Association between quasispecies variants of hepatitisBvirus, as detected by high‑throughput sequencing, and progression of advanced liver disease in Indonesian patients.

Abstract

Mutations in the hepatitisB virus (HBV) Xregion and truncation of the preS2region are well‑known to affect the progression of liver disease. Recently, it has been observed that an increasing number of Sregion quasispecies variants are associated with disease progression. However, few studies have analysed quasispecies of the whole genome using high‑throughput sequencing methods. Using high‑throughput sequencing, whole‑genome variations in 12Indonesian patients infected with HBV (eight with advanced liver disease and four with chronic hepatitis) were examined. Variations with cut‑off values of ≥1% of the total viral population were investigated. It was revealed that within the four open reading frames, quasispecies variations of the SandXregions were higher in advanced liver diseases compared with in chronic hepatitis (Sregion: 89.53vs.50.69%, P=0.047; Xregion: 76.95vs.35.88%, P=0.044). Notably, the mutation frequencies in the basal core promoter, Bcell epitope, RTBoxG, RNAseH and smallSregion were greater in advanced liver disease. The proportion of quasispecies variants increased for the majority of the mutations, with the exception for W196* in the smallSgene, during disease progression. The present study demonstrated that quasispecies in the SandXregions of the HBV genome changed during disease progression and were associated with advanced liver disease development in Indonesian patients with HBV.