HLA-DQA1 & DQB1 variants associated with hepatitis B virus-related chronic hepatitis, cirrhosis & hepatocellular carcinoma.

BACKGROUND & OBJECTIVES: Clinical outcome after hepatitis B virus (HBV) exposure varies extremely from spontaneous clearance to chronic hepatitis B and often progresses to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Host genetic factor plays an important role in the regulation of immune response. This study was aimed to investigate whether HLA class II DQA1 and DQB1 gene polymorphism were associated with chronic hepatitis B infection and in the development of HBV-related LC and HCC.

METHODS

DQA1 and DQB1 allele polymorphism were studied in 187 patients with HBV-related liver diseases (which included 73 chronic hepatitis B, 84 LC and 30 HCC patients) and 109 controls who had spontaneously recovered from HBV infection using polymerase chain reaction amplification with sequence-specific primers.

RESULTS

Our data suggested that DQA10101/2/4 [odds ratio (OR)=2.78; P=0.003], DQA10103 (OR=2.64; P=0.0007) and DQB10302/3 (OR=2.15; P=0.01) were associated with the protection from chronic HBV infection, whereas DQB10402 (OR=0.25; P=0.001) showed susceptible effect on chronic HBV infection. DQB10601 (OR=3.73; P=0.006) conferred protective effect from developing LC; similarly, DQB10302/3 (OR=5.53; P=0.05) and DQB10402 (OR=0.00; P=0.001) conferred protective effect from developing HCC. However, DQA10601 and DQB1*0503 showed susceptible effect on chronic HBV infection; these associations were no longer significant after Bonferroni correction.

INTERPRETATION & CONCLUSIONS: Our results revealed HLA-DQA10101/2/4 - DQA10103 - DQB10302/3 and DQB10601 as protective and DQB1*0402 as risk alleles. The study suggests that various subtypes of HLA-DQA1 and DQB1 are associated with both HBV clearance and development of chronic HBV infections.