Background: Liver fibrosis is a dynamic bi-directional process involving phases of progression and regression. Its diagnosis is dependent on histopathological examination of biopsy specimens. The aim of this study was to evaluate some non invasive serum markers of liver fibrosis and to correlate them with liver biopsy. Methods: Fifty patients with chronic liver diseases matched with 10 age and sex healthy blood donors were included in the study. For both groups; estimation of serum matrix metalloproteinase 9(MMP-9),tissue inhibitor of metalloproteinase 1(TIMP-1) by ELISA technique and haptoglobin by RID, scoring of the age-platelet index(API), AST to platelet ratio index(APRI),and prothrompin time (PT) were done. For the patients, histopathological examination of liver biopsy specimens for assessment of necroinflammatory grade (A) and fibrosis stage (F) applying the METAVIR scoring system. Results: API showed a significant positive correlation with both fibrosis and necroinflammatory activity , by using ROC curve for discrimination of significant fibrosis (F> 2) & moderate to severe necroinflammatory activity (A> 2), the AUROCs were 0.88 + 0.09 & 0.69 + 0.16 respectively. In case of Platelet count the AUROC was 0.80+ 0.12 for the diagnosis of established cirrhosis (F4). PT showed a significant positive correlation with fibrosis progression, and it was a sensitive predictor of significant fibrosis and the AUROCs, for(F > 2) and (F4) were 0.67+ 0.15 and 0.76 + 0.15 respectively . While APRI showed a significant positive correlation with both fibrosis stage and necroinflammatory grade and the AUROCs were 0.68+ 0.15 and 0.69 + 0.15, for (F > 2) and (F4) respectively .The mean serum level of MMP-9 was significantly higher in patients than controls(P < 0.05) and showed a significant negative correlation with fibrosis stage (P < 0.05). By using ROC curve to assess MMP-9 for discrimination of significant fibrosis (F> 2) and cirrhosis (F4), the AUROCs were 0.67+0.17 and 0.69+0.18 respectively, while for (A> 2), it was0.75+0.16. The mean value of serum TIMP-1 was significantly higher in patients than controls (P < 0.05), with significant positive correlation with necroinflammatory grade(P < 0.05). The AUROCs for (F> 2) and (F4) were 0.58+ 0.2 and 0.53+ 0.19 respectively, while for (A> 2), it was 0.67+0.17. Haptoglobin showed a significant negative correlation with fibrosis progression(r=-0.4, P < 0.05) and AUROC for(F> 2) and (F4) were 0.75+ 0.17 and 0.78+ 0.15 respectively. Conclusion: MMP-9 was a fair marker of fibrosis as well as inflammatory activity, and TIMP-1 was a sensitive and to a lesser extent specific marker of advanced liver disease, discriminating inflammatory activity rather than fibrosis stage. On the other hand API was the best marker that can discriminate significant fibrosis, while platelet count for diagnosis of cirrhosis. Among the assessed serum markers, haptoglobin, API and PT were the most sensitive predictors of significant fibrosis, while haptoglobin and API were the most sensitive predictors of cirrhosis. Finally , these serum assays, although promising, are still in need of being refined with further prospective studies. |
