Donor‐recipient sharing of HLA class II alleles predicts earlier recurrence and accelerated progression of hepatitis C following liver transplantation

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Abstract
Both direct viral cytopathic effects and host immune responses appear to be important in the pathogenesis of hepatitis C virus (HCV) infection. Liver transplantation provides a means to explore the role of the immune system in the development of HCV‐related liver damage through comparing the natural history of HCV in patients with different degrees of donor‐recipient human leukocyte antigen (HLA) matching. We evaluated 36 patients with recurrent hepatitis C viremia following liver transplantation to determine whether hepatocellular injury or progression to bridging fibrosis occur more rapidly when donor and recipients share HLA alleles. HLA typing for the HLA‐A and HLA‐B loci was performed by serological techniques and PCR‐based oligotyping was used to type alleles of the DRB1, DRB3, DQA1, and DQB1 loci. A median of eight liver biopsies, obtained during a median follow‐up of 36 months, were reviewed per patient. Donor‐recipient sharing of alleles of HLA‐DQB1 or DRB1 was associated with more rapid development of recurrent hepatitis by univariate analysis (χ2=5.7,P=0.02 and χ2=5.54,P=0.02 respectively). However, only sharing of HLA‐DRB1 alleles was identified as an independent predictor of reduced time to recurrent histologic injury by multivariate analysis (χ2=5.74,P= 0.02). Furthermore, sharing of HLA‐DRB3 and histologic evidence of rejection were associated with more rapid progression to bridging fibrosis both by univariate methods (χ2=4.12,P=0.04 and χ2=4.66,P=0.03 respectively), and by multivariate analysis (χ2= 13.01,P=0.001). These findings suggest that HLA class II‐restricted immune responses may contribute to the pathogenesis of HCV‐related liver injury in liver transplant recipients.

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