Hepatitis B prevention: Can we learn from the response to HIV/AIDS?

Background International Sustainable Development Goals (SDGs) for elimination of hepatitis B virus (HBV) infection set ambitious targets for 2030. In African populations, infant immunisation has been fundamental to reducing incident infections in children, but overall population prevalence of chronic hepatitis B (CHB) infection remains high. In high-prevalence populations, adult catch-up vaccination has sometimes been deployed, but an alternative Test and Treat (T&T) approach could be used as an intervention to interrupt transmission. Universal T&T has not been previously evaluated as a population intervention for HBV infection, despite high-profile data supporting its success with human immunodeficiency virus (HIV). Methods and findings We set out to investigate the relationship between prevalence of HBV infection and exposure in Africa, undertaking a systematic literature review in November 2019. We identified published seroepidemiology data representing the period 1995–2019 from PubMed and Web of Science, including studies of adults that reported prevalence of both hepatitis B surface antigen (HBsAg; prevalence of HBV infection) and antibody to hepatitis B core antigen (anti-HBc; prevalence of HBV exposure). We identified 96 studies representing 39 African countries, with a median cohort size of 370 participants and a median participant age of 34 years. Using weighted linear regression analysis, we found a strong relationship between the prevalence of infection (HBsAg) and exposure (anti-HBc) (R2 = 0.45, p < 0.001). Region-specific differences were present, with estimated CHB prevalence in Northern Africa typically 30% to 40% lower (p = 0.007) than in Southern Africa for statistically similar exposure rates, demonstrating the need for intervention strategies to be tailored to individual settings. We applied a previously published mathematical model to investigate the effect of interventions in a high-prevalence setting. The most marked and sustained impact was projected with a T&T strategy, with a predicted reduction of 33% prevalence by 20 years (95% CI 30%–37%) and 62% at 50 years (95% CI 57%–68%), followed by routine neonatal vaccination and prevention of mother to child transmission (PMTCT; at 100% coverage). In contrast, the impact of catch-up vaccination in adults had a negligible and transient effect on population prevalence. The study is constrained by gaps in the published data, such that we could not model the impact of antiviral therapy based on stratification by specific clinical criteria and our model framework does not include explicit age-specific or risk-group assumptions regarding force of transmission. Conclusions The unique data set collected in this study highlights how regional epidemiology data for HBV can provide insights into patterns of transmission, and it provides an evidence base for future quantitative research into the most effective local interventions. In combination with robust neonatal immunisation programmes, ongoing PMTCT efforts, and the vaccination of high-risk groups, diagnosing and treating HBV infection is likely to be of most impact in driving advances towards elimination targets at a population level.
Anna McNaughton and colleagues study the epidemiology of hepatitis B virus in African countries, and assess strategies to reduce disease burden.
Author summary Why was this study done? Hepatitis B virus (HBV) infection is a major global health problem, with an estimated 290 million infections worldwide; international targets set the challenge for this public health threat to be eliminated by 2030. Administering HBV vaccine to babies is a very successful way to prevent new infections, but previous studies have shown that this strategy will take many decades to bring about elimination targets. We set out to investigate other approaches that can be used in combination with the infant vaccination schedule, using data from a meta-analysis and modelling the impact of vaccinating older children and adults, or enhancing testing and treatment (T&T) of existing HBV infections. What did the researchers do and find? We undertook a review and meta-analysis of all the published data describing the frequency of HBV infection, as well as the frequency of exposure to HBV infection in African populations, working with data from 96 studies published between 1995 and 2019. Using these data, we demonstrated a significant relationship between exposure and infection (overall p < 0.001) and identified differences between geographic regions. Using an existing mathematical model, our findings suggest that vaccinating older age groups has negligible sustained effect on HBV rates in a population, but universal T&T of HBV is predicted to have a substantial impact. What do these findings mean? Our results show different patterns of HBV infection and transmission in different regions of Africa, illustrating that interventions may need to be tailored according to the specific setting. We have demonstrated that vaccination campaigns targeting older children and adults are unlikely to be an effective use of resources in most African populations, and that resources are better diverted to improving diagnosis and treatment of existing infections. The study is limited by gaps in existing data, such that many populations in Africa are poorly represented. Our conclusions are drawn from the output of a model and will need to be validated in clinical practice.