Background and study aim: Chronic HCV can progress to cirrhosis, and HCC. Liver biopsy is the best to assess and monitor progression. But it has limitations.The aim of this study was to evaluate noninvasive indicators of fibrogenesis, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-1 (T1MP1) and AST/Platelet (APRI-score) for assessment of early hepatic histopathology in chronic-HCV, and cirrhosis. Patients and methods: A cross section study included 344 participants from Tanta University Hospitals, (GI): 129 asymptomatic chronic-HCV, (GII): 135 with symptoms. (GIII): 80 patients with compensated HCV-related cirrhosis and 30 healthy controls. Investigations proved diagnosis, and excluded associated diseases. APRI-Score was evaluated. Quantitative immunoassay measured serum MMP-2 and TIMP-1, guided liver biopsy for histopathology staging and grading. Results: Serum MMP-2& TIMP-1 showed significant difference between control& GI, GII, GIII, and GI, GII& GIII (P< 0.001) with significant correlation between GI& GIII, between GII & GIII, while insignificant between G1 & GII. There was significant positive correlation between APRI-score versus Metavir A, Metavir F, Ishak score of fibrosis, serum MMP-2 and serum TIMP-1 (P <0.001). Combined serum MMP-2, TIMP-1 and APRI-score showed high sensitivity, and specificity. Conclusion: This combination of markers raised the sensitivity, specificity and correlations. It could reflect early hepatic histopathology, developing cirrhosis and potentially could replace liver biopsies in pre-treatment, follow up of chronic-HCV, and screening of asymptomatic patients.