Published online Jul 18, 2015. doi: 10.4254/wjh.v7.i14.1875
Peer-review started: April 24, 2015
First decision: May 13, 2015
Revised: May 29, 2015
Accepted: June 30, 2015
Article in press: July 2, 2015
Published online: July 18, 2015
AIM: To assess serum cartilage oligomeric matrix protein (COMP) as a marker of cirrhosis and risk of progression to hepatocellular carcinoma (HCC).
METHODS: A COMP enzyme-linked immunosorbent assay was used to test 187 patients with chronic liver diseases at the time point of first evaluation. The selected patients included 72 with chronic hepatitis B infection, 75 with chronic hepatitis C infection, 22 with primary biliary cirrhosis, 7 with autoimmune hepatitis type 1, and 11 with alcoholic liver disease. Demographic, biochemical, histological and clinical characteristics of the patients were recorded at the first evaluation. One hundred and forty-seven patients were followed for a median [interquartile range (IQR)] duration of 96.5 (102) mo. The clinical, biochemical and histological data, as well as the development of cirrhosis, HCC according to internationally accepted criteria and in case of death, a liver-related cause during the follow-up period, were recorded at the electronic database of our clinic. COMP determination was also performed in 43 healthy individuals who served as the control study group.
RESULTS: COMP positivity (> 15 U/L) was detected in 22%-36% among chronic liver disease groups. Strikingly, almost 83% of COMP-positive patients were cirrhotic at baseline, independently of cause of liver disease. Among the patients who developed HCC during follow-up, 73.7% (14/19) were COMP positive at baseline. COMP positivity was significantly associated with older age (P < 0.001), advanced fibrosis (P = 0.001) and necroinflammatory activity (P = 0.001), higher aspartate aminotransferase (P < 0.001), alanine aminotransferase (P < 0.02), γ-glutamyl transpeptidase (P = 0.003), alkaline phosphatase (P = 0.001), bilirubin (P < 0.05), international normalized ratio (P = 0.002) and alpha-fetoprotein levels (P < 0.02), and lower albumin (P < 0.001), and platelet count (P = 0.008). COMP levels [median (IQR)] were significantly higher in cirrhotics compared to non-cirrhotics [13.8 (7.9) U/L vs 9.8 (4.6) U/L, respectively; P < 0.001]. On multivariate logistic regression analysis, COMP-positivity was independently associated only with cirrhosis (OR = 4.40, 95%CI: 1.33-14.69, P = 0.015). Kaplan-Meier analysis showed that COMP positivity was significantly associated with HCC development (P = 0.007) and higher incidence of liver-related death (P < 0.001).
CONCLUSION: Elevated COMP levels are strongly associated with cirrhosis and HCC progression. Serum COMP is a new promising non-invasive biomarker for HCC risk assessment in surveillance programs.
Core tip: We report our first results regarding the utility of serum cartilage oligomeric matrix protein (COMP), an antigen over-expressed in developing liver, as a novel non-invasive marker of liver fibrosis and risk of progression to hepatocellular carcinoma (HCC). HCC is the third leading cause of cancer deaths worldwide, therefore non-invasive tests of fibrosis, as well as tests that can predict which patients are at high risk to develop HCC are needed. Our results suggest that COMP levels are associated with cirrhosis and a worse prognosis, thus serum COMP may assist clinicians as a non-invasive biomarker for risk assessment in surveillance programs.