Effect of lamivudine treatment on plasma levels of transforming growth factor beta1, tissue inhibitor of metalloproteinases-1 and metalloproteinase-1 in patients with chronic hepatitis B.
OBJECTIVE
Transforming growth factor (TGF)- beta1, metalloproteinase (MMP)-1 and its tissue inhibitor (TIMP)-1 are considered predictive biomarkers of chronic hepatitis activity and fibrosis. The aim of this study was to evaluate the effect of lamivudine treatment on the plasma levels of these peptides in patients with chronic hepatitis B.


METHODS
TGF-beta1, MMP-1 and TIMP-1 plasma concentrations were measured with an enzyme immunoassay in 40 patients treated with lamivudine for 48 wk. Elimination of HBV-DNA and HBV antigens was evaluated 24 wk after treatment completion.


RESULTS
Baseline TGF-beta1 (29.6+/-2.2 ng/mL) and TIMP-1 (1 578+/-93 ng/mL) significantly exceeded normal values (18.3+/-1.6 ng/mL and 1 102+/-67 ng/mL respectively). Lamivudine treatment resulted in a significant decrease of TGF-beta1 and TIMP-1 during treatment with an increase after 24 wk of treatment. Pretreatment MMP-1 levels (6.7+/-0.7 ng/mL) were significantly lower than normal values (11.9+/-0.9 ng/mL) and increased during treatment and follow-up. A significant correlation was noted between TGF-beta1 or TIMP-1 and aminotransferases as well as fibrosis scored in liver biopsy specimens. There were no statistically significant differences of TGF-beta1, TIMP-1 and MMP-1 between four groups at baseline, 24 and 48 wk of treatment. TGF-beta1 and TIMP-1 levels increased significantly in non-responders and normalized in responders at wk 72. MMP-1 also normalized in responders and decreased to values significantly lower than normal in non-responders.


CONCLUSIONS
These findings support the role of TGF-beta1, TIMP-1 and MMP-1 in the pathogenesis of chronic hepatitis B. Because of their association with hepatic injury and antiviral treatment efficacy, determination of these peptides may be useful in disease management.
Flisiak
Robert
R
Department of Infectious Diseases, Medical University of Bialystok, Bialystok, Poland. flisiakr@priv.onet.pl
Al-Kadasi
Haza
H
Jaroszewicz
Jerzy
J
Prokopowicz
Danuta
D
Flisiak
Iwona
I
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1
D018894:Reverse Transcriptase Inhibitors; C508960:TGFB1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019259:Lamivudine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020781:Matrix Metalloproteinase 1