Skip to main content

Advertisement

SpringerLink
Log in

Macrophage-related serum biomarkers soluble CD163 (sCD163) and soluble mannose receptor (sMR) to differentiate mild liver fibrosis from cirrhosis in patients with chronic hepatitis C: a pilot study

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Macrophages regulate the fibrotic process in chronic liver disease. The aim of the present pilot study was to evaluate two new macrophage-specific serum biomarkers [soluble CD163 (sCD163) and soluble mannose receptor (sMR, sCD206)] as potential fibrosis markers in patients chronically infected with hepatitis C virus (HCV). Forty patients with chronic hepatitis C were included from two hospital clinics. On the day of inclusion, transient elastography (TE) was performed to assess the fibrosis stage, and blood samples were collected for the measurement of sCD163 and sMR. The plasma concentrations of both biomarkers were significantly higher in patients infected with HCV and with cirrhosis compared to those with no/mild liver fibrosis (5.77 mg/l vs. 2.49 mg/l and 0.44 mg/l vs. 0.30 mg/l for sCD163 and sMR, respectively). The best separation between groups was obtained by sCD163 [area under the receiver operating characteristic curve (AUC) 0.89 (95 % confidence interval [CI] 0.79–0.99)] as compared to sMR [AUC 0.75 (95 % CI 0.61–0.90)]. sCD163 and sMR correlated significantly (r 2 = 0.53, p < 0.0001). Interestingly, sCD163 also correlated significantly with TNF-α (presented in a previous publication), which is shed to serum by the same mechanism as sCD163 (r 2 = 0.40, p < 0.0001). In conclusion, the macrophage-related markers sCD163 and sMR are significantly higher in patients chronically infected with HCV and with cirrhosis than in those with no/mild fibrosis. sCD163 is a promising new fibrosis marker in patients infected with HCV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Adams LA (2011) Biomarkers of liver fibrosis. J Gastroenterol Hepatol 26:802–809

    Article  PubMed  Google Scholar 

  2. Castera L (2012) Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology 142:1293–1302

    Article  PubMed  Google Scholar 

  3. Van Thiel DH, Gavaler JS, Wright H, Tzakis A (1993) Liver biopsy: its safety and complications as seen at a liver transplant center. Transplantation 55:1087–1090

    Article  PubMed  Google Scholar 

  4. McGill DB, Rakela J, Zinsmeister AR, Ott BJ (1990) A 21-year experience with major hemorrhage after percutaneous liver biopsy. Gastroenterology 99:396–400

    Google Scholar 

  5. Regev A, Berho M, Jeffers LJ, Milikowski C, Molina EG, Pyrsopoulos NT, Feng ZZ, Reddy KR, Schiff ER (2002) Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol 97:2614–2618

    Article  PubMed  Google Scholar 

  6. Bedossa P, Dargère D, Paradis V (2003) Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 38:1449–1457

    PubMed  Google Scholar 

  7. Grønbaek K, Christensen PB, Hamilton-Dutoit S, Federspiel BH, Hage E, Jensen OJ, Vyberg M (2002) Interobserver variation in interpretation of serial liver biopsies from patients with chronic hepatitis C. J Viral Hepat 9:443–449

    Article  PubMed  Google Scholar 

  8. Ganne-Carrié N, Ziol M, de Lédinghen V, Douvin C, Marcellin P, Castéra L, Dhumeaux D, Trinchet JC, Beaugrand M (2006) Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases. Hepatology 44:1511–1517

    Article  PubMed  Google Scholar 

  9. Foucher J, Chanteloup E, Vergniol J, Castéra L, Le Bail B, Adhoute X, Bertet J, Couzigou P, de Lédinghen V (2006) Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut 55:403–408

    Article  CAS  PubMed  Google Scholar 

  10. Friedrich-Rust M, Ong MF, Martens S, Sarrazin C, Bojunga J, Zeuzem S, Herrmann E (2008) Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology 134:960–974

