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Association of circulating osteopontin levels with clinical outcomes in postoperative biliary atresia

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Abstract

Purpose

Biliary atresia (BA) is one of the most serious liver disorders in children. The aims of the present study were to investigate circulating levels of osteopontin in BA children compared with healthy controls and to evaluate the relationship between circulating osteopontin and therapeutic outcome of BA patients.

Methods

Fifty-nine BA patients post-Kasai operation and 13 healthy children were recruited. The patients were divided into two groups according to their serum total bilirubin levels (TB < 2, jaundice-free vs. TB ≥ 2 mg/dL, persistent jaundice) and alanine aminotransferase (ALT < 45, normal ALT vs. ALT ≥ 45 IU/L, elevated ALT). Plasma osteopontin levels were analyzed using commercial enzyme-linked immunosorbent assay.

Results

The circulating osteopontin was higher in BA children compared with that of healthy controls (146.9 ± 19.1 vs. 28.0 ± 8.4 ng/mL, P = 0.001). The BA patients with persistent jaundice had more increased plasma osteopontin levels than those without jaundice (157.8 ± 47.9 vs. 27.5 ± 6.4 ng/mL, P = 0.001). Furthermore, plasma osteopontin levels in BA patients with elevated ALT were significantly higher than those with normal ALT (103.2 ± 29.2 vs. 24.5 ± 7.9 ng/mL, P = 0.01). In addition, circulating osteopontin was positively correlated with serum total bilirubin (r = 0.526, P < 0.001) and with serum ALT (r = 0.575, P < 0.001). Subsequent analysis showed that the BA patients with portal hypertension had more elevated plasma osteopontin compared to those without portal hypertension (116.7 ± 31.1 vs. 19.5 ± 9.3 ng/mL, P = 0.01).

Conclusion

Increased circulating osteopontin was associated with the development of hepatic dysfunction and portal hypertension in BA patients. Circulating osteopontin may serve as a possible marker reflecting disease severity and monitoring the disease progression in postoperative BA patients.

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References

  1. Davenport M (2005) Biliary atresia. Semin Pediatr Surg 14:42–48

    Article  PubMed  Google Scholar 

  2. Kobayashi H, Stringer MD (2003) Biliary atresia. Semin Neonatol 8:383–391

    Article  PubMed  Google Scholar 

  3. Davenport M, Gonde C, Redkar R, Koukoulis G, Tredger M, Mieli-Vergani G, Portmann B, Howard ER (2001) Immunohistochemistry of the liver and biliary tree in extrahepatic biliary atresia. J Pediatr Surg 36:1017–1025

    Article  CAS  PubMed  Google Scholar 

  4. A-Kader HH, Abdel-Hameed A, Al-Shabrawi M, Mohsen N, El-Karaksy H, Hassanein B, Elsayed B, Abdel-Khalik MK, Karjoo M (2003) Is biliary atresia an autoimmune disease? Eur J Gastroenterol Hepatol 15:447

    Article  PubMed  Google Scholar 

  5. Kobayashi H, Horikoshi K, Yamataka A, Lane GJ, Furuhata A, Sueyoshi N, Miyano T (2001) Are stable postoperative biliary atresia patients really stable? Pediatr Surg Int 17:104–107

    Article  CAS  PubMed  Google Scholar 

  6. Vejchapipat P, Theamboonlers A, Chaokhonchai R, Chongsrisawat V, Chittmittrapap S, Poovorawan Y (2004) Serum hepatocyte growth factor and clinical outcome in biliary atresia. J Pediatr Surg 39:1045–1049

    Article  PubMed  Google Scholar 

  7. Honsawek S, Chongsrisawat V, Vejchapipat P, Thawornsuk N, Poovorawan Y (2008) High levels of serum basic fibroblast growth factor in children with biliary atresia. Hepatogastroenterology 55:1184–1188

    CAS  PubMed  Google Scholar 

  8. Bautista DS, Saad Z, Chambers AF, Tonkin KS, O’Malley FP, Singhal H, Tokmakejian S, Bramwell V, Harris JF (1996) Quantification of osteopontin in human plasma with an ELISA: basal levels in pre- and postmenopausal women. Clin Biochem 29:231–239

    Article  CAS  PubMed  Google Scholar 

  9. Denhardt DT, Giachelli CM, Rittling SR (2001) Role of osteopontin in cellular signaling and toxicant injury. Annu Rev Pharmacol Toxicol 41:723–749

    Article  CAS  PubMed  Google Scholar 

  10. Uede T, Katagiri Y, Iizuka J, Murakami M (1997) Osteopontin, a coordinator of host defense system: a cytokine or an extracellular adhesive protein? Microbiol Immunol 41:641–648

    CAS  PubMed  Google Scholar 

  11. Denhardt DT, Guo X (1993) Osteopontin: a protein with diverse functions. FASEB J 7:1475–1482

    CAS  PubMed  Google Scholar 

  12. Kawashima R, Mochida S, Matsui A, YouLuTuZ Y, Ishikawa K, Toshima K, Yamanobe F, Inao M, Ikeda H, Ohno A, Nagoshi S, Uede T, Fujiwara K (1999) Expression of osteopontin in Kupffer cells and hepatic macrophages and stellate cells in rat liver after carbon tetrachloride intoxication: a possible factor for macrophage migration into hepatic necrotic areas. Biochem Biophys Res Commun 256:527–531

