Matrix metalloproteinases and their tissue inhibitors in children with chronic hepatitis B treated with lamivudine.
OBJECTIVE
To evaluate if measurements of MMP-2, MMP-9, TIMP-1 and TIMP-2 have clinical applicability as markers of liver fibrosis and to assess the effect of long-term lamivudine treatment on liver fibrosis in children with chronic hepatitis B (chB).


METHODS
The observation was carried out on 41 children with biopsy proven chB (HBe/+/, HBVDNA/+/) who were nonresponders to previous IFNalpha therapy. Lamivudine was administered in the group of 29 children (3 mg/kg/day, maximum 100 mg/daily). The serum concentration of examined markers was measured with ELISA before and after 24 months of therapy. ROC analysis was used to calculate the power of the assays to detect advanced liver fibrosis (score >2 according to Batts & Ludwig).


RESULTS
Serum TIMP-1 and TIMP-2 levels were significantly higher and MMP-9 lower in children with chB compared to controls. There was a significant positive correlation between serum MMP-2 and negative correlation between MMP-9 level and the stage of liver fibrosis. The ability of serum MMP-9 to differentiate children with mild fibrosis from those with advanced fibrosis was significant (AUC = 0.75; p = 0.03). Other serum markers did not allow a useful prediction. 2-year lamivudine treatment did not improve histological fibrosis but it caused significant decrease of serum TIMP-2 (p = 0.01) and increase of MMP-9 level (p = 0.00005).


CONCLUSIONS
MMP-9 is a better serum fibrosis marker than MMP-2, TIMP-1 and TIMP-2 to diagnose children with advanced liver fibrosis. The significant decrease of TIMP-2 and increase of MMP-9 level during therapy suggest antifibrotic effect of lamivudine in children with chB.
Lebensztejn
D M
DM
III Department of Pediatrics, Medical University of Białystok, Poland. DariuszMar.8810735@pharmanet.com.pl
Skiba
E
E
Sobaniec-Łotowska
M E
ME
Kaczmarski
M
M
D000293:Adolescent; D000998:Antiviral Agents / Q000494:pharmacology; D001706:Biopsy; D002648:Child; D005260:Female; D005355:Fibrosis; D006509:Hepatitis B / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D008099:Liver / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D012372:ROC Curve; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis
D000998:Antiviral Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019259:Lamivudine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9