Donor-recipient sharing of HLA class II alleles predicts earlier recurrence and accelerated progression of hepatitis C following liver transplantation.
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.
Cotler
S J
SJ
Department of Medicine, University of Washington Medical Center, Seattle, USA.
Gaur
L K
LK
Gretch
D R
DR
Wile
M
M
Strong
D M
DM
Bronner
M P
MP
Carithers
R L
RL
Emond
M J
MJ
Perkins
J D
JD
Nelson
K A
KA
D000328:Adult; D000483:Alleles; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology*; D006648:Histocompatibility; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D013997:Time Factors
D000949:Histocompatibility Antigens Class II; D012367:RNA, Viral