COMP serum levels: A new non-invasive biomarker of liver fibrosis in patients with chronic viral hepatitis

Published:January 15, 2017DOI:


      • Cartilage oligomeric matrix protein (COMP) is proposed as marker of liver fibrosis.
      • COMP levels are comparable with histology, transient elastography (TE), APRI, FIB-4.
      • COMP detects cirrhosis with the same accuracy as TE, APRI and FIB-4.
      • COMP measurements are not affected by inflammation and need no special equipment.
      • COMP is a sensitive, non-invasive, reproducible, low cost marker of liver fibrosis.


      Background & aims

      Recently we have shown that cartilage oligomeric matrix protein (COMP), a fibrillar collagen assembly regulator, is strongly associated with cirrhosis and hepatocellular carcinoma progression. Therefore, we assessed whether serum COMP levels can be used as a non-invasive fibrosis marker in patients with chronic viral hepatitis (CVH) and compared this marker with standard methods for disease stage assessment [histology, transient elastography (TE), APRI, FIB-4].


      Sera from 116 CVH patients, 66 HBV [24 female; median age 53(22–76)] and 50 HCV [21 female; median age 48.5(25–69)] were investigated by COMP-ELISA. APRI and FIB-4 score was calculated in all along with TE. Liver biopsy was performed in 61. Patients were divided into two groups (F1/F2 and F3/F4) according to Metavir score.


      55/116 (47%) CVH patients were classified in F3/F4-group according to TE [14.3(9.3–75) kPa]. APRI score was >1.5 in 21/116 and FIB-4 > 3.25 in 20/116. Liver histology revealed 24/61 (39%) patients with significant fibrosis (stage 3–4), while 12/61 (19.7%) had cirrhosis. COMP levels correlated with TE measurements (r = 0.5; p < 0.001) and APRI score (r = 0.23; p < 0.02). The diagnostic accuracy of COMP in detecting cirrhosis was as good as TE, APRI and FIB-4 index (AUC 0.884) with sensitivity and specificity of 83.3% and 83.7% (cut-off 11.5 U/L).


      COMP serum levels performed as well as TE, APRI and FIB4 score in detecting cirrhosis in CVH patients, suggesting COMP as a sensitive non-invasive, easy to perform biomarker of liver fibrosis. Further studies are needed in order to validate our findings in CVH patients.


      ECM (extracellular matrix), CVH (chronic viral hepatitis), CHB (chronic hepatitis B), CHC (chronic hepatitis C), TE (transient elastography), LSM (liver stiffness measurement), COMP (cartilage oligomeric matrix protein), HCC (hepatocellular carcinoma), RA (rheumatoid arthritis), OA (osteoarthritis), SSc (systemic sclerosis), AST (aspartate aminotransferase), APRI (AST to Platelet Ratio Index), FIB-4 (Fibrosis-4 score), IQR (interquartile range), PLT (platelets), SD (standard deviation), MWU (Mann-Whitney U test), ANOVA (analysis of variance), ROC (receiver operating characteristic), AUC (area under the curve), aFP (alpha fetoprotein), ALP (alkaline phosphatase), ALT (alanine aminotransferase), PPV (positive predictive value), NPV (negative predictive value)


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