DONOR-RECIPIENT SHARING OF HLA CLASS II ALLELES PREDICTS EARLIER RECURRENCE OF HCV FOLLOWING LIVER TRANSPLANTATION.

1.8
#51
DONOR-RECIPIENT SHARING OF HLA CLASS II ALLELES PREDICTS EARLIER RECURRENCE OF HCV FOLLOWING LIVER TRANSPLANTATION.
J.-Q. He , K. Nelson , R.L. Carithers, Jr. , A.M. Larson , J.D. Parkins and Lakshmi K. Gaur . Vancouver BC, Canada, University British Columbia McDonald Research Labs ; Puget Sound Blood Center ; University of Washington and Seattle WA, USA, Unversity of Washington, Wa Natl Primate Res Ctr .

We previously reported that recurrence of HCV in a transplanted liver was accelerated if donor and recipient share certain HLA class II alleles. Here we extend our study to a larger group of 120 Caucasian recipients with HCV infection who received liver transplantation with minimum one month follow up. An average of 6.4 allograft biopsies was performed per patient. HLA typing for the DRB1, DQA1 and DQB1 loci was performed by PCR-based oligotyping. HCV disease of the graft was defined by liver biopsy. The Kaplan-Meier product-limit estimate was used for univariate analysis of time-dependent events with comparison between groups performed via the Peto-Wilcoxon test. The Cox proportional hazard was used for multivariate analysis for time-dependent events. Results: Eighty-one out of 120 recipients (67.5%) developed HCV disease during a median of 23 months follow up period. Donor-recipient sharing of alleles of HLA-DRB1 or DQB1 was associated with more rapid development of recurrent hepatitis both by univariate analysis (chi²=11.8, p=0.0006 and chi²=7.2, p=0.007, respectively) and by multivariate analysis (chi²=4.47, p=0.03 and chi²=7.6, p=0.006, respectively). We also confirmed that histological evidence of rejection was associated with rapid development of recurrent hepatitis both by univariate and multivariate methods (chi²=8.3, p=0.004 and chi²=9.7, p=0.002, respectively). However, the DQA1 allele sharing did not impact the time frame of HCV recurrence in our dataset. In conclusion we confirm our previous finding that HLA class II-restricted immune responses contribute to the pathogenesis of HCV-related liver injury in a large set of Caucasian recipients.