Diagnostic role of collagen-III and matrix metalloproteinase-1 for early detection of hepatocellular carcinoma.

Background: As the poor prognosis of hepatocellular carcinoma (HCC) is mostly due to late detection at an advanced stage there is a strong need for establishing more effective strategies for early identification. We hypothesized that collagen-III and matrix metalloproteinase-1 (MMP-1) and their ratio (CMR) are effective markers for identifying early-HCC when used alongside serum AFP, alkaline phosphatase and bilirubin.Methods: We recruited 148 patients with HCC, 133 with cirrhosis and 121 with fibrosis. Liver fibrosis was staged according to METAVIR, HCC was diagnosed by on histological findings or typical imaging characteristics by ultrasound and computed tomography. Collagen-III and MMP-1 were identified based on Western blotting and quantified in sera using ELISA, liver function tests (LFTs) by routine methods.Results: Patients with HCC showed a significantly (P < 0.05) higher collagen-III and collagen-III/MMP-1 ratio (CMR) than fibrotic and cirrhotic patients. Patients with HCC showed significantly (P < 0.05) lower concentration of MMP-1 than those without. As expected, numerous LFTs were also abnormal. A score of AFP, alkaline phosphatase and bilirubin together with CMR (the HCC-ABC test) was then constructed, This yielded ROC area under curves of 0.85 (95% CI 0.79-0.98) for identifying small tumour size (<3 cm), 0.87 (0.79-0.98) for identifying CLIP (0-1) [Cancer of the Liver Italian Program] disease severity, and 0.87 (0.74-0.93) for identifying BCLC disease severity (all p < 0.001), which is each case exceeded the predictive value of AFP.Conclusion: HCC-ABC diagnostic Test is a promising index for HCC early detection with a high degree of accuracy that may facilitate therapy.

A panel of a mitogenic (PDGF), biochemical (albumin) and demographic (age) parameters for the non-invasive assessment of hepatic fibrosis.

Background: Several studies have investigated certain fibrosis markers that incorporate liver function tests, fragments of liver-matrix components and/or degraded products generated by hepatic stellate cells for determining the degree of hepatic fibrosis. However, the role of these molecules in the development of hepatic fibrosis is unclear. This work aimed (a) to determine whether platelet-derived growth factor (PDGF) is linked to different stages of hepatic fibrosis and (b) investigate its diagnostic performance alongside other laboratory and demographic factors in assessing liver fibrosis in chronic hepatitis C infection. Methods: Liver-fibrosis was staged according to Fibroscan, PDGF quantified using ELISA, and liver function tests and other analytes determined by standard techniques in 239 patients with chronic hepatitis C virus infection. Results: Patients with significant (F2-F4), advanced fibrosis (F3-F4) and cirrhotic liver disease (F4) showed significantly (P<0.0001) higher PDGF levels increase respectively compared to stage F0/1. We used this to construct the PARA-Index (PDGF/albumin ratio, age), which performed well in assessing hepatic-fibrosis stages with AUCs of 0.91, 0.87 and 0.86 for identifying F2-F4, F3-F4 and F4, respectively. Additionally, the PARA-Index correlated strongly (r=0.65, P<0.0001) with the severity of the fibrosis. An elevated PARA-index provided odds ratios of 21.0, 20.7 and 10.3 for developing F2-F4, F3-F4 and F4, respectively. Conclusion: A panel of mitogenic (PDGF), biochemical (albumin) and demographical (age) parameters may improve liver-fibrosis staging with a high degree of accuracy in those with a hepatitis C virus infection.

Fibro-Mark: a panel of laboratory parameters for predicting significant fibrosis in chronic hepatitis C patients.

BACKGROUND: Fibrosis markers are useful for the prediction of cirrhosis but clinical scores such as King's score, AST-Platelet ratio index (APRI), Biotechnology research center (BRC), Fibrosis routine test (FRT), Fibro-α score and Fibro-quotient (FibroQ) have limited accuracy for diagnosing significant fibrosis. We hypothesised that new markers (reflecting the balance between hepatic fibrogenesis and fibrolysis) together with other indirect fibrosis markers would together construct a more sensitive and specific score capable of identifying fibrosis than existing scores. METHODS: Collagen IV, hyaluronic acid, platelet-derived growth factor (PDGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by ELISA, and AST, ALT, platelet count, albumin, total bilirubin, INR and AFP by routine methods in 148 patients with hepatitis C induced liver disease. Stepwise linear discriminant analysis and area under receiver-operating characteristic curves (AUCs) were used to create a predictive score and compare it to others. RESULTS: Patients with significant fibrosis (n = 100, F2-F4) showed 2.08, 2.14, 1.80 and 1.90-fold increase in collagen IV, hyaluronic acid, PDGF and TIMP-1, respectively, over patients with no or mild fibrosis (n = 48, F0/F1)(all p < 0.01). Significant independent predictors of F2-F4 were AFP (AUC 0.79), age (0.76), PDGF (0.74), collagen IV (0.78) and TIMP (0.75), which together formed a five-marker score 'Fibro-Mark' for predicting F2-F4. In comparison with other scores, AUC for Fibro-Mark was 0.89, BRC was 0.83, followed by FRT and King's score (both 0.82), APRI (0.80), Fibro-α (0.70) and finally Fibro Q (0.63). CONCLUSIONS: The Fibro-Mark score provides better discrimination in hepatic-fibrosis staging in chronic hepatitis C patients than existing scores.