An age-structured model of hepatitis B viral infection highlights the potential of different therapeutic strategies

TL;DR

This study develops an age-structured immune response model for hepatitis B, demonstrating that antiviral drugs targeting the viral life cycle are more effective than immune exhaustion therapies, and emphasizing early treatment and antibody therapies.

Contribution

The paper introduces a novel age-structured model incorporating both cellular and humoral immunity for HBV, validated with patient data and used to compare therapeutic strategies.

Findings

Drugs targeting viral life cycle are more effective than exhaustion therapy.

Antiviral treatment is most effective when viral load is declining.

Fast antibody production leads to viral clearance.

Abstract

Hepatitis B virus is a global health threat, and its elimination by 2030 has been prioritised by the World Health Organisation. Here we present an age-structured model for the immune response to an HBV infection, which takes into account contributions from both cell-mediated and humoral immunity. The model has been validated using published patient data recorded during acute infection. It has been adapted to the scenarios of chronic infection, clearance of infection, and flare-ups via variation of the immune response parameters. The impacts of immune response exhaustion and non-infectious subviral particles on the immune response dynamics are analysed. A comparison of different treatment options in the context of this model reveals that drugs targeting aspects of the viral life cycle are more effective than exhaustion therapy, a form of therapy mitigating immune response exhaustion. Our results suggest that antiviral treatment is best started when viral load is declining rather than in a flare-up. The model suggests that a fast antibody production rate always lead to viral clearance, highlighting the promise of antibody therapies currently in clinical trials.