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Updated: Aug 30, 2025

Author Spotlight: Advancements and Challenges in Hepatitis B Virus Detection
Published on: December 15, 2023
HBeAg-Negative/Anti-HBe-Positive Chronic Hepatitis B: A 40-Year-Old History
Ferruccio Bonino1, Piero Colombatto2, Maurizia R Brunetto1,2
1Institute of Biostructure and Bioimaging, National Research Council, Via De Amicis 95, 80145 Naples, Italy.
Insights
Hepatitis B e antigen (HBeAg) negative chronic hepatitis B is a global health issue. Early diagnosis and antiviral therapy are crucial for managing liver injury in HBeAg-negative patients.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) is the most common form of HBV-induced liver disease globally.
- Its prevalence has increased significantly over the past 40 years, posing a major healthcare burden.
- Understanding the dynamics of viral core protein expression is key to different clinical outcomes.
Purpose of the Study:
- To highlight the significance of HBeAg-negative CHB as a prevalent liver disease.
- To emphasize the role of persistent HBV replication in liver injury, even without HBeAg.
- To underscore the importance of early diagnosis and treatment.
Main Methods:
- Review of accumulated knowledge on HBV virology and clinic-pathologic outcomes.
- Analysis of the bimodal dynamics of viral core protein expression.
- Clinical practice guidelines for screening and diagnosis.
Main Results:
- HBeAg-negative CHB is the dominant form of chronic hepatitis B worldwide.
- Persistent HBV replication in the absence of HBeAg drives liver injury.
- Early detection of HBeAg-negative CHB is critical.
Conclusions:
- Screening for HBeAg-negative CHB is mandatory in HBV carriers.
- Antiviral therapy can effectively cure HBV-induced liver disease if initiated early.
- Timely intervention is essential for managing this prevalent liver condition.
Abstract:
Hepatitis B "e" antigen (HBeAg) negative chronic hepatitis B (CHB), 40 years since discovery in the Mediterranean area, has become the most prevalent form of HBV-induced liver disease worldwide and a major health care burden caused by HBV infection. A great deal of knowledge accumulated over the last decades provides consistent evidence on the bimodal dynamics of the expression of structural and non-structural forms of the viral core proteins which associate with different virologic and clinic-pathologic outcomes of HBV infection. In absence of serum HBeAg, the presence and persistence of HBV replication causes and maintains virus-related liver injury. Thus, in clinical practice it is mandatory to screen HBV carriers with HBeAg-negative infection for the early diagnosis of HBeAg-negative CHB since antiviral therapy can cure HBV-induced liver disease when started at early stages.

