Skip to content
DraconiticResearch
Search Sources API
190,839 studies31 sourcesUpdated 3 min ago
Peer-reviewedCC BY 4.0PLOS One

Hepatitis B virus genome mutations in precore and basal core promoter regions among HBeAg-negative chronic hepatitis B patients with high viral load in Indonesia

  • Dewi Wulandari1
  • Yan Mardian2
  • Sunita3
  • Kadek Aditya Darmayoga4
  • Rindha Agustiani5
  • Khoirunnisa
  • Youdiil Ophinni
5 affiliations
  1. 1Department of Clinical Pathology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
  2. 2The Hakubi Center for Advanced Research, Kyoto University, Kyoto, Japan
  3. 3Center for Southeast Asian Studies (CSEAS), Kyoto University, Kyoto, Japan
  4. 4Department of Host Defense, Immunology Frontier Research Center (IFReC), Osaka University, Osaka, Japan
  5. 5Division of Clinical Virology, Center for Infectious Diseases, Kobe University, Kobe, Japan
Open at sourcePDFDOICite

Abstract

Hepatitis B e antigen (HBeAg) is widely used as a marker for active HBV replication and serves as a surrogate for HBV DNA > 200,000 IU/mL to determine eligibility for tenofovir disoproxil fumarate (TDF) prophylaxis to prevent vertical transmission, according to WHO guidelines. However, some HBeAg-negative patients still harbor high viral loads. Mutations in the precore (PC) and basal core promoter (BCP) regions may reduce or abolish HBeAg expression without necessarily suppressing viral replication. Next-generation sequencing (NGS)-based characterization of these mutations remains limited in Indonesia. This study aimed to analyze the mutation prevalence in the BCP and PC regions associated with HBeAg negativity in Indonesian patients. We conducted a cross-sectional study of 32 chronic HBV treatment-naïve, unvaccinated patients with HBV DNA > 200,000 IU/mL (16 HBeAg-negative, 16 HBeAg-positive) at Cipto Mangunkusumo General Hospital. BCP and PC mutations were analyzed using NGS, classifying mutations as major (mutation frequency index [MFI] ≥20%) or minor (MFI 1– < 20%). Associations were analyzed using the Chi-square or Fisher’s exact test and p-values were adjusted using the Benjamini-Hochberg procedure. Among 29 major mutation sites, PC mutations A1846T/C and G1896A were more frequent in HBeAg-negative than HBeAg-positive patients (81.3% vs 6.3% and 75.0% vs 12.5%, respectively; all adjusted p = 0.019). Combined analysis showed higher mutation frequencies in HBeAg-negative patients (93.8%, 81.3%, and 62.5% for A1846T/C, G1896A, and G1899A, respectively; all adjusted p = 0.015). In conclusion, HBeAg-negative patients with high viral loads are strongly associated with PC mutations, particularly G1896A, A1846T/C, and G1899A. These exploratory findings provide regional NGS-based molecular evidence that established PC mutations may contribute to the coexistence of HBeAg negativity and continued high-level HBV replication in Indonesian patients. Larger studies incorporating broader virological and clinical comparison groups are required to determine the clinical significance of these findings.

Related

  1. A capsid hinge region in European hepatitis E virus links mutations to genotype, virion surface properties, and environmental circulation
    Samy Kasmi, Guillaume Sautrey, Cédric Hartard +7
    Applied and Environmental MicrobiologyPeer-reviewedCC BY-NC-ND 4.0Full textProteomics & metabolomicsStructural biologyHAL
  2. The hepatitis E virus ORF2 capsid protein, a cornerstone of viral persistence
    Pierre Bablon, Laura Corneillie, Laurence Cocquerel
    Médecine/SciencesPeer-reviewedCC BY 4.0Full textMicrobiologyHAL
  3. Promyelocytic leukemia (PML) suppresses hepatitis B virus cccDNA transcription through SUMOylation- and SMC5/6-dependent mechanisms
    J. Wu, F. Li, J. Ahodantin +2
    bioRxivPreprintAll rights reservedFull textImmunologybioRxiv
  4. Hepatitis C Virus NS2 Protein Is Phosphorylated by the Protein Kinase CK2 and Targeted for Degradation to the Proteasome
    Nathalie Franck, Jacques Le Seyec, Christiane Guguen-Guillouzo +1
    Journal of VirologyPeer-reviewedLicence not stated94 citedGeneral biologyHAL
  5. A prenatal testing program among future fathers in a Paris metropolitan area maternity reveals a high proportion of unmonitored chronic viral hepatitis B
    Pauline Penot, Annabel Desgrées Du Loû, Valérie-Anne Letembet +1
    HALPreprintCC BY-NC-ND 4.0Full textGeneral biologyHAL