    Article  CAS  PubMed  Google Scholar 

  13. Bezerra JA, Tiao G, Ryckman FC, Alonso M, Sabla GE, Shneider B, Sokol RJ, Aronow BJ (2002) Genetic induction of proinflammatory immunity in children with biliary atresia. Lancet 360:1653–1659

    Article  PubMed  Google Scholar 

  14. Whitington PF, Malladi P, Melin-Aldana H, Azzam R, Mack CL, Sahai A (2005) Expression of osteopontin correlates with portal biliary proliferation and fibrosis in biliary atresia. Pediatr Res 57:837–844

    Article  CAS  PubMed  Google Scholar 

  15. Huang L, Wei MF, Feng JX (2008) Abnormal activation of OPN inflammation pathway in livers of children with biliary atresia and relationship to hepatic fibrosis. Eur J Pediatr Surg 18:224–229

    Article  CAS  PubMed  Google Scholar 

  16. Ashkar S, Weber GF, Panoutsakopoulou V, Sanchirico ME, Jansson M, Zawaideh S, Rittling SR, Denhardt DT, Glimcher MJ, Cantor H (2000) Eta-1 (osteopontin): an early component of type-1 (cell-mediated) immunity. Science 287:860–864

    Article  CAS  PubMed  Google Scholar 

  17. Atalar E, Ozturk E, Ozer N, Haznedaroglu IC, Kepez A, Coskun S, Aksoyek S, Ovunc K, Kes S, Kirazli S, Ozmen F (2006) Plasma soluble osteopontin concentrations are increased in patients with rheumatic mitral stenosis and associated with the severity of mitral valve calcium. Am J Cardiol 98:817–820

    Article  CAS  PubMed  Google Scholar 

  18. Comabella M, Pericot I, Goertsches R, Nos C, Castillo M, Blas Navarro J, Río J, Montalban X (2005) Plasma osteopontin levels in multiple sclerosis. J Neuroimmunol 158:231–239

    Article  CAS  PubMed  Google Scholar 

  19. Honsawek S, Tanavalee A, Sakdinakiattikoon M, Chayanupatkul M, Yuktanandana P (2009) Correlation of plasma and synovial fluid osteopontin with disease severity in knee osteoarthritis. Clin Biochem 42:808–812

    Article  CAS  PubMed  Google Scholar 

  20. Wu CY, Wu MS, Chiang EP, Wu CC, Chen YJ, Chen CJ, Chi NH, Chen GH, Lin JT (2007) Elevated plasma osteopontin associated with gastric cancer development, invasion and survival. Gut 56:782–789

    Article  CAS  PubMed  Google Scholar 

  21. Arai M, Yokosuka O, Kanda T, Fukai K, Imazeki F, Muramatsu M, Seki N, Miyazaki M, Ochiai T, Hirasawa H, Saisho H (2006) Serum osteopontin levels in patients with acute liver dysfunction. Scand J Gastroenterol 41:102–110

    Article  CAS  PubMed  Google Scholar 

  22. Zhao L, Li T, Wang Y, Pan Y, Ning H, Hui X, Xie H, Wang J, Han Y, Liu Z, Fan D (2008) Elevated plasma osteopontin level is predictive of cirrhosis in patients with hepatitis B infection. Int J Clin Pract 62:1056–1062

    Article  CAS  PubMed  Google Scholar 

  23. Matsui A, Mochida S, Ohno A, Nagoshi S, Hirose T, Fujiwara K (2004) Plasma osteopontin levels in patients with fulminant hepatitis. Hepatol Res 29:202–206

    Article  CAS  PubMed  Google Scholar 

  24. Kim J, Ki SS, Lee SD, Han CJ, Kim YC, Park SH, Cho SY, Hong YJ, Park HY, Lee M, Jung HH, Lee KH, Jeong SH (2006) Elevated plasma osteopontin levels in patients with hepatocellular carcinoma. Am J Gastroenterol 101:2051–2059

    Article  CAS  PubMed  Google Scholar 

  25. Zhang H, Ye QH, Ren N, Zhao L, Wang YF, Wu X, Sun HC, Wang L, Zhang BH, Liu YK, Tang ZY, Qin LX (2006) The prognostic significance of preoperative plasma levels of osteopontin in patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 132:709–717

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The present study has been supported by grants from Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University, Thailand Research Fund, and the Commission on Higher Education. The authors are profoundly grateful to the entire staff of the Center of Excellence in Clinical Virology, Chulalongkorn University and King Chulalongkorn Memorial Hospital for their combined effort in this study.

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Correspondence to Sittisak Honsawek.

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Honsawek, S., Vejchapipat, P., Chongsrisawat, V. et al. Association of circulating osteopontin levels with clinical outcomes in postoperative biliary atresia. Pediatr Surg Int 27, 283–288 (2011). https://doi.org/10.1007/s00383-010-2799-7

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  • DOI: https://doi.org/10.1007/s00383-010-2799-7

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