Comparison of pre-S1/S2 variations of hepatitis B virus between asymptomatic carriers and cirrhotic/hepatocellular carcinoma-affected individuals

Aim of the study
Host and viral factors can influence the clinical course of chronic hepatitis B virus (HBV) infection. Mutations in pre-S1/S2 gene regions are among the most important viral factors determining the HBV infection outcome. The aim of this study was to investigate the role of pre-S1/S2 mutations in HBV infection outcome.

Material and methods
A total of 52 samples from 26 asymptomatic carriers (ASCs) and 26 liver cirrhosis/hepatocellular carcinoma (LC/HCC) patients were enrolled. The HBV DNA genome was extracted from the sera, and pre-S1/S2 regions of the samples were amplified by nested-polymerase chain reaction, prior to being subjected to sequencing, sequence investigation and phylogenetic analysis.

Results
Certain deletions were detected mostly located at the boundary of the pre-S1 and pre-S2 regions. These deletions were detected more frequently in ASC cases than in LC/HCC patients (p < 0.007). The rate of critical point mutations, including L11Q, N37S and K38R, was significantly higher in the ASC group, whereas the A49V substitution rate was significantly higher in the LC/HCC group (p < 0.05). The phylogenetic analysis indicated that all the sequences belonged to genotype D.

Conclusions
According to the results, point mutations such as L11Q, N37S, K38R and A49V, as well as certain deletions, may be associated with HBV infection outcome, among an HBV genotype D pure population.