Plasma tissue inhibitor of metalloproteinases-1 and transforming growth factor beta 1--possible non-invasive biomarkers of hepatic fibrosis in patients with chronic B and C hepatitis.
OBJECTIVE
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.


METHODS
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. TIMP-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 = 0.71) 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.
Flisiak
Robert
R
Department of Infectious Diseases, Liver Unit Medical Academy of Bialystok, Zurawia Str., 14, Bialystok 15-540, Poland. flisiakr@priv.onet.pl
Maxwell
Paul
P
Prokopowicz
Danuta
D
Timms
Peter M
PM
Panasiuk
Anatol
A
D000328:Adult; D015415:Biomarkers; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000097:blood*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis*; D008297:Male; D012698:Serologic Tests; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D016212:Transforming Growth Factor beta / Q000097:blood*
D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta