Elevated Plasma CXCL8 Concentrations in Significant Fibrosis but Not in Subclinical Rejection After Adult Liver Transplantation

Abstract

Background. The noninvasive detection of subclinical graft injury including subclinical T cell–mediated rejection (subTCMR) is one of the unresolved challenges after liver transplantation. Recently, serum C-X-C motif chemokine ligand 8 (CXCL8) was proposed as a highly accurate marker of subTCMR in pediatric liver transplant recipients. We aimed to evaluate the accuracy of the quantification of this chemokine for predicting subTCMR in adult liver transplant recipients, as well as its capacity to classify patients who could benefit from immunosuppression reduction. Methods. Plasma CXCL8 concentrations were measured retrospectively in a prospectively collected cohort of adult liver transplant recipients with well-characterized histologic phenotypes. Results. In total, 78 patients were included. Median plasma CXCL8 concentrations did not differ (P = 0.24) between patients without histological evidence of rejection (3.6 [0.4–22.0] pg/mL), subTCMR (11.5 [0.4–41.0] pg/mL), clinical TCMR (9.4 [0.4–40.5] pg/mL), and other etiologies of graft injury (8.7 [0.4–31.2] pg/mL). Likewise, plasma CXCL8 concentrations did not discriminate between patients within and outside histologic criteria for immunosuppression reduction that were proposed by the 2016 Banff Working Group on Liver Allograft Pathology (cutoff: 10.9 pg/mL, sensitivity: 0.48, and specificity: 0.79). Furthermore, weak correlation was found between plasma CXCL8 and alanine aminotransferase and aspartate aminotransferase (Spearman ρ = 0.18 and 0.25). Patients with significant fibrosis (17.8 [0.4–40.5] pg/mL) showed higher plasma CXCL8 concentrations than patients without fibrosis (8.2 [0.4–41.0] pg/mL; P = 0.05). Conclusions. Plasma CXCL8 concentrations are not predictive of subclinical graft injury or of histological criteria for the minimization of immunosuppression in adult liver transplant recipients.