Association between quasispecies variants of hepatitis B virus, as detected by high­throughput sequencing, and progression of advanced liver disease in Indonesian patients.

ABSTRACT

Mutations in the hepatitis B virus (HBV) X region and truncation of the preS2 region are well­known to affect the progression of liver disease. Recently, it has been observed that an increasing number of S region quasispecies variants are associated with disease progression. However, few studies have analysed quasispecies of the whole genome using high­throughput sequencing methods. Using high­throughput sequencing, whole­genome variations in 12 Indonesian patients infected with HBV (eight with advanced liver disease and four with chronic hepatitis) were examined. Variations with cut­off values of ≥1% of the total viral population were investigated. It was revealed that within the four open reading frames, quasispecies variations of the S and X regions were higher in advanced liver diseases compared with in chronic hepatitis (S region 89.53 vs. 50.69%, P=0.047; X region 76.95 vs. 35.88%, P=0.044). Notably, the mutation frequencies in the basal core promoter, B cell epitope, RT Box G, RNAseH and small S region 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 small S gene, during disease progression. The present study demonstrated that quasispecies in the S and X regions of the HBV genome changed during disease progression and were associated with advanced liver disease development in Indonesian patients with HBV.