HLA-DRB1 donor-recipient mismatch affects the outcome of hepatitis C disease recurrence after liver transplantation.
OBJECTIVE
This study extends our previously reported observations that various immunological factors are associated with the occurrence of histologically proven recurrent hepatitis C. The two specific issues investigated were to confirm the associations of MHC alleles and donor/recipient mismatch with the occurrence of recurrent hepatitis C in an independent cohort of newly transplanted patients and to look for immunologic and nonimmunologic variables affecting the severity of the recurrent disease.


METHODS
Two separate cohorts of consecutive patients were studied: a look-back cohort (LC) of 120 patients and a cohort for studying the disease progression (CSDP) of 190 patients. Protocol liver biopsies were obtained at least 1, 3, 5, 7, and 10 years after liver transplantation (LT).


RESULTS
A fully mismatched donor/recipient pair at the DRB1 locus was confirmed to be associated with both the recurrence of histologic hepatitis in the LC (59% vs 23%, P = .0002) and its progression beyond stage 3 in the CSPD (71.4% vs 39.3%, P = .0003). Relevant immunologic and nonimmunologic variables were included into a multivariate Cox proportional model and three variables, namely, donor age, full HLA-DRB1 donor-recipient mismatch, and HLA B14, resulted in independent risk factors for the development of severe fibrosis.


CONCLUSIONS
This study provides evidence that DRB1 donor-recipient mismatch affects both the occurrence and progression of recurrent hepatitis C disease. This information is clinically relevant as it may help to better allocate organs and to recognize patients at risk for progression so that specific interventions can be implemented.
Belli
Luca Saverio
LS
Department of Gastroenterology and Hepatology, "Crespi" Ospedale Niguarda, Milan, Italy. epatogastro@ospedaleniguarda.it
Burra
Patrizia
P
Poli
Francesca
F
Battista Alberti
Alberto
A
Silini
Enrico
E
Zavaglia
Claudio
C
Fagiuoli
Stefano
S
Prando
Daniela
D
Espadas de Arias
Alejandro
A
Boninsegna
Sara
S
Tinelli
Carmine
C
Scalamogna
Mario
M
de Carlis
Luciano
L
Pinzello
Giovambattista
G
D000328:Adult; D000368:Aged; D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006526:Hepatitis C / Q000209:etiology*; D006650:Histocompatibility Testing; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012008:Recurrence
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains