The role of osteopontin in the development of liver fibrosis in children with chronic viral hepatitis B

  • I.I. Nezgoda
  • L.V. Moroz
  • S. Singh
  • O.O. Singh
Keywords: chronic hepatitis B, children, lymphoblastic leukemia, fibrosis, osteopontin.


The aim of this study was to determine the plasma osteopontin (OPN) level in chronic viral hepatitis B (CHB) children with acute lymphoblastic leukemia (ALL), depending on sex, age, viral load, degree of fibrosis and inflammatory activity in the liver. Were studied 71 children with CHB aged 3 to 17 years, including 41 CHB patients with ALL (main group) and the control group consisted of 20 healthy children. The verification of the CHB diagnosis was performed on the basis of HBV-DNA detection in the blood of patients using PCR technique and ELISA for HBsAg, HBeAg, anti-HBsAg, anti-HBcAg, anti-HBeAg. The degree of fibrosis was determined on the METAVIR scale using Fibrotest. The level of OPN in serum was determined by ELISA. According to results, the level of this glycopeptide in CHB children with ALL is significantly higher than in patients with CHB and healthy individuals (p<0.05). Irrespective of gender, age, and viral load, significantly higher values of OPN were detected in CHB children with ALL than in the rest of the individuals. Many children of the main group have been diagnosed with fibrosis (F1-F3) with different inflammatory activity process in the liver (A0-A3). In CHB patients with ALL, the level of plasma OPN positively correlates with the degree of fibrosis and inflammatory activity in the liver (p<0.05). Osteopontin claims to be a new non-invasive biomarker of liver fibrosis.


1. Anastasij, I. A. (2009). Neinvazivnye metody ocenki fibroza pecheni. Novosti mediciny i farmacii: Infekcionnye bolezni, gepatologiya, 281. Vzyato z [in Russian].

2. Berezenko, V. S. (2007). Kliniko-patohenetychni osoblyvosti fibrohenezu pechinky pry khronichnykh hepatytakh u ditei ta shliakhy yoho medykamentoznoi korektsii (Dys. d. med. nauk). DU «Instytut pediatrii, akusherstva i hinekolohii Akademii medychnykh nauk Ukrainy», Kyiv. [in Ukrainian].

3. Berezenko, V. S., & Tsarova, O. V. (2016). Kharakterystyka fibrozu pechinky u ditei z khronichnym virusnym hepatytom S za okremymy priamymy ta nepriamymy markeramy. Visnyk morfolohii, 22 (1), 113-117. [in Ukrainian].

4. Pavlov, Ch. S., & Ivashkin, V. T. (2007). Kak ocenit i snizit risk vozniknoveniya fibroza, cirroza i gepatocellyulyarnoj karcinomy u pacientov s hronicheskoj infekciej virusami gepatita B i C. Rossijskij zhurnal gastroenterologii, gepatologii, koloproktologii, 17 (5), 16-24. [in Russian].

5. Pirogova, I. Yu. (2012). Diagnostika fibroza pecheni u pacientov s hronicheskim gepatitom V i S i ego klinicheskoe znachenie. (Dis. d. med. nauk) dissertacionnyj sovet pri FGBU «Uchebno-nauchnyj medicinskij centr» Upravleniya delami Prezidenta Rossijskoj Federacii, Moskva. [in Russian].

6. Tsarova, O. V. (2017). Kliniko-diahnostychni kryterii prohresuvannia khronichnykh virusnykh hepatytiv V ta S u ditei (Dys. kand. med. nauk). DU «Instytut pediatrii, akusherstva i hinekolohii NAMN Ukrainy», Kyiv. [in Ukrainian].

7. Shadrin, O. H., Cherneha, N. F., Diukareva, S. V., & Mohylnyi, A. I. (2014). Kliniko-paraklinichni osoblyvosti perebihu hepatytiv V i S u ditei rannoho viku z perynatalnym infikuvanniam. Neonatolohiia, khirurhiia ta perynatalna medytsyna, 4 (2) 12, 96-100. [in Ukrainian].

8. Abeer, M. N., Hala, I. M. Hussien, Heba, F.P., & Naglaa, A. M. (2011). Clinical Utility of Plasma Osteopontin in HCV-Related Chronic Liver Disease Patients. Medical Journal of Cairo University, 79(1), 233-236.

9. Global Hepatitis Report, World Health Organization, Geneva, 2017. Retrieved from

10. Golubovska, O. (2017). Local situation in Ukraine. 3rd Central and Eastern European Meeting on Viral Hepatitis and Co-infection with HIV, 27-28 September 2017, Ljubljana, Slovenia / Reviews in Anviral therapy & Infectious Diseases 2017.

11. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection World Health Organization, Geneva, 2015.

12. Honsawek, S., Vejchapipat, P., Chongsrisawat, V., Thawornsuk, N., & Poovorawan Y. (2011). Association of circulating osteopontin levels with clinical outcomes in postoperative biliary atresia. Pediatric Surgery International, 27(3): 283–288. doi: 10.1007/s00383-010-2799-7.

13. Huang, W., Zhu, G., Huang, M., Lou, G., Liu, Y., & Wang, S. (2010). Plasma osteopontin concentration correlates with the severity of hepatic fibrosis and inflammation in HCV-infected subjects. International J. of clinical chemistry, 411, 675-8.