    Article  PubMed  Google Scholar 

  11. Ziol M, Handra-Luca A, Kettaneh A, Christidis C, Mal F, Kazemi F, de Lédinghen V, Marcellin P, Dhumeaux D, Trinchet JC, Beaugrand M (2005) Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology 41:48–54

    Article  PubMed  Google Scholar 

  12. Wynn TA, Barron L (2010) Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis 30:245–257

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Møller HJ, Peterslund NA, Graversen JH, Moestrup SK (2002) Identification of the hemoglobin scavenger receptor/CD163 as a natural soluble protein in plasma. Blood 99:378–380

    Article  PubMed  Google Scholar 

  14. Rødgaard-Hansen S, Rafique A, Christensen PA, Sandahl T, Maniecki M, Nexø E and Møller HJ (2013) A soluble form of the macrophage related mannose receptor (MR/CD206) is present in human serum and elevated in critical illness. Submitted for publication

  15. Gazi U, Rosas M, Singh S, Heinsbroek S, Haq I, Johnson S, Brown GD, Williams DL, Taylor PR, Martinez-Pomares L (2011) Fungal recognition enhances mannose receptor shedding through dectin-1 engagement. J Biol Chem 286:7822–7829

    Article  CAS  PubMed  Google Scholar 

  16. Hintz KA, Rassias AJ, Wardwell K, Moss ML, Morganelli PM, Pioli PA, Givan AL, Wallace PK, Yeager MP, Guyre PM (2002) Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163. J Leukoc Biol 72:711–717

    CAS  PubMed  Google Scholar 

  17. Grønbaek H, Sandahl TD, Mortensen C, Vilstrup H, Møller HJ, Møller S (2012) Soluble CD163, a marker of Kupffer cell activation, is related to portal hypertension in patients with liver cirrhosis. Aliment Pharmacol Ther 36:173–180

    Article  PubMed  Google Scholar 

  18. Andersen ES, Ruhwald M, Moessner B, Christensen PB, Andersen O, Eugen-Olsen J, Weis N (2011) Twelve potential fibrosis markers to differentiate mild liver fibrosis from cirrhosis in patients infected with chronic hepatitis C genotype 1. Eur J Clin Microbiol Infect Dis 30:761–766

    Article  CAS  PubMed  Google Scholar 

  19. Møller HJ, Hald K, Moestrup SK (2002) Characterization of an enzyme-linked immunosorbent assay for soluble CD163. Scand J Clin Lab Invest 62:293–299

    Article  PubMed  Google Scholar 

  20. Hanley JA, McNeil BJ (1983) A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiol 148:839–843

    CAS  Google Scholar 

  21. Dennis C (2001) Haemoglobin scavenger. Nature 409:141

    Article  CAS  PubMed  Google Scholar 

  22. Martinez-Pomares L (2012) The mannose receptor. J Leukoc Biol 92:1177–1186

    Article  CAS  PubMed  Google Scholar 

  23. Etzerodt A, Maniecki MB, Møller K, Møller HJ, Moestrup SK (2010) Tumor necrosis factor alpha-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163. J Leukoc Biol 88:1201–1205

    Article  CAS  PubMed  Google Scholar 

  24. Heymann F, Trautwein C, Tacke F (2009) Monocytes and macrophages as cellular targets in liver fibrosis. Inflamm Allergy Drug Targets 8:307–318

    Article  CAS  PubMed  Google Scholar 

  25. Porcheray F, Viaud S, Rimaniol AC, Léone C, Samah B, Dereuddre-Bosquet N, Dormont D, Gras G (2005) Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol 142:481–489

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Møller HJ, Grønbaek H, Schiødt FV, Holland-Fischer P, Schilsky M, Munoz S, Hassanein T, Lee WM; U.S. Acute Liver Failure Study Group (2007) Soluble CD163 from activated macrophages predicts mortality in acute liver failure. J Hepatol 47:671–676

    Article  PubMed Central  PubMed  Google Scholar 

  27. Holland-Fischer P, Grønbæk H, Sandahl TD, Moestrup SK, Riggio O, Ridola L, Aagaard NK, Møller HJ, Vilstrup H (2011) Kupffer cells are activated in cirrhotic portal hypertension and not normalised by TIPS. Gut 60:1389–1393

