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Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
Published on: February 1, 2017
Deep sequencing identifies hepatitis B virus core protein signatures in chronic hepatitis B patients
Meike H van der Ree1, Louis Jansen1, Matthijs R A Welkers2
1Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands; Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands.
Insights
Amino acid differences in hepatitis B core antigen (HBc) were identified between chronic hepatitis B (CHB) patient subgroups. These variations correlate with HBeAg status and treatment response, offering insights into disease progression.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Chronic hepatitis B (CHB) is a significant global health concern.
- Understanding viral protein variations is crucial for managing CHB.
- Hepatitis B e antigen (HBeAg) status and treatment response are key clinical indicators in CHB.
Purpose of the Study:
- To identify amino acid differences in the hepatitis B core antigen (HBc) between CHB patient subgroups.
- To correlate HBc amino acid variations with HBeAg serostatus.
- To investigate the association between HBc amino acid changes and response to combination antiviral therapy.
Main Methods:
- Deep sequencing of the HBc gene was performed on samples from 89 CHB patients.
- Sequence Harmony software was utilized for comparative amino acid analysis.
- Patients were stratified based on HBeAg positivity/negativity and response to peginterferon/adefovir therapy.
Main Results:
- Significant differences in amino acid frequencies at 54 HBc positions were found between HBeAg-positive and -negative patients.
- Twenty-two HBc positions showed differential amino acid usage between treatment responders and non-responders in HBeAg-negative patients.
- A higher proportion of non-consensus sequences at specific HBc sites was observed in HBeAg-negative patients, negatively correlating with HBV DNA and HBsAg levels.
Conclusions:
- Sequence Harmony effectively identified amino acid alterations in HBc linked to HBeAg status.
- Specific HBc amino acid changes are associated with treatment outcomes in CHB patients receiving combination therapy.
- These findings contribute to a deeper understanding of HBc protein's role in CHB pathogenesis and treatment response.
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.
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