Circulating Survivin and TIMP-1 in Hepatitis C Virus Associated Liver Fibrosis

Abstract

Aims: The present study was conducted to assess the clinical utility of survivin, an anti-apoptotic protein, and the profibrogenic tissue inhibitor metalloproteinase-1 (TIMP-1) as non-invasive biomarkers for the discrimination between stages of HCV-associated liver fibrosis that are largely asymptomatic. Methodology: Circulating survivin and TIMP-1 levels as well as their corresponding proteins and genes expressions were, respectively, assessed by ELISA, Western blot and RT-PCR in 100 HCV-infected patients at different stages of liver fibrosis in comparison to healthy controls. Results: With the progression of hepatic fibrosis, each of circulating survivin and TIMP-1 as well as their ratio (survivin/TIMP-1) showed a stepwise increase and exhibited significant positive correlations with the fibrotic stage (r=0.98 & p=0.002, r=0.95 & p=0.01, and r=0.93 & p=0.013 respectively). A gradual increase in both survivin and TIMP-1 genes expression was also observed. Conclusion: In conclusion, survivin, TIMP-1, and their ratio could represent promising biomarkers for prediction and discrimination of different stages of HCV-associated liver fibrosis. The higher sensitivity and specificity of survivin may provide new insights into its possible use as a target for the antifibrotic drugs. Further studies with validated tests on a large scale prospective clinical trial are required to ascertain these results.