Soluble adhesion molecules correlate with liver inflammation and fibrosis in chronic hepatitis C treated with interferon-alpha.
BACKGROUND
In chronic hepatitis C the relation of circulating adhesion molecules to disease features before, during and after therapy has not been completely established.


OBJECTIVE
To analyse the basal levels of circulating adhesins and the changes induced by interferon in these patients.


METHODS
We studied, using ELISA assays, the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in 52 patients with chronic hepatitis C on entry, prior to finalizing a 6-month course of interferon-alpha therapy and at the end of the follow-up. Correlations with clinical, virological and histological features, including inflammation and fibrosis, were calculated by Pearson's r-test.


RESULTS
Liver necroinflammation was more closely related to sICAM-1 (r = 0.54, P = 0.0000) than to sVCAM-1 (r = 0.32, P = 0.02). Fibrosis, both as serum pIIIP and histological scoring, was, however, clearly related to sVCAM-1 (1071+/-291 in patients who scored 0-2 vs. 1870+/-458 in patients who scored 3-4; P = 0.0000). Severe fibrosis was never found below a sVCAM-1 cut-off threshold of 1300 ng/mL. Levels of both adhesins did not correlate with viraemia and were comparable among 1b and non-1b genotypes. Sustained response to interferon was significantly related to low viraemia (P = 0.03), non-lb type (P = 0.04) and low sICAM-1 (P = 0.04), but not to sVCAM-1. On finalizing therapy, patients with normal transaminases had reduced sICAM-1 (P = 0.0005), but not sVCAM-1 levels.


CONCLUSIONS
In chronic hepatitis C, sICAM-1 was a marker of liver necroinflammation while sVCAM-1 reflected fibrosis. Both low sVCAM-1 and pIIIP serum concentrations were strictly linked, suggesting that measuring sVCAM-1 could give information on the degree of liver fibroplasia.
Lo Iacono
O
O
Liver Unit, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
García-Monzón
C
C
Almasio
P
P
García-Buey
L
L
Craxí
A
A
Moreno-Otero
R
R
D000328:Adult; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011347:Procollagen / Q000097:blood; D012372:ROC Curve; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011347:Procollagen; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1