Hepatitis B virus‐induced hepatocellular carcinoma: functional roles of MICA variants

Summary Hepatitis B virus infection is a high‐risk factor for hepatocellular carcinoma. The human major histocompatibility complex class I chain‐related gene A ( MICA ) is a ligand of the NKG2D receptor that modulates the NK and T ‐cell‐mediated immune responses and is associated with several diseases. This study determined the effects of MICA polymorphisms during HBV infection and HBV ‐induced HCC . We conducted a case–controlled study in a Vietnamese cohort and genotyped ten functional MICA polymorphisms including the microsatellite motif in 552 clinically classified hepatitis B virus patients and 418 healthy controls. The serum soluble MICA levels ( sMICA ) were correlated with MICA variants and liver enzyme levels. We demonstrated a significant contribution of MICA rs2596542G/A promoter variant and nonsynonymous substitutions MICA‐129Met/Val , MICA‐251Gln/Arg, MICA‐175Gly/Ser , triplet repeat polymorphism and respective haplotypes with HBV ‐induced HCC and HBV persistence. The circulating sMICA levels in HBV patient groups were elevated significantly compared with healthy controls. A significant contribution of studied MICA variants to sMICA levels was also observed. The liver enzymes alanine amino transferase ( ALT ), aspartate transaminase ( AST ), total bilirubin and direct bilirubin were positively correlated with sMICA levels suggesting sMICA as a biomarker for liver injury. We conclude that MICA polymorphisms play a crucial role in modulating innate immune responses, tumour surveillance and regulate disease susceptibility during HBV infection.