Association between HLA class II genotype and spontaneous clearance of hepatitis C viraemia.

Hepatitis C virus (HCV) infection becomes chronic in most cases, with only 10-20% of those infected not developing persistent viraemia. The immune response to HCV may be an important determinant of disease resolution and can be influenced by a number of host factors. The aim of this study was to assess the role of host HLA class II type in influencing viral clearance or susceptibility to chronic HCV infection. We have compared the distribution of HLA DRB1, DQA1 and DQB1 alleles in 49 patients with spontaneous clearance of HCV infection (HCV antibody positive but persistently HCV RNA negative), with 55 chronically infected patients and 134 racially matched controls. Three alleles were found significantly more frequently in patients with spontaneous viral clearance compared to those with chronic infection-DRB1*04 (pc=0.0022, odds ratio OR=4.52), DQA1*03 (pc=0.0012, OR=4.69) and DQB1*0301 (pc=0.0078, OR=5.09). DQB1*0302 was found at reduced frequency in all HCV-antibody-positive patients compared to controls (pc=0.0063). DRB1*04, DQA1*03 and DQB1*0301 are associated with spontaneous clearance of HCV viraemia, with the primary association likely to be with DQB1*0301 and the associations with DRB1*04 and DQA1*03 being due to linkage. In addition, DQB1*0302 is associated with protection from HCV infection. These findings suggest that host HLA class II genotype is an important factor in determining the outcome of infection with hepatitis C virus.