to abnormal BSEP expression and
bile salt excretion function.
Subjects
Cholestasis
prematurity
infants
total parenteral nutrition
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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