    Article  CAS  PubMed  Google Scholar 

  28. Hiraoka A, Horiike N, Akbar SM, Michitaka K, Matsuyama T, Onji M (2005) Soluble CD163 in patients with liver diseases: very high levels of soluble CD163 in patients with fulminant hepatic failure. J Gastroenterol 40:52–56

    Article  CAS  PubMed  Google Scholar 

  29. Ye H, Wang LY, Zhao J, Wang K (2013) Increased CD163 expression is associated with acute-on-chronic hepatitis B liver failure. World J Gastroenterol 19:2818–2825

    Article  PubMed  Google Scholar 

  30. Waidmann O, Brunner F, Herrmann E, Zeuzem S, Piiper A, Kronenberger B (2013) Macrophage activation is a prognostic parameter for variceal bleeding and overall survival in patients with liver cirrhosis. J Hepatol 58:956–961

    Article  PubMed  Google Scholar 

  31. Strader DB, Wright T, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases (2004) AASLD practice guideline: diagnosis, management, and treatment of hepatitis C. Hepatology 39:1147–1171

    Article  PubMed  Google Scholar 

  32. Sagir A, Erhardt A, Schmitt M, Häussinger D (2008) Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage. Hepatology 47:592–595

    Article  CAS  PubMed  Google Scholar 

  33. Arena U, Vizzutti F, Corti G, Ambu S, Stasi C, Bresci S, Moscarella S, Boddi V, Petrarca A, Laffi G, Marra F, Pinzani M (2008) Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology 47:380–384

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank laboratory technician Kirsten Bank Petersen for the excellent technical assistance, professor, DMSci, Jens Ole Nielsen for the framework and valuable advice, and biostatistician Steen Ladelund for the important assistance with the statistical analyses. The study was supported by the Danish Council for Strategic Research (TRAIN 10-092797) (Holger Jon Møller). The A.P. Moeller Foundation for the Advancement of Medical Science and the Danish Agency for Science, Technology and Innovation supported this study (grant support to Nina Weis).

Conflict of interest

Nina Weis is a member of an advisory board for Bristol-Myers Squibb Co., Merck Sharp Dohme Ltd., Janssen Cilag A/S and Gilead Sciences Inc., a teaching consultant for Roche A/S and Bristol-Myers Squibb Co., and a clinical investigator for Bristol-Myers Squibb Co., Janssen Cilag A/S, Merck Sharp Dohme Ltd. and Abbvie A/S. Belinda Moessner has received an unrestricted research grant from Roche A/S. Peer Brehm Christensen has been a member of the advisory board for Roche A/S and has received research grants from Roche A/S and Scheering-Plough A/S. Roche A/S provided the FibroScan equipment used in this study. Aarhus University holds patent applications with Holger Jon Møller and Sidsel Rødgaard-Hansen as co-inventors for the use of sCD163 and sMR in liver disease.

Author information

Authors and Affiliations

  1. Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark

    E. S. Andersen & Nina Weis

  2. Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    E. S. Andersen

  3. Department of Clinical Biochemistry, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus C, Denmark

    S. Rødgaard-Hansen & H. J. Møller

  4. Department of Infectious Diseases, Odense University Hospital, Odense, Denmark

    B. Moessner & P. B. Christensen

  5. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Nina Weis

Authors
  1. E. S. Andersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Rødgaard-Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Moessner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. B. Christensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. J. Møller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nina Weis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. J. Møller.

Additional information

Ellen Sloth Andersen and Sidsel Rødgaard-Hansen have shared first authorship.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andersen, E.S., Rødgaard-Hansen, S., Moessner, B. et al. Macrophage-related serum biomarkers soluble CD163 (sCD163) and soluble mannose receptor (sMR) to differentiate mild liver fibrosis from cirrhosis in patients with chronic hepatitis C: a pilot study. Eur J Clin Microbiol Infect Dis 33, 117–122 (2014). https://doi.org/10.1007/s10096-013-1936-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-013-1936-3

Keywords

Search

Navigation