Deep sequencing identifies hepatitis B virus core protein signatures in chronic hepatitis B patients

Meike H. van der Ree, Louis Jansen, Matthijs R. A. Welkers, Hendrik W. Reesink, K. Anton Feenstra, Neeltje A. Kootstra*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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BACKGROUND: We aimed to identify HBc amino acid differences between subgroups of chronic hepatitis B (CHB) patients.

METHODS: Deep sequencing of HBc was performed in samples of 89 CHB patients (42 HBeAg positive, 47 HBeAg negative). Amino acid types were compared using Sequence Harmony to identify subgroup specific sites between HBeAg-positive and -negative patients, and between patients with combined response and non-response to peginterferon/adefovir combination therapy.

RESULTS: We identified 54 positions in HBc where the frequency of appearing amino acids was significantly different between HBeAg-positive and -negative patients. In HBeAg negative patients, 22 positions in HBc were identified which differed between patients with treatment response and those with non-response. The fraction non-consensus sequence on selected positions was significantly higher in HBeAg-negative patients, and was negatively correlated with HBV DNA and HBsAg levels.

CONCLUSIONS: Sequence Harmony identified a number of amino acid changes associated with HBeAg-status and response to peginterferon/adefovir combination therapy.

Original languageEnglish
Pages (from-to)213-225
Number of pages13
JournalAntiviral research
Early online date16 Aug 2018
Publication statusPublished - Oct 2018


  • Chronic hepatitis B
  • Deep sequencing
  • HBeAg status
  • Hepatitis B virus core protein
  • Treatment response


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