Influence of HLA haplotypes on the clinical courses of individuals infected with hepatitis C virus.

The human leukocyte antigen is a crucial genetic factor that initiates or regulates immune response by presenting foreign or self antigens to T lymphocytes. The aim of this study was to investigate whether HLA polymorphism is associated with the onset or progression of liver injury in chronic hepatitis C virus (HCV) infection. We determined HLA class I antigens and class II alleles in 130 hepatitis C virus (HCV)-infected patients (33 carriers with persistently normal alanine transaminase [ALT] values and 97 patients with chronic liver disease [CLD]). HLA class I (A, B) was typed serologically, and class II (DRB1, DQB1) was typed by means of polymerase chain reaction-restriction fragment length polymorphism methods. The frequencies of DRB10405 and DQB10401 were higher in HCV-infected patients than in uninfected subjects. Among HCV-infected patients, the frequencies of B54, DRB10405, and DQB10401 were significantly higher in patients with CLD than in those carriers with persistently normal ALT values, whereas DRB11302, DRB11101, and DQB10604 were more frequently found in carriers with persistently normal ALT values than in patients with CLD. From extended haplotype analyses, in carriers with B54-DRB10405-DQB10401 haplotype, the risk of having liver injury was 13.2 times greater than in carriers with DRB10405-DQB10401 but without B54 [P = 0.0015, Haldane odds ratio = 13.2 (95% confidence interval, 1.7-103.8)]. In contrast, carriers with B44-DRB11302-DQB10604 had a 12.7-fold lower relative risk of developing liver injury compared to those with the haplotype containing B44 but not DRB11302-DQB10604 [P = 0.0076, Haldane odds ratio = 0.079 (0.009-0.695)]. Our findings show that extended haplotypes including class I B54 are closely associated with the progression of liver injury, whereas extended haplotypes including class II DRB11302-DQB1*0604 are associated with low hepatitis activity in chronic HCV infection.