Evaluation of selected markers of liver fibrosis in chronic hepatitis C virus patients

ABSTRACT

To evaluate the usefulness of serum hyaluronan [HA], matrix rnetalloproteinase-9 [MMP-9] and tissue inhibitor of metalloproteinase-1 TIMP-1 as well as AST/ALT ratio [whether as isolated or combined variables] in discrimination of stages of fibrosis in chronic hepatitis C [CHC] patients. Internal Medicine, Medical Biochemistry and Pathology Departments, Faculty of Medicine, Cairo University and Internal Medicine Department. Theodor Research Institute. Thirty six patients with CHC and twelve age and sex-matched healthy subjects as a control group. Histological staging of fibrosis [F0. F1, F2, F3 and F4] was performed in liver biopsy specimen according to the METAVIR Score. Serum levels of HA, MMP-9 and TIMP-l were determined by the Enzyme Linked Immunosorbent Assay [ELISA]. The AST/ALT ratio was calculated. Levels of serum HA and TIMP-I were significantly increased in all stages of fibrosis versus the control group. The AST/ALT ratio was significantly increased while the MMP-9 was significantly decreased in the F2, F3 and F4 stages only versus the controls. Using receiver operating characteristic analysis, the area under the curve [AUC] of the score to discriminate extensive fibrosis [F3] and cirrhosis [F4] stages of CHC from early stages of CHC [FO. Fl, F2] were 0.98 for TIMP-1. with a sensitivity of' 100% and specificity 72.9% . As for HA, the AUC was 0.93% with a sensitivity of' l00f and specificity 57.8% . By multivariate regression analysis, only HA followed by TIMP-1 wee independently associated with extensive fibrosis and/or cirrhosis and were accurate in discriminating F3/F4 stages from the early F0/F1/F2 stages. Furthermore, a combination of the our studied parameters increased the accuracy. The present results suggest that the serum fibrotic markers, especially HA and TIMP-1, may be clinically useful in discriminating early fibrotic stages from the late extensive fibrosis and cirrhosis stages in patients with CHC, especially if combined with other variables, as MMP-9 and AST/ALT ratio