14. Iida, T., Wagatsuma, K., Hirayama, D., & Nakase, H. (2017). Is Osteopontin a Friend or Foe of Cell Apoptosis in Inflammatory Gastrointestinal and Liver Diseases? International Journal of Molecular Sciences, 19(1) 7, 1-15.

15. Karpinsky, G., Fatyga, A., Krawczyk, M.A., Chamera, M., Sande, N., Szmyd, D. … Bien, E. (2017). Osteopontin: its potential role in cancer of children and young adults. Biomark Med., 11(4), 389-402.

16. Kim, J., Ki, S.S., Lee, S.D., Han, C.J., Kim, Y.C., Park, S.H. … Jeong, S.H. (2006). Elevated plasma osteopontin levels in patients with hepatocellular carcinoma. American Journal of Gastroenterology, 101, 2051-2059. DOI: 10.1111/j.1572-0241.2006.00679.x.

17. Lee, H.J., Yeon, J.E., Suh, S.J., Lee, S.J., Yoon, E.L., Kang, K. … Byun K.S. (2014). Clinical Utility of Plasma Glypican-3 and Osteopontin as Biomarkers of Hepatocellular Carcinoma. Gut and Liver, 8, 177-185.

18. Lee S.H., Seo G.S., Park Y.N., Yoo T.M., & Sohn D.H. (2004). Effects and regulation of osteopontin in rat hepatic stellate cells. Biochem. Pharmacol., 68(12): 2367-2378.

19. Libra, M., Indelicato, M., De Re, V. Zignego, A.L., Chiocchetti, A., Malaponte, G. ... Mazzarino, M.C. (2005). Elevated Serum Levels of Osteopontin in HCV-Associated Lymphoproliferative Disorders. Cancer Biol Ther., 4(11), 1192-4.

20. Nogueira da Costa, A., Plymoth, A., Santos-Silva, D., Ortiz-Cuaran, S., Camey, S., Guilloreau, P. … Hainaut, P. (2015). Osteopontin and Latent-TGF β Binding-Protein 2 as potential diagnostic markers for HBV-related Hepatocellular Carcinoma. International Journal of Cancer, 136(1): 172-181.

21. Patouraux, S., Bonnafous, S., Voican, C.S. Anty, R., Saint-Paul, M.-Ch., Rosenthal-Allieri, M.-A. … Gual, Ph. (2012). The Osteopontin Level in Liver, Adipose Tissue and Serum Is Correlated with Fibrosis in Patients with Alcoholic Liver Disease. PLoS ONE., 7(4): e35612.

22. Acton, Q.A. (2012). Liver Fibrosis: New Insights for the Healthcare Professional. Atlanta, Georgia: Scholarly Editions.Ramaiah, S.K., & Rittling, S. (2008) Pathophysiological Role of Osteopontin in Hepatic Inflammation, Toxicity, and Cancer. Toxicological Sciences, 103(1): 4-13.

23. Samy, A.H., Saleh, S.A., & Abdella, H.M. (2015). Plasma osteopontin as a biomarker test in predicting liver fibrosis in Genotype 4 Chronic Hepatitis C infected patients. International J. of Microbiology and Immunology Research, 3(3): 036-044.

24. Sase, S.P., Ganu, J.V., & Nagane, N. (2012). Osteopontin: a novel protein molecule, Indian Medical Gazette, 62-66.

25. Shang, S., Plymoth, FA., Shaokui, Ge., Feng, Z., Rosen, H.R., Sangrajrang, S., … Beretta, L. (2012). Identification of Osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology, 55(2): 483-490. doi:10.1002/hep.24703.

26. Shimakawa, Y., Lemoine, M., Bottomley, C., Njai, H.F., Ndow, G., Jatta, A., … Hall, A.J. (2015). Birth order and risk of hepatocellular carcinoma in chronic carriers of hepatitis B virus: a case-control study in The Gambia. Liver Int. 35(10): 2318–2326.

27. Suzuki, H., Amizuka, N., Oda, K., Li, M., Yoshie, H., Ohshima, H., … Maeda, T. (2005). Histological evidence of altered distribution of osteocytes and bone matrix synthesis in klotho-deficient mice. Arch Histol Cytol; 68(5): 371-381.

28. Syn, W.K., Choi, S.S., Liaskou, E., Karaca, G.F., Agboola, K.M., Oo, Y.H., … Diehl, A.M. (2011). Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis. Hepatology, 53:106-115. doi: 10.1002/hep.23998.

29. Trépo, C., Chan, H.L., & Lok, A. (2014). Hepatitis B virus infection. Lancet, 384(9959): 2053-2063.

30. Van Damme P. (2017) Hepatitis B Vaccines, In Vaccines 6th Edition. Plotkin SA, Orenstein WA, Offit PA editors, Elsevier Sanders, 2017.

31. Weber GF. (2011). The cancer biomarker osteopontin: combination with other markers. Cancer Genomics Proteomics, 8(6): 263-288.

32. Wen Y., Jeong S., Xia Q., & Kong X. (2016). Role of Osteopontin in Liver Diseases. Int. J. Biol. Sci, 12(9): 1121-8.
How to Cite
Nezgoda, I., Moroz, L., Singh, S., & Singh, O. (2017). The role of osteopontin in the development of liver fibrosis in children with chronic viral hepatitis B. Biomedical and Biosocial Anthropology, (29), 154-160. Retrieved from