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Updated: Jan 6, 2026
Author Spotlight: Advancements and Challenges in Hepatitis B Virus Detection
Published on: December 15, 2023
Modeling covalently closed circular DNA dynamics in assessing chronic hepatitis B prognosis
Qiulin Huang1, Qiang Li2, Zaitang Huang3
1School of Mathematics and Statistics, Southwest University, Chongqing, 400715, China.
Insights
This study introduces a mathematical model to predict hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) levels. The model accurately forecasts serologic negative conversion (SNC) in chronic hepatitis B (CHB) patients, aiding treatment strategies.
Area of Science:
- Virology
- Mathematical Biology
- Hepatology
Background:
- Covalently closed circular DNA (cccDNA) persistence in HBV-infected hepatocytes drives chronic hepatitis B (CHB) pathogenesis.
- Hepatitis B surface antigen (HBsAg) levels serve as a surrogate marker for cccDNA quantification.
Purpose of the Study:
- To develop and validate a mathematical model for predicting cccDNA kinetics in HBV-infected hepatocytes.
- To assess the model's accuracy in forecasting serologic negative conversion (SNC) in CHB patients.
Main Methods:
- Development of a mathematical model to simulate cccDNA dynamics.
- Analysis of clinical data from 96 newly treated CHB patients.
- Calculation of the basic reproduction rate and identification of backward bifurcation.
Main Results:
- The mathematical model demonstrated a high concordance rate (93.75%) with clinical outcomes for SNC prediction.
- Baseline HBsAg, HBV DNA, and hepatitis e surface antigen levels significantly influence model accuracy.
- Backward bifurcation was identified in the cccDNA kinetics model.
Conclusions:
- The proposed mathematical model effectively predicts SNC in CHB patients.
- The model's accuracy is influenced by baseline viral markers.
- This model can assist in designing clinical withdrawal indicators for CHB treatment.
Abstract:
The persistence of covalently closed circular DNA (cccDNA) in the nuclei of HBV-infected hepatocytes plays a critical role in the pathogenesis of chronic hepatitis B (CHB), and hepatitis B surface antigen (HBsAg) levels can be considered a surrogate marker for cccDNA quantification. In this paper, a mathematical model is proposed to mimic cccDNA kinetics in infected hepatocytes, and the basic reproduction rate of cccDNA is obtained. It is found that the backward bifurcation occurs. Importantly, the model predictions match well the clinical data from 96 newly treated CHB patients, collected at the authors' hospitals. Specifically, 18 patients (23.96 %) achieved HBsAg serologic negative conversion (SNC), excluding 5 patients with serologic relapse. Ten patients were predicted to be uncertain, including two clinically confirmed patients with SNC. Excluding the uncertain patients, our model gives a concordance rate of 93.75 % (15/16). Our results suggest that the baseline HBsAg, HBV DNA and hepatitis e surface antigen statuses are the major factors related to the accuracy of the model for the prediction of negative conversion. Therefore, our model is helpful to design effective clinical withdrawal indicators.
