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

Putri,Wahyu  Aristyaning; Yano,Yoshihiko; Yamani,Laura  Navika; Liang,Yujiao; Mardian,Yan; Utsumi,Takako; Soetjipto,Soetjipto; Lusida,Maria  Inge; Hayashi,Yoshitake

doi:10.3892/mmr.2019.10250

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

Authors:
- Wahyu Aristyaning Putri
- Yoshihiko Yano
- Laura Navika Yamani
- Yujiao Liang
- Yan Mardian
- Takako Utsumi
- Soetjipto Soetjipto
- Maria Inge Lusida
- Yoshitake Hayashi
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Affiliations: Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan, Indonesia‑Japan Collaborative Research Centre for Emerging and Re‑emerging Infectious Disease, Institute of Tropical Disease, Airlangga University, Surabaya, East Java 60115, Indonesia, Division of Molecular Medicine and Medical Genetics, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
Published online on: May 16, 2019 https://doi.org/10.3892/mmr.2019.10250
Pages: 16-24

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Abstract

Mutations in the hepatitis B virus (HBV) X region and truncation of the preS2 region are well‑known 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 high‑throughput sequencing methods. Using high‑throughput sequencing, whole‑genome variations in 12 Indonesian 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 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.

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