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 fragments 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.