EVA DATION OF LIVER FIBROSIS MARKERS IN CHRONIC LIVER DISEASES

Abstract

Liver fibrosis is a dynamic bi-directional process involving phases of progression and regression. Its diagnosis is dependent on histopathological examination of biopsy specimens. Non invasive serum markers of liver fibrosis would be of great clinical benefit as they would allow repeated assessment, with avoidance of the invasiveness of liver biopsy with its complications. This study was carried out on 50 patients (43males and 7 females) with chronic liver disease from the Hepatology ,Gastroenterology and Infectious diseases department of Banha University Hospitals and 10 healthy subjects as a control group. For both groups; estimation of serum matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-I) and haptoglobin was done. Scoring of the age-platelet index (API) and AST to platelet ratio index (APRI) was also done for the patients group, and finally, liver biopsy with histopathological examination for the necroinflammatory grade (A) and fibrosis stage (F) applying the METAVIR scoring system. Results showed that the mean serum levels of MMP-9 were significantly higher in patients than in controls (p<0.05) and showed a significant negative correlation with METAVIR grade (p<0.05). By using ROC curves to assess MMP-9 for discrimination of significant fibrosis (F2'::2) and cirrhosis (F4), the AUROC were 0.67±0.17 and 0.69±0.18 respectively. The mean values of serum TIMP-1 were significantly higher in patients than in controls (p<0.05), with non significant positive correlation with fibrosis progression (p>0.05), while it showed a significant increase (p<0.05) with METAVIR grades (A). AUROC for F 2':: 2 and F4 were 0.58 ± 0.2 and 0.53 ± 0.19 respectively, while for A 2':: 2, it was 0.67 ± 0.17. Haptoglobin levels were non significantly lower in patients than in controls (p>0.05) but showed a significant negative correlation with fibrosis progression (r=-0.4, p<0.05) and AUROC for F 2':: 2 and F4, were 0.75 ± 0.17 and 0.78± 0.15 respectively. To conclude, MMP-9 was a fair marker of fibrosis as well as necroinflammatory activity, and TIMP-1 was a sensitive and to a lesser extent specific marker of advanced liver disease, discriminating necroinflammatory activity rather than fibrosis stage. On the other hand, 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.