Serum profiles of extracellular matrix degradation inhibitors across the stages of liver fibrosis in chronic hepatitis C patients

Abstract EN

Objective: Tissue inhibitor metalloproteinase-1 (TIMP-1) and alpha-2 macroglobulin (AMG) are extracellular matrix degradation inhibitors that have been demonstrated to increase with liver fibrosis.

1 lowever, data are lacking regarding their patterns of change.

This study analyses their detailed serum prollle across liver Fibrosis stages in chronic hepatitis C (CHC).

Methods: Serum TIMP-1 and AMG measurements were evaluated for 78 adult male CHC patients versus liver fibrosis (F) stages (Miri'AVlR FO-1'4).

rhe performance characteristics for discrimination of seqjuential (close stages), significant (l'>2), and advanced (F>3) fibrosis were assessed.

Results: Botli TIMP-1 and AMG correlated significantly with fibrosis (r=0.31, p=0.005; r=0.37, p==0.001, respectively), but failed to discriminate sequential stages.

For discrimination of significant fibrosis, the areas under receiver operating characteristics curves were small (0.59 and 0.57, respectively).

At a cut-off value of 743 ng/ml, riMP-1 showed a 100% specificity (with 17.6% sensitivity), while at a cut-off of 3 gm/1, AMG showed 73.5% sensitivity (with 36.4% specificity).

A similarly modest discrin)ination was noted for advanced fibrosis.

Interestingly, AMG showed an early rise with significantly higher values in FO compared with healthy controls (3.6±1.1 vs.

1.8-±0.6, respectively).Conclusions: Neither TIMP-1 nor AMG could discriminate the sequential stages of fibrosis.

Their modest perfonnances for discrimination of significant and advanced fibrosis are related to the wide normal range of TIMP-1 and the early rise of AMG.

A longitudinal monitoring would give a better understanding of their true changes, and examine whether patients having high AMG levels at FO would be fast fibrosers or respond differently to therapy.