The purpose of this study was to determine the possible
role of
serum levels of
tissue inhibitors of
metalloproteinase-1 (
TIMP-1) in the pathogenesis of the progressive
inflammation and
fibrosis in
biliary atresia (BA).
Serum concentrations of
TIMP-1 were measured in 57 BA
patients and 15 healthy controls using commercially available
enzyme-linked immunosorbent assays. The mean ages of the BA
patients and the controls were 6.1 +/- 0.6 and 6.7 +/- 1.1 years, respectively. The
patients were categorized into two groups according to their clinical
outcomes:
patients with
jaundice (total
bilirubin > or = 2 mg/dl) and
patients without
jaundice (total
bilirubin < 2 mg/dl). In our study,
serum levels of
TIMP-1 were significantly higher in the BA
patients than in
healthy subjects (4.8 +/- 0.4 vs. 3.5 +/- 0.3 ng/ml, respectively; p < 0.05). Additionally,
serum levels of
TIMP-1 significantly increased in the BA
patients with
jaundice in comparison to those without
jaundice (6.3 +/- 0.7 vs. 3.1 +/- 0.3 ng/ml, respectively; p = 0.001).
Patients with persistent
jaundice had lower levels of
albumin but had greater levels of
aspartate aminotransferase,
alanine aminotransferase,
alkaline phosphatase, and
gamma glutamyl transpeptidase compared with
patients without
jaundice. Furthermore,
patients with
portal hypertension (
PH) had higher
TIMP-1 levels than those without
PH (5.3 +/- 0.4 vs. 1.9 +/- 0.3 ng/ml, respectively; p < 0.001). It is concluded that
serum levels of
TIMP-1 increased in
patients with BA. The significant increase in
TIMP-1 levels is related to the presence of
PH and the severity of
jaundice. The elevated
TIMP-1 levels may reflect the degree of hepatic
fibrosis and development of
PH. The data suggest that
TIMP-1 may
play a
role in the pathophysiology of post-Kasai BA.