Plasma tissue inhibitor of metalloproteinases-1 and transforming growth factor β1 -: Possible non-invasive biomarkers of hepatic fibrosis in patients with chronic B and C hepatitis

Background/Aims: The role of transforming growth factor-beta(1) (TGF-beta(1)) in liver fibrosis is,in part related to impairment of extracellular matrix breakdown by stimulation of tissue inhibitor of metalloproteinases-1 (TIMP-1),gene. The aim of the study was to evaluate association between TGF-beta(1) and TIMP-1 in relation to liver injury in chronic viral hepatitis B and C. Methodology: Association between plasma TGF-beta(1) and TIMP-1 was evaluated in 28 consecutive patients undergoing liver biopsy for chronic,viral hepatitis B and C (CH-B, CH-C) and these tests were correlated with hepatic fibrosis;, inflammation and liver function tests. Moreover carboxyterminal cross-linked telopeptide of type, 1,procollagen (ICTP) and carboxyterminal propeptide of type 1 collagen (PICP) were also measured for assessment of extracellular matrix breakdown or, synthesis, respectively. Results: Chronic viral hepatitis, B and C resulted in a significant increase in plasma TIMP-1 levels but not TGF-beta(1). Among biochemical markers of liver injury, significant correlation with TGF-beta(1) and TIMP-1 was,demonstrated in respect to aminotransferase activities in both groups. TlMP-1 showed significant correlation with ICTP levels in both CH-B (r=0.59) and CH-C (r=0.62), whereas TGF-beta(1) was correlated with ICTP, only in CH-C patients (r=0.75). PICP did not demonstrate, any correlation with either TGF-beta(1) or TIMP-1. Hepatic fibrosis, but not inflammation, correlated significantly with TGF-beta(1) (CH-B: r=0.73; CH-C: r=0.79) and TIMP-1 (CH-B: r=0.66; CH-C: r=10.71) in both groups and there was a significant correlation between TIMP-1 and TGF-beta(1) in the CH-B group (r=0.83) and CH-C group (r=79). Conclusions: These results support the role of TIMP-1 in a. TGF-beta(1)-dependent mechanism for liver fibrosis and suggest their plasma levels can be used as a possible early,non-invasive marker,of liver fibrosis useful for chronic hepatitis management.