Title | Donor-recipient sharing of HLA class II alleles predicts earlier recurrence and accelerated progression of hepatitis C following liver transplantation |
Publication Type | Journal Article |
Year of Publication | 1998 |
Authors | Cotler SJ, Gaur LK, Gretch DR, Wile M, Strong DM, Bronner MP, L., Carithers R. J, Emond MJ, Perkins JD, Nelson KA |
Journal | Tissue Antigens |
Volume | 52 |
Issue | 5 |
Pagination | 435 - 43 |
Date Published | Nov |
ISSN | 0001-2815 (Print) 0001-2815 (Linking) |
Accession Number | 9864033 |
Keywords | *Alleles, Adult, Disease Progression, Female, Hepatitis C, Chronic / genetics / *immunology, Histocompatibility, Histocompatibility Antigens Class II / *genetics / *immunology, Humans, Liver Transplantation / adverse effects / *immunology, Male, Middle Aged, Recurrence, RNA, Viral / blood, Time Factors |
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 (chi2=5.7, P=0.02 and chi2=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 (chi2 =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 (chi2=4.12, P=0.04 and chi2=4.66, P=0.03 respectively), and by multivariate analysis (chi2=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. |
Notify Library Reference ID | 378 |