Abstract
Background and aim: Biliary atresia (BA) is an intractable neonatal liver disease characterized by progressive fibrosclerotic obliteration of the extrahepatic biliary tree. The aim of this study was to evaluate serum galectin-3 in postoperative BA patients and the association between galectin-3, clinical outcome and liver stiffness score.
Methods: 58 BA patients post Kasai operation and 20 controls were enrolled. None of the patients had undergone liver transplantation. BA patients were classified into 2 groups according to their serum total bilirubin (TB) levels (TB<2 mg/dL, no jaundice vs. TB≥2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT) levels (ALT<45 IU/L, normal ALT vs. ALT≥45 IU/L, elevated ALT). Serum galectin-3 levels were determined by enzyme-linked immunosorbent assay. Liver stiffness scores were measured by transient elastography (FibroScan).
Results: BA patients had higher serum galectin-3 levels (5.1±0.3 vs. 3.8±0.4 ng/mL, p=0.01) and greater liver stiffness values than healthy controls (29.7±3.0 vs. 5.1±0.5 kPa, p<0.001). Serum galectin-3 levels were markedly elevated in BA patients with jaundice compared to those without jaundice (6.4±0.5 vs. 4.4±0.3 ng/mL, p=0.001). Furthermore, BA patients with elevated ALT displayed significantly higher levels of serum galectin-3 than those with normal ALT (5.9±0.4 vs. 3.8±0.3 ng/mL, p=0.001). Additionally, BA patients with portal hypertension had considerably higher serum galectin-3 levels than those without portal hypertension (6.1±0.4 vs. 3.7±0.3 ng/mL, p<0.001).
Conclusions: Increased serum galectin-3 is associated with a poor outcome in postoperative BA patients. Serum galectin-3 could be used as a biochemical parameter reflecting the deterioration of liver function and the severity of liver fibrosis in postoperative BA.
Key words
biliary atresia - galectin-3 - jaundice - liver stiffness - portal hypertension
References
-
1
Hartley JL, Davenport M, Kelly DA.
Biliary atresia.
Lancet.
2009;
374
1704-1713
-
2
Bassett MD, Murray KF.
Biliary atresia: recent progress.
J Clin Gastroenterol.
2008;
42
720-729
-
3
Erlichman J, Hohlweg K, Haber BA.
Biliary atresia: how medical complications and therapies impact outcome.
Expert Rev Gastroenterol Hepatol.
2009;
3
425-434
-
4
A-Kader HH, Abdel-Hameed A, Al-Shabrawi M. et al .
Is biliary atresia an autoimmune disease?.
Eur J Gastroenterol Hepatol.
2003;
15
447
-
5
Barondes SH, Castronovo V, Cooper DN. et al .
Galectins: a family of animal beta-galactoside-binding lectins.
Cell.
1994;
76
597-598
-
6
Kasai K, Hirabayashi J.
Galectins: a family of animal lectins that decipher glycocodes.
J Biochem.
1996;
119
1-8
-
7
Liu FT.
Molecular biology of IgE-binding protein, IgE-binding factors, and IgE receptors.
Crit Rev Immunol.
1990;
10
289-306
-
8
Inohara H, Akahani S, Raz A.
Galectin-3 stimulates cell proliferation.
Exp Cell Res.
1998;
245
294-302
-
9
Inohara H, Raz A.
Functional evidence that cell surface galectin-3 mediates homotypic cell adhesion.
Cancer Res.
1995;
55
3267-3271
-
10
Yang RY, Hsu DK, Liu FT.
Expression of galectin-3 modulates T-cell growth and apoptosis.
Proc Natl Acad Sci USA.
1996;
93
6737-6742
-
11
Henderson NC, Sethi T.
The regulation of inflammation by galectin-3.
Immunol Rev.
2009;
230
160-171
-
12
Maeda N, Kawada N, Seki S. et al .
Stimulation of proliferation of rat hepatic stellate cells by galectin-1 and galectin-3 through different intracellular signaling pathways.
J Biol Chem.
2003;
278
18938-18944
-
13
Lok DJ, Van Der Meer P, de la Porte PW. et al .
Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study.
Clin Res Cardiol.
2010;
99
323-328
-
14
Wang L, Friess H, Zhu Z. et al .
Galectin-1 and galectin-3 in chronic pancreatitis.
Lab Invest.
2000;
80
1233-1241
-
15
Nishi Y, Sano H, Kawashima T. et al .
Role of galectin-3 in human pulmonary fibrosis.
Allergol Int.
2007;
56
57-65
-
16
Henderson NC, Mackinnon AC, Farnworth SL. et al .
Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis.
Am J Pathol.
2008;
172
288-298
-
17
Kongtawelert P, Ghosh P.
A method for the quantitation of hyaluronan (hyaluronic acid) in biological fluids using a labeled avidin-biotin technique.
Anal Biochem.
1990;
185
313e8
-
18
Wai CT, Greenson JK, Fontana RJ. et al .
A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C.
Hepatology.
2003;
38
518-526
-
19
Chongsrisawat V, Vejchapipat P, Poovorawan Y.
Serum vascular endothelial growth factor per platelet count in patients with biliary atresia.
Asian Biomed.
2010;
4
223-229
-
20
Chayanupatkul M, Honsawek S, Vejchapipat P. et al .
Elevated serum bone morphogenetic protein 7 levels and clinical outcome in children with biliary atresia.
Eur J Pediatr Surg.
2009;
19
246-250
-
21
Honsawek S, Chongsrisawat V, Vejchapipat P. et al .
Association of serum levels of tissue inhibitors of metalloproteinase-1 with clinical outcome in children with biliary atresia.
Asian Pac J Allergy Immunol.
2006;
24
161-166
-
22
Honsawek S, Chongsrisawat V, Vejchapipat P. et al .
Serum interleukin-8 in children with biliary atresia: relationship with disease stage and biochemical parameters.
Pediatr Surg Int.
2005;
21
73-77
-
23
Matsuda Y, Yamagiwa Y, Fukushima K. et al .
Expression of galectin-3 involved in prognosis of patients with hepatocellular carcinoma.
Hepatol Res.
2008;
38
1098-1111
-
24
Hsu DK, Dowling CA, Jeng KC. et al .
Galectin-3 expression is induced in cirrhotic liver and hepatocellular carcinoma.
Int J Cancer.
1999;
81
519-526
-
25
Henderson NC, Mackinnon AC, Farnworth SL. et al .
Galectin-3 regulates myofibroblast activation and hepatic fibrosis.
Proc Natl Acad Sci USA.
2006;
103
5060-5065
-
26
Butscheid M, Hauptvogel P, Fritz P. et al .
Hepatic expression of galectin-3 and receptor for advanced glycation end products in patients with liver disease.
J Clin Pathol.
2007;
60
415-418
-
27
Inufusa H, Nakamura M, Adachi T. et al .
Role of galectin-3 in adenocarcinoma liver metastasis.
Int J Oncol.
2001;
19
913-919
-
28
Shimonishi T, Miyazaki K, Kono N. et al .
Expression of endogenous galectin-1 and galectin-3 in intrahepatic cholangiocarcinoma.
Hum Pathol.
2001;
32
302-310
Correspondence
Dr. Sittisak Honsawek
Faculty of Medicine
Chulalongkorn University
Biochemistry
Department of Biochemistry
Faculty of Medicine
Bangkok 10330
Thailand
Phone: + 66 2 256 4482
Fax: + 66 2 256 4482
Email: Sittisak.H@chula.ac.th