Mannose binding lectin (MBL) is a pattern-recognition molecule of the innate immune system. The roles of MBL and its gene (mbl2) polymorphisms, -221X/Y and
codon 54A/B, in hepatitis B virus (HBV)
infection were investigated in this study. We recruited 320 nonprogressed
hepatitis B surface antigen (
HBsAg) carriers; 199 progressed
HBsAg carriers with
hepatocellular carcinoma or
cirrhosis; 87 spontaneously recovered individuals who were
HBsAg negative and anti-HBs and anti HBc positive; and 484 controls who were naïve to HBV. There was no significant difference between nonprogressed carriers, spontaneously recovered individuals, and controls in terms of serum MBL levels and mbl2 polymorphisms distributions. However, the low MBL genotypes had a dose-dependent correlation with the
cirrhosis and
hepatocellular carcinoma in progressed carriers with odds ratios of 1.36 and 3.21 for the low and extremely low MBL genotypes, respectively (P = .01). The low-expression promoter haplotype XA (OR = 1.97) and the mutant haplotype YB (OR = 1.90) were also associated with the
cirrhosis and
hepatocellular carcinoma (P = .002). As expected, the lower serum MBL levels in progressed carriers as compared with nonprogressed carriers were due to an overrepresentation of low and extremely low MBL genotypes. Moreover, MBL could bind
HBsAg in a dose- and
calcium-dependent and
mannan-inhibitable manner in vitro, suggesting that binding occurs via the
carbohydrate recognition domains. This binding also enhanced C4 deposition. In conclusion, these results suggest that low MBL genotypes associate with the occurrence of
cirrhosis and
hepatocellular carcinoma in progressed
HBsAg carriers, and MBL can bind
HBsAg.