Elevation of Serum Galectin-3 and Liver Stiffness Measured by Transient Elastography in Biliary Atresia

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