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Updated: Aug 25, 2025
Author Spotlight: Advancements and Challenges in Hepatitis B Virus Detection
Published on: December 15, 2023
[Natural history and disease progression of chronic hepatitis B virus infection]
1Department of Microbiology & Infectious Disease Center, Peking University School of Basic Medical Sciences, Beijing 100191, China.
Insights
This study analyzes chronic hepatitis B virus (HBV) infection stages in 760 patients. Findings suggest HBeAg-negative chronic hepatitis B (CHB) may arise from HBeAg-positive CHB patients, not solely inactive carriers.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Chronic hepatitis B virus (HBV) infection affects millions globally, with complex natural history and disease progression.
- Understanding the distinct phases of chronic HBV infection is crucial for effective management and treatment strategies.
Purpose of the Study:
- To elucidate the natural history and disease progression of chronic HBV infection.
- To analyze a large single-center cohort to refine understanding of HBV infection phases.
Main Methods:
- Retrospective analysis of 760 patients with chronic HBV infection who underwent liver biopsy between 2014 and 2020.
- Categorization of patients into four disease progression statuses based on hepatitis B e antigen (HBeAg) status and pathology: HBeAg-positive immune tolerance, HBeAg-positive immune active, HBeAg-negative inactive carrier, and HBeAg-negative immune reactive (CHB).
- Comparison of demographic, laboratory, and histological data across the four disease stages, with age differences assessed using the Mann-Whitney U test.
Main Results:
- The study included 760 patients (median age 29 years), with 197 underage and 563 adults; 456 males and 304 females.
- Patients were classified into four phases: HBeAg-positive immune tolerance (173), HBeAg-positive immune active (329), HBeAg-negative inactive carrier (95), and HBeAg-negative CHB (163).
- HBeAg-negative CHB patients (median age 37) were older than HBeAg-positive immune active CHB patients (median age 24, P < 0.001) but similar in age to HBeAg-negative inactive carriers (median age 39, P=0.240).
Conclusions:
- The findings suggest that HBeAg-negative CHB patients may not exclusively originate from HBeAg-negative chronic HBV infection (inactive carriers).
- A subset of HBeAg-negative CHB patients might develop from HBeAg-positive CHB patients who have achieved HBeAg clearance or seroconversion while remaining in an immune-active state.
- This challenges traditional models of HBV disease progression and highlights the need for nuanced understanding of immune dynamics in chronic HBV.
Objective:
To better understand and revise the natural history and disease progression of chronic hepatitis B virus (HBV) infection through analysis of a single-center large-scale cohort of indivi-duals with chronic HBV infection.
Methods:
Patients with chronic HBV infection who had undergone liver biopsy in the Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital from January 2014 to October 2020 were retrospectively recruited. Based on patient's hepatitis B e antigen (HBeAg) states and pathologic diagnosis, they were categorized into four disease progression statuses (or phases according to the old-terminology in the updated guidelines of chronic hepatitis B (CHB), such as European Association for the Study of the Liver (EASL) 2017, Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection: HBeAg-positive chronic HBV infection (immune tolerance), HBeAg-positive CHB (immune active HBeAg positive), HBeAg-negative chronic HBV infection (inactive carrier), and HBeAg-negative CHB (immune reactive HBeAg negative). Then the demographic, laboratory tests and liver histological results of the patients in different disease progression stages were compared. Age differences between the two groups were evaluated using Mann-Whitney U test.
Results:
A total of 760 eligible patients with a median age of 29 (interquartile range: 16-39) years were enrolled. Among them, 197 were underage individuals (age < 18 years) and 563 were adults; and 456 were males and 304 females. According to the pathological diagnosis, the patients were classified, and in each of the above four natural disease phases there were 173, 329, 95, and 163 individuals, respectively. Further comparison of the ages of the patients of the four disease progression statuses revealed that patients of HBeAg-negative CHB had a median age at 37 years, which was reasonably higher than those with HBeAg-positive CHB in immune active phase (37 vs. 24 years, P < 0.001), but was relatively younger than those with HBeAg-negative chronic HBV infection (37 vs. 39 years, P= 0.240).
Conclusion:
According to this study, it could be speculated that HBeAg-negative CHB patients probably not all reactivate from individuals of HBeAg-negative chronic HBV infection. Instead, certain HBeAg-negative CHB patients may also come from HBeAg-positive CHB patients who have undergone HBeAg clearance or seroconversion and still remain in the immune active state.
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