D. W. Forner1, R. G. Sperry2, R. S. Liwski2,3, I. P. Alwayn1,2,3 1Dalhousie University,Department Of Surgery,Halifax, Nova Scotia, Canada 2Dalhousie University,Department Of Pathology,Halifax, Nova Scotia, Canada 3Dalhousie University,Department Of Microbiology & Immunology,Halifax, Nova Scotia, Canada
Introduction:
For many forms of end-stage liver disease, transplantation is the only available therapy. While current outcomes represent a vast improvement over initial liver transplants, there is room for improvement; rates of acute rejection remain around 20%, with rates of chronic rejection only slightly lower. In particular, the usefulness of donor specific HLA antibody (DSA) as a predictor of liver rejection is controversial. Therefore, this study aimed to evaluate the utility of both standard single antigen bead (SAB) assay and a modified C1q assay in the prediction of liver transplant outcomes.
Methods:
This study is a retrospective chart review of liver transplant patients coupled with assaying of patient sera by both standard SAB assay and modified C1q assay. Patient records were reviewed from January 1st 2009 to December 31st 2013.
Results:
In total, 100 patients whom underwent liver transplant met inclusion criteria and had pre-transplant sera tested for DSAs by SAB assay. Twenty-eight patients with confirmed or suspected DSA by SAB assay underwent screening by modified C1q assay.
Twenty-two patients experienced biopsy proven acute cellular rejection (ACR). One patient experienced biopsy confirmed chronic rejection (CR; 1%). An additional 13 individuals experienced suspected rejection (13%).
Twenty-five patients were DSA positive by SAB assay (DSASAB; 25%). These patients were more likely to experience ACR than those with no DSASAB (36% vs 17%, p < 0.05). The positive predictive value was found to be 41%, while the negative predictive value was found to be 80%.
Examination by the modified C1q assay found thirteen patients possessed complement-activating DSAs (DSAC1q; 13%). Patients with DSAC1q were not more likely to experience ACR than those without (8% vs 24%, p > 0.05).
Conclusion:
Patients with DSA detected using standard SAB assay were more likely to experience ACR. However, the predictive value of this assay was not found to be particularly useful, with nearly two thirds of patients possessing DSASAB experiencing no rejection. Despite the hypothesized advantage the C1q assay holds in the prediction of rejection, patients with complement-fixing DSA were not more likely to experience rejection. This finding is in agreement with recent study by Kubal et al. (2013) examining the clinical utility of the C1q assay. In conclusion, this study offers further evidence that DSA may play a role in liver transplantation outcomes, and larger studies should be carried out to assess the role of complement-fixing antibodies in liver transplantation.