Serum osteopontin is a predictor of prognosis for HBV‑associated acute‑on‑chronic liver failure

Liu,Longgen; Lu,Jianchun; Ye,Chunyan; Lin,Lin; Zheng,Shuqin; Zhang,Hongyu; Lan,Qing; Xue,Yuan

doi:10.3892/br.2017.1027

Serum osteopontin is a predictor of prognosis for HBV‑associated acute‑on‑chronic liver failure

Authors:
- Longgen Liu
- Jianchun Lu
- Chunyan Ye
- Lin Lin
- Shuqin Zheng
- Hongyu Zhang
- Qing Lan
- Yuan Xue
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Affiliations: Institute for the Study of Liver Diseases, The Third People's Hospital of Changzhou, Changzhou, Jiangsu 213000, P.R. China, Department of Infectious Diseases, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650051, P.R. China
Published online on: December 13, 2017 https://doi.org/10.3892/br.2017.1027
Pages: 166-171

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Abstract

Acute‑on‑chronic liver failure (ACLF) is a syndrome with a high rate of short‑term mortality, and clinically it is important to identify patients at high risk of mortality. The present study evaluated the value of osteopontin (OPN) in the prediction of 90‑day mortality in patients with ACLF. A total of 54 patients with HBV‑associated ACLF were enrolled, and serum OPN levels were determined in a prospective, observational study design. Survival analysis was performed using Kaplan‑Meier curves, and multivariate Cox proportional hazards regression was used to analyze independent risk factors of mortality. Serum OPN was significantly higher in HBV‑ACLF patients compared with patients with chronic hepatitis B and healthy controls (both P<0.01), and furthermore, was higher in those patients who succumbed to HBV‑ACLF compared with surviving patients (P<0.05). OPN level positively correlated with total bilirubin (r=0.554, P<0.001), Model for End‑Stage Liver Disease (MELD) score (r=0.234, P=0.038), MELD‑Na score (r=0.379, P=0.005) and monocyte count (r=0.282, P=0.039), and OPN was an independent risk factor for 90‑day mortality in ACLF (P=0.021, odds ratio=1.104, 95% confidence interval: 1.003‑1.116). Furthermore, ACLF patients were stratified into three groups according to serum OPN levels (low mortality risk: <6,135 ng/ml; intermediate risk: 6,135‑9,043 ng/ml; and high risk: >9,043 ng/ml), for which the 90‑day mortality rates were 27.78 (5/18), 52.94 (9/17) and 73.68% (14/19), respectively, and those in the high risk had a poorer prognosis compared with the low risk group (P=0.009). In conclusion, serum OPN may be an independent risk factor associated with HBV‑ACLF prognosis.

