Host genetic determinants in chronic hepatitis C virus infection in Egyptian patients

ABSTRACT

Mechanisms underlying viral persistence and liver damage in chronic HCV are not yet fully clarified, but a complex interplay of virological and immunological factors is implicated. An immunogenetic resistance or susceptibility to chronic hepatitis C virus [HCV] infection may contribute to the course of liver disease and may be linked to the human major histocompatibility complex [MHC]. This study was designed to study the distribution of the HLA class II alleles in patients with chronic hepatitis C and HCV-related cirrhosis to investigate whether these alleles might be associated with protection from or susceptibility to chronic HCV infection. We also aimed to address the correlation of the host HLA class II genotype with the lymphoproliferative response to phytohaemagglutinin [PHA] in vitro. The study included 60 unrelated patients with chronic hepatitis C [15 females, 45 males; mean age, 43 +/- 8.3 years]. A control group of 60 ethnically matched healthy blood donors was also studied [8 females, 52 males; mean age, 25 +/- 4.1 years]. HLA-DRB alleles were studied for patients and controls by a PCR-sequence-specific-primer low-resolution method. HLA-DRB1 03011 and HLA-DRB1 13011 were the most frequently distributed among HCV patients; their percentage of distribution were 26.8% and 28.3% respectively. Conversely, HLA-DRB1 07011 was found at significantly reduced frequency in HCV patients compared to that of the control group. The results also showed that the level of IFN-y was significantly increased in HCV patients [948.5 +/- 135.5] compared to that of the control group [193.6 +/- 21.26]. [t = 30.15, p patients was significantly less than the control group [stimulation index 4.4 +/- 1.03 versus 6.6 +/- 2.5. p liver enzymes, interferon-y and stimulation index. HLA-DRB1 03011 and HLA-DRB1 13011 appear to be associated with HCV infection, while HLA-DRB1 07011 may have a protective feature in chronic HCV infection. These data need further validation and may have major implications and may help to improve our understanding of the immunopathogenesis of chronic HCV infection and elucidate pathways that may serve as different drug targets