In China and other highly HBV-endemic countries, mother-to-child transmission is the most important mode of HBV, and the prevention of mother-to-child transmission is the key to reduce new chronic HBV infections and control hepatitis B prevalence . Since the introduction of hepatitis B vaccine, the Chinese government has taken a number of measures to increase the full three-dose vaccine coverage and the birth dose coverage in children and, as the result, the high coverage of > 90% had been achieved for both in the early and late 2000s, respectively . Hepatitis B immunoglobulin as a supplement has also been used early in China for newborns born to HBsAg-positive mothers, and it was introduced into the national program integrating prevention of mother-to-child transmission of human immunodeficiency virus, syphilis, and HBV in 2012 . With economic and medical development, the Chinese government adopted increasingly interventions to control hepatitis B , such as safe injection practice, blood donation screening, management and treatment of chronic HBV-infected persons, and even extensive health education. These non-vaccine interventions can reduce risk contacts and even the probability of transmission following a risk contact, and their combined effects were integrated into our model by the transmission coefficient. There is no doubt that HBsAg prevalence will continue to decline steadily in China by maintaining current interventions, not only in children but also in the elderly, as predicted by our model. However, it is difficult for China to achieve the WHO’s target of 0.1% prevalence in children by 2030, if only current interventions are maintained. The results were robust according to our sensitivity analyses.
A small number of newborns are still infected with HBV despite the birth dose vaccine and hepatitis B immunoglobulin. The failure occurs mostly in newborns born to mothers with high viral load, as a result of intrauterine infections . Increasing evidences demonstrated that the use of antivirals in late pregnancy can interrupt this type of vertical transmission by 90%, and that the safety is acceptable . Based on this, the WHO updated its guideline in 2020, to recommend antiviral prophylaxis as an additional measure in eligible pregnant women for preventing HBV mother-to-child transmission and achieving the target of eliminating hepatitis B . An expert consensus on how to use the antiviral prophylaxis has been reached recently in the Chinese medical community . The routine antenatal test for HBV markers has earlier been implemented for all pregnant women in China, which ensures that the antiviral prophylaxis can be introduced and generalized as soon as possible. Our model predicted that the antiviral prophylaxis would play an important role to reduce HBsAg prevalence in children and achieve the WHO’s target by 2030. It may help China significantly shorten the period to meet the target of 0.1% prevalence in children if the successful interruption coverage is steadily scaled up. This finding is important for countries where mother-to-child transmission is the main mode of HBV and the birth dose vaccine and full vaccine series coverages for children have reached a very high level. However, this innovation alone is not sufficient for China to achieve the target on schedule. A comprehensive scale-up of available interventions, including current vaccine and non-vaccine measures and, especially, innovations like peripartum antiviral prophylaxis, is needed for China to achieve the WHO’s target of 0.1% prevalence in children by 2030. Although there is a limited space for China to further expand the birth dose vaccine and full vaccine series coverages in children, unremitting efforts are needed because a high HBsAg prevalence of 5.76% is still held by women of childbearing age in China , and vaccination starting at birth is the foundation of preventing HBV mother-to-child transmission .
China has a large number of chronic HBV carriers, which may maintain the virus circulation and a high HBsAg prevalence in the whole population for a long time. Natural HBV clearance is difficult in chronic infections, with an annual probability of around 1% . Current antivirals provide an opportunity that can keep HBV under control, slow the progression of cirrhosis, reduce incidence of liver cancer and improve long term survival, but it is not a cure because it cannot completely clear HBV from infected cells . Therefore, the treatment of patients with chronic hepatitis B played a very limited role in reducing HBsAg prevalence until now. Our model found that improving HBV clearance by treatment would be the most important factor to reduce HBsAg prevalence not only in the whole population but in children. However, the innovation is on the way.
There are two main limits in our study. First, the vaccination in adults was not considered in the model, due to the lack of data, which may lead to an estimate of longer time to achieve the target. However, this bias should be small, because adult hepatitis B vaccination in China follows the policy of “self-select and self-pay” and infected adults rarely develop chronic infection. Second, age-dependent mortalities of cirrhosis and hepatocellular carcinoma come from an international modelling study , which may be different from China. We adjusted the data by ± 50%, hoping to cover the situation in China. One-way sensitivity analyses found that changes of the two parameters have only a very small impact in the elderly and almost no impact in younger age groups.