Donor-specific hyporesponsiveness in ELISPOT assay is associated with early recurrence of hepatitis C in liver transplant recipients

Abstract

Recurrence of hepatitis C in liver transplant recipients is a common event that often leads to loss of the allograft. There are no means to prevent, or even predict, those patients who are more prone to early aggressive recurrence. Therefore there is an increased need for tailored immunosuppression protocols specific to this patient population. Fifteen liver transplant recipients (eight hepatitis C virus [HCV]+; 7 HCV-) were followed for 12-24 months after transplantation. The frequency of donor-specific interferon (IFN)-gamma- or interleukin-10-producing lymphocytes was monitored using ELISPOT assays. Of the eight HCV+ recipients, six experienced recurrence within the first year after transplant. All six patients had very low (negligible) frequency of donor-specific IFN-gamma precursors; in most cases not higher than the nonstimulated (spontaneous) secretion rate. The other two patients who did not recur exhibited donor-specific IFN-gamma reactivity. A significant difference in the frequency of alloantigen-specific T cells was observed between HCV+ recipients and patients with other indications for transplantation. The results of this preliminary study suggest that posttransplant monitoring of the frequency of donor-specific IFN-gamma-producing precursors may differentiate a subset of patients at risk for early recurrent hepatitis C and therefore may help to devise treatment strategies for HCV+ liver recipient after transplantation.