The recurrence of liver fibrosis after liver transplantation (LT) for hepatitis C virus (HCV) infection is responsible for graft loss and patient mortality. Although the contribution of the immune system to fibrosis recurrence is anticipated, systematic studies evaluating immune parameters as predictive markers of allograft fibrosis are lacking. The infiltration of immune cells into the graft is governed by chemokines. Here we assessed the predictive value of serum levels of chemokines [chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, CXCL11, and chemokine (C-C motif) ligand 2 (CCL2)] with respect to fibrosis recurrence after LT in 90 HCV-infected organ recipients. Chemokines were determined within the first and third years after LT and were correlated with histological fibrosis progression in protocol biopsy samples at 1, 3, 5, and 7 years (median follow-up = 3 years). The association of chemokines with fibrosis progression was assessed by univariate and multivariate analyses and by Cox regression analysis. The results for the analyzed chemokines showed that CXCL10 levels in the first year after LT were strongly associated with early fibrosis recurrence (P = 0.005) independently of risk confounders (including the donor age, HCV viral load, HCV genotype, acute rejection, and inflammatory activity). As assessed by Cox regression analysis, a CXCL10 serum level ≤ 140 pg/mL was significantly predictive of the absence of F2 fibrosis (P = 0.001), whereas a level ≤ 220 pg/mL early after LT predicted the absence of F3 fibrosis during follow-up (P = 0.035).
Conclusion: CXCL10 is an independent biomarker of the recurrence of significant fibrosis after LT for HCV infection. These results might guide patients' care after transplantation and help us to select optimal candidates for antiviral therapy post-LT.
Copyright © 2010 American Association for the Study of Liver Diseases.