Influence of immunogenetic background on the outcome of recurrent hepatitis C after liver transplantation

In immunocompetent patients, specific human leukocyte antigen (HLA) class I I alleles have been associated with the severity of hepatitis C virus (HCV) -related disease, in particular, HLA-DRB1*11 has been found to exert a prot ective effect. The authors have analyzed the role of HLA class I and II all eles in determining the frequency, timing, and progression of histologicall y proven recurrent hepatitis C in 89 patients who underwent a liver transpl ant for HCV-related cirrhosis. In addition, the influence of HLA mismatch b etween donor and recipient, HCV genotype, and use of steroid pulses was als o evaluated. Median patient follow up was 35 months (range 4-119). HLA-DRB1 typing was performed by genomic analysis in all cases. Liver biopsies were obtained routinely and at least at yearly intervals. Histologically proven recurrent hepatitis was observed in 46 patients (52%), 10 patients progres sing to stage 5-6 fibrosis in most cases within 2 years after transplant. B y univariate analysis, 3 variables, HLA-B14, HLA-DRB1*04, and HLA-DRB1 dono r/recipient mismatch, showed a significant effect on time to recurrent hepa titis C disease. These parameters were included in a multivariate regressio n model along with HCV genotype, treatment with steroid pulses and DRB1*11. HLA-B14, HLA-DRB1*04, and HLA-DRB1 donor/recipient mismatch were confirmed to provide a significant and independent contribution to the risk of hepat itic disease recurrence. As for the severity of the disease, none of the 10 patients with stage 5-6 hepatitis carried the HLA-DRB1*11 allele, in line with what was observed in nontransplant subjects. Our results suggest that in posttransplant recurrent hepatitis C, immunogenetic factors are relevant in determining HCV infection outcome.