Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection

Abstract

The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8 þ and CD4 þ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30-80%) and lower response rates have been reported among African Americans (AA; B30%) compared to Caucasian Americans (CA; B50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were associated with response to therapy and racial differences in AA and CA sustained virologic response (SVR) rates. We genotyped alleles at 8 MHC loci: 3 class I (A, B and C) and 5 class II (DRB1, DQA1, DQB1, DPA1 and DPB1) loci in 373 individuals (179 AA and 194 CA) with genotype-1 HCV infections, who were treated with peginterferon-a-2a and ribavirin. We observed carriage of A*02 (RR ¼ 1.33(1.08-1.64); P ¼ 0.008), B *58 (RR ¼ 1.84(1.24-2.73); P ¼ 0.002) and DPB1*1701 (RR ¼ 1.57(1.09-2.26); P ¼ 0.015) to be associated with SVR after adjustment for other predictors of response. In analysis of AA and CA subgroups separately, we observed potential, though not statistically significant, differences in these MHC associations. Variation in the immunogenetic background of HCV-infected individuals might account for some observed variation in viral-specific immunity and courses of disease. In this regard, future studies examining broader patient populations are warranted.

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin

“…In this regard, it is well known that MHC genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8 + and CD4 + T cells (18,34) . Previous studies have shown an impact of MHC gene variants and response to therapy in chronic HCV infection (17,28,31,36) . Our finding contradicts the previously described association between H63D mutation and higher SVR (6) .…”

“…Elevated serum ferritin has long been recognized as a marker of poor response to antiviral treatment in chronic HCV infected patients (3,12,16) , however the mechanism underlying this effect is not clear and the role of HFE polymorphisms has not yet been established. Interestingly, there is intriguing evidence of an association between HFE polymorphism and higher SVR rates (8,31) , but this issue has not been specifically investigated among HCV patients with high serum ferritin, which are recognized as having difficult to treat disease.…”

Does a relationship of HLA B alleles with course of hepatitis C virus infection in children and youth and efficacy of its treatment exist?

“…cechy genetyczne pacjenta, szczególnie układ genów dla antygenów zgodności tkankowej -główny układ zgodności tkankowej (major histocompatibility complex -MHC), ludzkie antygeny leukocytarne (human leucocyte antigens -HLA) [1][2][3][4][5][6][7]. Skuteczność podejmowanej terapii także być może ma związek z układem genów dla HLA [8][9][10].…”

“…W wielu badaniach brano pod uwagę antygeny zgodności tkankowej klasy I [1,8,[11][12][13] i II [1,14] jako mające wpływ na podatność na zakażenie [1,11,13], prawdopodobieństwo jego przejścia w stan przewlekły [2-4, 7, 14, 15], progresję i dynamikę uszkodzenia wątroby [5,6,12,13], występowanie powikłań pozawą-trobowych [16], a także skuteczność terapii [8][9][10]17]. Takie związki potwierdzono w wielu badaniach [1-11, 13-15, 17].…”

“…stwierdzili jednak związek HLA z odpowiedzią na leczenie (terapia skojarzona pegylowanym interferonem α i rybawiryną, pacjenci zakażeni genotypem 1 wirusa) w zakresie HLA B: allel HLA B*58 wystę-pował częściej u pacjentów, którzy uzyskali trwałą odpowiedź wirusologiczną [10]. Tymczasem Tseng i wsp., analizując wyniki leczenia w grupie ponad 100 pacjentów, odnotowali, że z niekorzystnym rokowaniem wiąże się obecność antygenu HLA B60 [9].…”