Sequence analysis of the Pre-S gene in chronic asymptomatic HBV carriers with low-level HBsAg

In a hepatitis B virus (HBV)-infected population, persistently low expression levels of serum HBV serum antigen (HBsAg) are present, particularly in chronic asymptomatic HBV carriers (ASCs). The present study sequenced the HBV Pre-S gene, and aimed to elucidate its features in ASCs with low HBsAg expression compared with in the established HBV Pre-S reference gene sequences from ASCs with high HBsAg expression. A total of 1,308 ASCs were grouped according to HBsAg serum levels (cut-off value, 10 IU/ml), and clinical characteristics were analyzed in detail. The HBV Pre-S gene was sequenced in 276 ASCs with low-level HBsAg; in addition, 100 of the remaining 1,032 ASCs with high-level HBsAg were randomly selected for HBV Pre-S gene sequencing on the basis of age matching with the low-level HBsAg group. Comparative analysis of the gene sequences from these groups was subsequently conducted. The major clinical features of the population with low-level HBsAg were as follows: Most were ASCs with chronic HBV infection; 97.1% were HBsAg/anti-HBe/anti-HBc-positive; 82.54% carried the B genotype; and 84.13% displayed the adw serotype. The results indicated that there were novel and meaningful mutations, including co-mutations, at numerous loci and sites in the Pre-S gene, as well as deletion mutations in the Pre-S2 gene. These mutations in the Pre-S1 and Pre-S2 gene frag ments accounted for 65.38% (68/104) of the 104 B genotype cases in the low-level HBsAg group and 90.91% (20/22) of the 22 C genotype cases in the low-level HBsAg group, respectively. In conclusion, Pre-S gene mutations may be associated with HBV replication defects, which may be the cause of the observed low expression levels of HBsAg.