Serum Interferon-gamma-inducible protein 10 (CXCL10) is a predictive marker of fibrosis progression after liver transplantation for hepatitis C infection

Abstract

Aims: Recurrence of liver fibrosis after liver transplantation (LT) for hepatitis C infection (HCV) 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 different chemokines including CCL2 and the CXCR3 ligands CXCL9, CXCL10 and CXCL11. We here assessed the predictive value of serum levels of these chemokines with regards to fibrosis recurrence after LT for hepatitis C infection.Material and Methods: We determined in 90 HCV infected organ recipients the serum chemokine levels of CXCL9, CXCL10, CXCL11 and CCL2 by cytometric bead assay six to nine months after LT in a clinically stable situation without acute rejection of the graft, apparent infection or novel co-morbidity and correlated them with histological fibrosis progression in protocol biopsies at years 1, 3, 5 and 7 (median follow-up 3 years). Association of chemokines with fibrosis progression was assessed by univariate and multivariate analyses and Cox regression analysis. Results: Out of the analysed chemokines, CXCL10 levels shortly after LT were strongly associated with early fibrosis regression (years 1 and 3, P=0.005), independent of the known risk factor donor age (P=0.004). Cox regression analysis confirmed the predictive value of CXCL10 with regard to progression to at least F2 or F3 fibrosis during follow-up (P<0.001). A serum level of ≤ 140 pg/ml CXCL10 was significantly predictive of remaining free of F2 fibrosis (P=0.001), while ≤ 220 pg/ml CXCL10 early after LT predicted the absence of F3 fibrosis during follow-up (P=0.035). Conclusion: CXCL10 is a biomarker of fibrosis recurrence after LT for HCV infection. The results might guide patients’ care after transplantation and help to define optimal candidates for antiviral therapy post LT.