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1	Hernaez R, Solà E, Moreau R and Ginès P: Acute-on-chronic liver failure: An update. Gut. 66:541–553. 2017. View Article : Google Scholar : PubMed/NCBI
2	Arroyo V and Jalan R: Acute-on-chronic liver failure: Definition, diagnosis, and clinical characteristics. Semin Liver Dis. 36:109–116. 2016. View Article : Google Scholar : PubMed/NCBI
3	Arroyo V and Moreau R: Diagnosis and prognosis of acute on chronic liver failure (ACLF) in cirrhosis. J Hepatol. 66:451–453. 2017. View Article : Google Scholar : PubMed/NCBI
4	Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL, D'Amico G, Dickson ER and Kim WR: A model to predict survival in patients with end-stage liver disease. Hepatology. 33:464–470. 2001. View Article : Google Scholar : PubMed/NCBI
5	Biggins SW, Kim WR, Terrault NA, Saab S, Balan V, Schiano T, Benson J, Therneau T, Kremers W, Wiesner R, et al: Evidence-based incorporation of serum sodium concentration into MELD. Gastroenterology. 130:1652–1660. 2006. View Article : Google Scholar : PubMed/NCBI
6	Diao H, Iwabuchi K, Li L, Onoe K, Van Kaer L, Kon S, Saito Y, Morimoto J, Denhardt DT, Rittling S, et al: Osteopontin regulates development and function of invariant natural killer T cells. Proc Natl Acad Sci USA. 105:pp. 15884–15889. 2008; View Article : Google Scholar : PubMed/NCBI
7	Diao H, Kon S, Iwabuchi K, Kimura C, Morimoto J, Ito D, Segawa T, Maeda M, Hamuro J, Nakayama T, et al: Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases. Immunity. 21:539–550. 2004. View Article : Google Scholar : PubMed/NCBI
8	Pereira TA, Syn WK, Pereira FE, Lambertucci JR, Secor WE and Diehl AM: Serum osteopontin is a biomarker of severe fibrosis and portal hypertension in human and murine schistosomiasis mansoni. Int J Parasitol. 46:829–832. 2016. View Article : Google Scholar : PubMed/NCBI
9	Matsue Y, Tsutsumi M, Hayashi N, Saito T, Tsuchishima M, Toshikuni N, Arisawa T and George J: Serum osteopontin predicts degree of hepatic fibrosis and serves as a biomarker in patients with hepatitis C virus infection. PLoS One. 10:e01187442015. View Article : Google Scholar : PubMed/NCBI
10	Zhao L, Li T, Wang Y, Pan Y, Ning H, Hui X, Xie H, Wang J, Han Y, Liu Z, et al: Elevated plasma osteopontin level is predictive of cirrhosis in patients with hepatitis B infection. Int J Clin Pract. 62:1056–1062. 2008. View Article : Google Scholar : PubMed/NCBI
11	Fan X, He C, Jing W, Zhou X, Chen R, Cao L, Zhu M, Jia R, Wang H, Guo Y, et al: Intracellular Osteopontin inhibits toll-like receptor signaling and impedes liver carcinogenesis. Cancer Res. 75:86–97. 2015. View Article : Google Scholar : PubMed/NCBI
12	Patouraux S, Rousseau D, Rubio A, Bonnafous S, Lavallard VJ, Lauron J, Saint-Paul MC, Bailly-Maitre B, Tran A, Crenesse D, et al: Osteopontin deficiency aggravates hepatic injury induced by ischemia-reperfusion in mice. Cell Death Dis. 5:e12082014. View Article : Google Scholar : PubMed/NCBI
13	Liu Y, Cao L, Chen R, Zhou X, Fan X, Liang Y, Jia R, Wang H, Liu G, Guo Y, et al: Osteopontin Promotes Hepatic Progenitor Cell Expansion and Tumorigenicity via Activation of β-Catenin in Mice. Stem Cells. 33:3569–3580. 2015. View Article : Google Scholar : PubMed/NCBI
14	Lee SH, Park JW, Woo SH, Go DM, Kwon HJ, Jang JJ and Kim DY: Suppression of osteopontin inhibits chemically induced hepatic carcinogenesis by induction of apoptosis in mice. Oncotarget. 7:87219–87231. 2016.PubMed/NCBI
15	Srungaram P, Rule JA, Yuan HJ, Reimold A, Dahl B, Sanders C and Lee WM: Acute Liver Failure Study Group: Plasma osteopontin in acute liver failure. Cytokine. 73:270–276. 2015. View Article : Google Scholar : PubMed/NCBI
