Diagnostic and prognostic significance of cell death and macrophage activation markers in patients with hepatocellular carcinoma

J Hepatol. 2013 Oct;59(4):769-79. doi: 10.1016/j.jhep.2013.06.008. Epub 2013 Jun 17.


Background & aims: The serum cell death parameters M30 and M65 and the macrophage activation marker sCD163 (soluble CD163) are elevated in patients with acute and chronic liver diseases. However, their diagnostic and prognostic potential in patients with hepatocellular carcinoma (HCC) has not yet been investigated.

Methods: Serum levels of M30, M65, and sCD163 were measured in two cohorts of HCC patients and a cohort of cirrhotic patients. The parameters were compared between patients with and without HCC and the overall survival (OS) times according to M30, M65, and sCD163 were assessed.

Results: M30 and M65 levels were higher in HCC patients than in cirrhotic patients (both p < 0.001). M65 was an independent parameter for non-invasive identification of HCC patients by logistic regression analysis and could supplement AFP (alpha-fetoprotein) and abdominal ultrasound in non-invasive detection of HCC patients. High M65 serum levels as well as high sCD163 concentrations were associated with an impaired prognosis in univariate Cox regression analysis. The sCD163 level was associated with OS independently of the CLIP (Cancer of the Liver Italian Program) score, the BCLC (Barcelona Clinic Liver Cancer) stage, and the CRP (C-reactive protein) level in a multivariate Cox regression model.

Conclusions: Serum M65 has the potential as a new diagnostic parameter for HCC and serum sCD163 is a new prognostic parameter in HCC patients.

Keywords: AFP; AUROC; BCLC; Barcelona Clinic Liver Cancer; C-reactive protein; CD163; CK; CLIP; CRP; Cancer of the Liver Italian Program; Cell death; ELISA; HCC; Hepatocellular carcinoma; LITT; M30; M65; MELD; NASH; OS; RFA; ROC; TACE; alpha-fetoprotein; area under the receiver operating curve; cytokeratin; enzyme-linked immunosorbent assay; hepatocellular carcinoma; laser interstitial thermal therapy; model of end stage liver disease; non-alcoholic steatohepatitis; overall survival; radiofrequency ablation; receiver operating curve; sCD163; soluble CD163; transarterial chemoembolisation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / blood*
  • Antigens, Differentiation, Myelomonocytic / blood*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / diagnosis
  • Case-Control Studies
  • Cell Death
  • Cohort Studies
  • Female
  • Humans
  • Keratin-18 / blood*
  • Liver Cirrhosis / blood
  • Liver Neoplasms / blood*
  • Liver Neoplasms / diagnosis
  • Macrophage Activation*
  • Male
  • Middle Aged
  • Peptide Fragments / blood*
  • Prognosis
  • Receptors, Cell Surface / blood*


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Biomarkers, Tumor
  • CD163 antigen
  • Keratin-18
  • M30 cytokeratin-18 peptide, human
  • M65 antigen, human
  • Peptide Fragments
  • Receptors, Cell Surface