High prevalence and significance of hepatitis D virus infection among treatment-naïve HBsAg-positive patients in Northern Vietnam

PLoS One. 2013 Oct 18;8(10):e78094. doi: 10.1371/journal.pone.0078094. eCollection 2013.


Background: Hepatitis D virus (HDV) infection is considered to cause more severe hepatitis than hepatitis B virus (HBV) monoinfection. With more than 9.5 million HBV-infected people, Vietnam will face an enormous health burden. The prevalence of HDV in Vietnamese HBsAg-positive patients is speculative. Therefore, we assessed the prevalence of HDV in Vietnamese patients, determined the HDV-genotype distribution and compared the findings with the clinical outcome.

Methods: 266 sera of well-characterized HBsAg-positive patients in Northern Vietnam were analysed for the presence of HDV using newly developed HDV-specific RT-PCRs. Sequencing and phylogenetic analysis were performed for HDV-genotyping.

Results: The HDV-genome prevalence observed in the Vietnamese HBsAg-positive patients was high with 15.4% while patients with acute hepatitis showed 43.3%. Phylogenetic analysis demonstrated a predominance of HDV-genotype 1 clustering in an Asian clade while HDV-genotype 2 could be also detected. The serum aminotransferase levels (AST, ALT) as well as total and direct bilirubin were significantly elevated in HDV-positive individuals (p<0.05). HDV loads were mainly low (<300 to 4.108 HDV-copies/ml). Of note, higher HDV loads were mainly found in HBV-genotype mix samples in contrast to single HBV-infections. In HBV/HDV-coinfections, HBV loads were significantly higher in HBV-genotype C in comparison to HBV-genotype A samples (p<0.05).

Conclusion: HDV prevalence is high in Vietnamese individuals, especially in patients with acute hepatitis B. HDV replication activity showed a HBV-genotype dependency and could be associated with elevated liver parameters. Besides serological assays molecular tests are recommended for diagnosis of HDV. Finally, the high prevalence of HBV and HDV prompts the urgent need for HBV-vaccination coverage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bilirubin / metabolism
  • Female
  • Genotype
  • Hepatitis B Surface Antigens / metabolism*
  • Hepatitis D / epidemiology*
  • Hepatitis D / immunology
  • Hepatitis D / metabolism
  • Hepatitis D / virology*
  • Hepatitis Delta Virus / immunology
  • Hepatitis Delta Virus / pathogenicity*
  • Humans
  • Male
  • Middle Aged
  • Prevalence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vietnam / epidemiology
  • Young Adult


  • Hepatitis B Surface Antigens
  • Bilirubin

Grant support

B.T. Sy was supported by a scholarship from project 322 of Vietnam Ministry of Education and Training, Vietnam. The authors acknowledge the support by the Deutsche Forschungsgemeinschaft (DFG) and Open Access Publishing Fund of Tuebingen University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.