Cite

BibTeXRIS
BibTeX
@article{wulandari2026hepatitis,
  title = {{Hepatitis B virus genome mutations in precore and basal core promoter regions among HBeAg-negative chronic hepatitis B patients with high viral load in Indonesia}},
  author = {Dewi Wulandari and Yan Mardian and Sunita and Kadek Aditya Darmayoga and Rindha Agustiani and Khoirunnisa and Youdiil Ophinni},
  journal = {PLOS One},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pone.0357754},
  url = {https://doi.org/10.1371/journal.pone.0357754},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Hepatitis B virus genome mutations in precore and basal core promoter regions among HBeAg-negative chronic hepatitis B patients with high viral load in Indonesia
AU  - Dewi Wulandari
AU  - Yan Mardian
AU  - Sunita
AU  - Kadek Aditya Darmayoga
AU  - Rindha Agustiani
AU  - Khoirunnisa
AU  - Youdiil Ophinni
PY  - 2026
DA  - 2026/09/15
JO  - PLOS One
DO  - 10.1371/journal.pone.0357754
UR  - https://doi.org/10.1371/journal.pone.0357754
AB  - Hepatitis B e antigen (HBeAg) is widely used as a marker for active HBV replication and serves as a surrogate for HBV DNA > 200,000 IU/mL to determine eligibility for tenofovir disoproxil fumarate (TDF) prophylaxis to prevent vertical transmission, according to WHO guidelines. However, some HBeAg-negative patients still harbor high viral loads. Mutations in the precore (PC) and basal core promoter (BCP) regions may reduce or abolish HBeAg expression without necessarily suppressing viral replication. Next-generation sequencing (NGS)-based characterization of these mutations remains limited in Indonesia. This study aimed to analyze the mutation prevalence in the BCP and PC regions associated with HBeAg negativity in Indonesian patients. We conducted a cross-sectional study of 32 chronic HBV treatment-naïve, unvaccinated patients with HBV DNA > 200,000 IU/mL (16 HBeAg-negative, 16 HBeAg-positive) at Cipto Mangunkusumo General Hospital. BCP and PC mutations were analyzed using NGS, classifying mutations as major (mutation frequency index [MFI] ≥20%) or minor (MFI 1– < 20%). Associations were analyzed using the Chi-square or Fisher’s exact test and p-values were adjusted using the Benjamini-Hochberg procedure. Among 29 major mutation sites, PC mutations A1846T/C and G1896A were more frequent in HBeAg-negative than HBeAg-positive patients (81.3% vs 6.3% and 75.0% vs 12.5%, respectively; all adjusted p = 0.019). Combined analysis showed higher mutation frequencies in HBeAg-negative patients (93.8%, 81.3%, and 62.5% for A1846T/C, G1896A, and G1899A, respectively; all adjusted p = 0.015). In conclusion, HBeAg-negative patients with high viral loads are strongly associated with PC mutations, particularly G1896A, A1846T/C, and G1899A. These exploratory findings provide regional NGS-based molecular evidence that established PC mutations may contribute to the coexistence of HBeAg negativity and continued high-level HBV replication in Indonesian patients. Larger studies incorporating broader virological and clinical comparison groups are required to determine the clinical significance of these findings.
SN  - 1932-6203
ER  -