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Updated: Dec 24, 2025
Author Spotlight: Advancements and Challenges in Hepatitis B Virus Detection
Published on: December 15, 2023
Use of hepatitis B virus core-related antigen to evaluate natural history of chronic hepatitis B
Henry Lik Yuen Chan1, Satoshi Yasuda2, Grace Lai Hung Wong1
1Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
Insights
Hepatitis B core-related antigen (HBcrAg) effectively stages chronic hepatitis B natural history. It helps identify HBeAg-positive and HBeAg-negative patients with active disease, aiding in disease management.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Hepatitis B core-related antigen (HBcrAg) correlates with viral markers in chronic hepatitis B.
- Its role in defining the natural history of chronic hepatitis B is not well understood.
Purpose of the Study:
- To investigate the utility of HBcrAg in defining different phases of chronic hepatitis B natural history.
- To assess HBcrAg's ability to differentiate disease stages and patient groups.
Main Methods:
- Analysis of serum samples from longitudinal cohorts in Hong Kong and Japan.
- Measurement of viral markers including HBcrAg, HBV DNA, and HBsAg.
- Categorization of patients into six groups based on hepatitis B e antigen (HBeAg) status and disease phase.
Main Results:
- HBcrAg levels correlated with HBV DNA and HBsAg in both HBeAg-positive and negative patients.
- An HBcrAg cut-off of ≥6.0 log U/mL differentiated HBeAg-positive from HBeAg-negative patients (AUC 0.99).
- HBcrAg ≥4.0 log U/mL differentiated active hepatitis from infection in HBeAg-negative patients (AUC 0.81).
Conclusions:
- HBcrAg is a valuable marker for staging the natural history of chronic hepatitis B.
- HBcrAg aids in identifying HBeAg-positive patients and HBeAg-negative patients with active disease.
- HBcrAg levels decrease significantly during HBeAg seroconversion and are undetectable in a majority of patients with resolved infection or seroclearance.
Background And Aim:
Hepatitis B core-related antigen (HBcrAg) has been shown to correlate with various viral markers in chronic hepatitis B, but its role in defining natural history is not well studied. We aimed to investigate the use of HBcrAg to define different phases of chronic hepatitis B.
Methods:
Stored residual serum samples from longitudinal cohorts of chronic hepatitis B patients in Hong Kong and Japan were studied. Viral markers were measured in three serial serum samples for each patient. Patients were divided into six groups for analysis: hepatitis B e antigen (HBeAg)-positive chronic infection (EPI), HBeAg-positive chronic hepatitis (EPH), HBeAg seroconversion (ES), HBeAg-negative chronic hepatitis (ENH), HBeAg-negative chronic infection (ENI), and HBsAg seroclearance (SS).
Results:
In total, 166 patients followed up for 100 (76-113) months were included. HBcrAg was correlated with hepatitis B virus DNA and HBsAg levels in both HBeAg-positive and HBeAg-negative patients. HBcrAg cut-off of ≥ 6.0 log U/mL could best differentiate HBeAg-positive from HBeAg-negative patients (area under receiver operating characteristic curve of 0.99, P < 0.001). HBcrAg could not differentiate patients in EPI and EPH phases, but HBcrAg declined dramatically at HBeAg seroconversion. In HBeAg-negative patients, HBcrAg ≥ 4.0 log U/mL could best differentiate ENH from ENI (area under receiver operating characteristic curve of 0.81; P < 0.001), with high specificity (81.6%) but only moderate sensitivity (65.7%) at baseline. Undetectable HBcrAg was found in 17%, 63%, and 89% patients in ENH, ENI, and SS groups at the last visit, respectively.
Conclusions:
HBcrAg provides useful information to stage the natural history of chronic hepatitis B, particularly identifying HBeAg-positive patients and HBeAg-negative patients with active disease.
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