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

ABSTRACT: Hepatitis B virus (HBV) 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 leads to viral clearance, highlighting the promise of antibody therapies currently in clinical trials.

SUBMITTER: Fatehi F

PROVIDER: S-EPMC8786976 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Fatehi Farzad F Bingham Richard J RJ Stockley Peter G PG Twarock Reidun R

Scientific reports 20220124 1

Hepatitis B virus (HBV) 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 vari ...[more]

PMID: 35075156

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Project description:The potential impact of increasing test-and-treat coverage on hepatitis B virus (HBV) infection remains unclear in China. The objective of this study was to develop a dynamic compartmental model at a population level to estimate the long-term effect of this strategy.Based on the natural history of HBV infection and 3 serosurvey data of hepatitis B in China, we proposed an age- and time-dependent discrete model to predict the number of new HBV infection, the number of chronic HBV infection, and the number of HBV-related deaths for the time from 2018 to 2050 under 5 different test-and-treat coverage and compared them with current intervention policy.Compared with current policy, if the test-and-treat coverage was increased to 100% since 2018, the numbers of chronic HBV infection, new HBV infection, and HBV-related deaths in 2035 would be reduced by 26.60%, 24.88%, 26.55%, respectively, and in 2050 it would be reduced by 44.93%, 43.29%, 43.67%, respectively. In contrast, if the test-and-treat coverage was increased by 10% every year since 2018, then the numbers of chronic HBV infection, new HBV infection, and HBV-related deaths in 2035 would be reduced by 21.81%, 20.10%, 21.40%, respectively, and in 2050 it would be reduced by 41.53%, 39.89%, 40.32%, respectively. In particular, if the test-and-treat coverage was increased to 75% since 2018, then the annual number of HBV-related deaths would begin to decrease from 2018. If the test-and-treat coverage was increased to above 25% since 2018, then the hepatitis B surface antigen (HBsAg) prevalence for population aged 1 to 59 years in China would be reduced to below 2% in 2035. Our model also showed that in 2035, the numbers of chronic HBV infection and HBV-related deaths in 65 to 69 age group would be reduced the most (about 1.6 million and 13 thousand, respectively).Increasing test-and-treat coverage would significantly reduce HBV infection in China, especially in the middle-aged people and older people. The earlier the treatment and the longer the time, the more significant the reduction. Implementation of test-and-treat strategy is highly effective in controlling hepatitis B in China.

Project description:BackgroundThe epidemiological pattern of hepatitis A infection has shown dynamic changes in many parts of the world due to improved socio-economic conditions and the accumulation of seronegative subjects, which leads to possible outbreaks and increased morbidity rate. In Tunisia, the epidemiological status of hepatits A virus is currently unknown. However, over the past years higher numbers of symptomatic hepatitis A virus infection in school attendants and several outbreaks were reported to the Ministry of Health, especially from regions with the lowest socio-economic levels in the country. The aim of this study was to investigate the current seroprevalence of hepatitis A virus antibodies in central-west Tunisia and assess the impact of hepatitis A virus vaccination on hepatitis A epidemiology.MethodsSerum samples from 1379 individuals, aged 5-75 years, were screened for hepatitis A virus antibodies. Adjusted seroprevalence, incidence and force of infection parameters were estimated by a linear age structured SEIR (Susceptible-Exposed-Infectious-Recovered) compartmental model. A vaccine model was then constructed to assess the impact on hepatitis A virus epidemiology of 3 scenarios of vaccination strategies: one dose at 12-months of age, one dose at 6-years and one dose at 12-months and another at 6-years of age during 6 years.ResultsA rapid increase in anti-hepatitis A virus seroprevalence was noted during infancy and adolescence: 47% of subjects under 10-years-old are infected; the prevalence increases to 77% at 15-years and reaches 97% in subjects aged 30-years. The force of infection is highest between 10 and 30-years of age and the incidence declines with increasing age. The vaccine model showed that the 3-scenarios lead to a significant reduction of the fraction of susceptibles. The two doses scenario gives the best results. Single-dose vaccination at 6-years of age provides more rapid decrease of disease burden in school-aged children, as compared to single-dose vaccination at 12-months, but keeps with a non-negligible fraction of susceptibles among children < 6-years.ConclusionsOur study confirms the epidemiological switch from high to intermediate endemicity of hepatitis A virus in Tunisia and provides models that may help undertake best decisions in terms of vaccinations strategies.

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

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

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