Extended human leukocyte antigen haplotype EH18.1 influences progression to hepatocellular carcinoma in patients with hepatitis C virus infection

Our aim was to investigate whether different human leukocyte antigen (HLA) genes might be associated with hepatitis C virus (HCV) infection. DNA obtained from 141 Spanish patients with HCV infection (48 with alanine aminotransferase levels in the range considered to be normal, 47 with liver cirrhosis, and 46 with hepatocellular carcinomas [HCCs]) and from 116 control subjects were typed for HLA-B, HLA-DRB1, and HLA-DQB1 alleles, as well as for major histocompatibility complex class I chain-related gene A (MICA) transmembrane polymorphism. The frequency of HLA-DR11 was increased in HCV carriers, compared with patients with end-stage liver disease (ESLD) (corrected P value [P-c], .0002) and, especially, with patients who P c had HCC (P-c = .003). The frequency of the HLA-B18 allele was increased in patients with HCC, and the allele was absent in HCV carriers (P-c = .003). The MICA-A4 allele was overrepresented in patients with HCC, compared with HCV carriers (P-c = .0002). The DR3/MICA-A4/B18 haplotype was associated with HCC (P-c = .01). In conclusion, HLA-DR11 seems to be protective against the development of severe forms of infection, and the DR3/MICA-A4/B18 haplotype may be an important factor in the progression to the most severe HCV-infection status.