Effect of antiviral therapy on markers of fibrogenesis in patients with chronic hepatitis C.
BACKGROUND
The possible markers of liver fibrosis (plasma YKL-40, PIIINP, MMP-2 and TIMP-1) were measured at the start (t0) and end of treatment (t12) with alpha-interferon and ribavirin and repeated at 6-months follow-up (t18) in 51 patients with chronic hepatitis C.


METHODS
We evaluated 1) whether treatment response is reflected by a decrease in these markers during antiviral therapy; 2) whether these markers reflect the activity of the disease; and 3) whether these markers could be used as predictors of the treatment response.


RESULTS
Baseline plasma YKL-40, MMP-2, PIIINP and TIMP-1 were significantly increased in patients compared to normal controls. In responders (n = 30), plasma YKL-40 (P < 0.05), MMP-2 (P < 0.05) and TIMP-1 (P < 0.001) decreased significantly at t18, and no changes were observed at t12. Plasma PIIINP was unchanged in responders. In non-responders (n = 19), plasma MMP-2 (P < 0.01) and TIMP-1 (P < 0.01) decreased significantly at t18, whereas plasma YKL-40 and PIIINP were unchanged. The markers were significantly correlated at baseline (P < 0.001). Plasma PIIINP at baseline could predict treatment response (P = 0.01).


CONCLUSIONS
Response to antiviral treatment is associated with a decrease in the fibrogenetic markers, but the markers do not reflect the biochemical disease activity during treatment. Baseline plasma PIIINP was the only marker predicting treatment response.
Nøjgaard
C
C
Dept. of Gastroenterology, H:S, Hvidovre Hospital, University of Copenhagen, Denmark. mille@dadlnet.dk
Johansen
J S
JS
Krarup
H B
HB
Holten-Andersen
M
M
Møller
A
A
Bendtsen
F
F
D054392:Adipokines; D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000187:drug effects*; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D037102:Lectins; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology / Q000276:immunology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000187:drug effects*; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects*; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood / Q000187:drug effects*; D012367:RNA, Viral; D012254:Ribavirin / Q000494:pharmacology* / Q000627:therapeutic use; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000187:drug effects*; D016896:Treatment Outcome
D054392:Adipokines; D000998:Antiviral Agents; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D016898:Interferon-alpha; D037102:Lectins; D010446:Peptide Fragments; D011347:Procollagen; D012367:RNA, Viral; D019715:Tissue Inhibitor of Metalloproteinase-1; C041876:procollagen Type III-N-terminal peptide; D012254:Ribavirin; D020778:Matrix Metalloproteinase 2