16	Tajiri T, Tate G, Kunimura T, Endo Y, Inoue K, Mitsuya T, Morohoshi T and Yoshiba M: Osteopontin expression in proliferated bile ductules: The correlation with liver damage in fulminant hepatitis. Dig Dis Sci. 50:188–195. 2005. View Article : Google Scholar : PubMed/NCBI
17	Arai M, Yokosuka O, Kanda T, Fukai K, Imazeki F, Muramatsu M, Seki N, Miyazaki M, Ochiai T, Hirasawa H, et al: Serum osteopontin levels in patients with acute liver dysfunction. Scand J Gastroenterol. 41:102–110. 2006. View Article : Google Scholar : PubMed/NCBI
18	Sarin SK, Kedarisetty CK, Abbas Z, Amarapurkar D, Bihari C, Chan AC, Chawla YK, Dokmeci AK, Garg H, Ghazinyan H, et al: APASL ACLF Working Party: Acute-on-chronic liver failure: Consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014. Hepatol Int. 8:453–471. 2014. View Article : Google Scholar : PubMed/NCBI
19	Tang CM, Yau TO and Yu J: Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments. World J Gastroenterol. 20:6262–6278. 2014. View Article : Google Scholar : PubMed/NCBI
20	Graupera I, Solà E, Fabrellas N, Moreira R, Solé C, Huelin P, de la Prada G, Pose E, Ariza X, Risso A, et al: Urine Monocyte Chemoattractant Protein-1 Is an Independent Predictive Factor of Hospital Readmission and Survival in Cirrhosis. PLoS One. 11:e01573712016. View Article : Google Scholar : PubMed/NCBI
21	Duarte-Salles T, Misra S, Stepien M, Plymoth A, Muller D, Overvad K, Olsen A, Tjønneland A, Baglietto L, Severi G, et al: Circulating osteopontin and prediction of hepatocellular carcinoma development in a large European population. Cancer Prev Res (Phila). 9:758–765. 2016. View Article : Google Scholar : PubMed/NCBI
22	Rastogi A, Bihari C, Maiwall R, Ahuja A, Sharma MK, Kumar A and Sarin SK: Hepatic stellate cells are involved in the pathogenesis of acute-on-chronic liver failure (ACLF). Virchows Arch. 461:393–398. 2012. View Article : Google Scholar : PubMed/NCBI
23	Shih SC, Ho TC, Chen SL and Tsao YP: Pigment epithelium-derived factor (PEDF) peptide promotes the expansion of hepatic stem/progenitor cells via ERK and STAT3-dependent signaling. Am J Transl Res. 9:1114–1126. 2017.PubMed/NCBI
24	Wang G, Zhao C, Chen S, Li X, Zhang L, Chang C and Xu C: A preliminary in vivo study of the effects of OPN on rat liver regeneration induced by partial hepatectomy. Mol Biol Rep. 43:1371–1382. 2016. View Article : Google Scholar : PubMed/NCBI
25	Urtasun R, Lopategi A, George J, Leung TM, Lu Y, Wang X, Ge X, Fiel MI and Nieto N: Osteopontin, an oxidant stress sensitive cytokine, up-regulates collagen-I via integrin α(V)β(3) engagement and PI3K/pAkt/NFκB signaling. Hepatology. 55:594–608. 2012. View Article : Google Scholar : PubMed/NCBI
26	Wang X, Lopategi A, Ge X, Lu Y, Kitamura N, Urtasun R, Leung TM, Fiel MI and Nieto N: Osteopontin induces ductular reaction contributing to liver fibrosis. Gut. 63:1805–1818. 2014. View Article : Google Scholar : PubMed/NCBI
27	Coombes JD, Swiderska-Syn M, Dollé L, Reid D, Eksteen B, Claridge L, Briones-Orta MA, Shetty S, Oo YH, Riva A, et al: Osteopontin neutralisation abrogates the liver progenitor cell response and fibrogenesis in mice. Gut. 64:1120–1131. 2015. View Article : Google Scholar : PubMed/NCBI
28	Strazzabosco M, Fabris L and Albano E: Osteopontin: A new player in regulating hepatic ductular reaction and hepatic progenitor cell responses during chronic liver injury. Gut. 63:1693–1694. 2014. View Article : Google Scholar : PubMed/NCBI
29	Uede T: Osteopontin, intrinsic tissue regulator of intractable inflammatory diseases. Pathol Int. 61:265–280. 2011. View Article : Google Scholar : PubMed/NCBI
30	Inoue M and Shinohara ML: Intracellular osteopontin (iOPN) and immunity. Immunol Res. 49:160–172. 2011. View Article : Google Scholar : PubMed/NCBI
31	Nagoshi S: Osteopontin: Versatile modulator of liver diseases. Hepatol Res. 44:22–30. 2014. View Article : Google Scholar : PubMed/NCBI