Expert Insights | Dr. LechengYu: Is Mass Screening Necessary for HBV Infection in the General Population?

Editor's Note: Currently, the treatment rate for chronic hepatitis B (CHB) patients in China still needs improvement. China has a vast territory and a large population, raising the question of whether large-scale HBV screening is needed and if population-wide screening can help increase the diagnosis and treatment rate of CHB. This is not only a medical issue but also a complex social one. Recently, at the "15th Annual Conference on Challenges and Hot Topics in Antiviral Therapy for Chronic Viral Hepatitis," Dr. Lecheng Yu from the Eastern Theater General Hospital of the People's Liberation Army delivered a special report on "Whether HBV Infection Requires Mass Screening." In this report, he provided an in-depth analysis of the clinical significance and economic benefits of population-wide HBV screening, aiming to offer new evidence and perspectives for the formulation of HBV screening strategies. The following content summarizes the report for the benefit of fellow professionals and exchange of knowledge.

• Challenges Persist: Many Patients Remain, and the Situation Demands Attention

HBV infection is a global epidemic. According to the latest 2019 Global Burden of Disease (GBD) report^[1], the global prevalence of chronic HBV infection in 2019 was approximately 4.1% (3.7%-4.5%), which translates to about 316 million people (284-351 million). HBV-related diseases resulted in 555,000 deaths worldwide (487,000-630,000). Over the past decade, thanks to measures such as vaccination, antiviral therapy, and improved sanitation facilities, global efforts to control CHB have made significant progress. Compared to 1990, the prevalence of HBV infection in 2019 decreased by 31.3% (29.0%-33.9%), with a particularly notable decline of 76.8% (76.2%-77.5%) in children under the age of 5. However, regrettably, according to the ProGReSs model, a Markov model for monitoring the burden and transmission of HBV diseases, it is predicted that the global HBV infection rate will still be as high as 3.2% by 2022, with approximately 257.5 million chronic carriers.

Turning our attention to the domestic front, in recent years, with increased coverage of hepatitis B vaccines, the HBsAg positivity rate in China has significantly decreased, especially in children under 5 years of age^[2]. However, due to high historical prevalence, the HBsAg prevalence in the general population in China remains relatively high. There are approximately 75 million chronic HBV carriers (Figure 1), among whom approximately 20 million develop into CHB patients. The mortality from HBV-related liver diseases, particularly HBV-related liver cancer, remains higher than the global average (Figure 2). Therefore, China still bears the heaviest burden of HBV infection in the world. Without taking strong measures to further reduce the incidence and mortality rates, achieving the World Health Organization’s goal of eliminating viral hepatitis as a major public health threat by 2030 is not very realistic based on the current trend of CHB prevalence.

In 2016, the World Health Organization (WHO) set the goal of “eliminating viral hepatitis as a public health threat by 2030.” This goal aimed to reduce the number of new HBV infections by 95%, achieve a diagnosis rate of 90%, a treatment rate of 80%, and reduce related mortality by 65% compared to 2015. However, faced with a substantial population of approximately 75 million HBV carriers, China’s HBV infection diagnosis rate is only 22%, and the treatment rate is as low as 15%. It is evident that currently, only a small fraction of HBV-infected individuals in China receive diagnosis and treatment. Without proactive comprehensive screening, many HBV carriers may remain hidden within the general population, potentially becoming localized outbreaks.

• 2030 Goals vs. Low Diagnosis Rates: How to Break the Stalemate?

The urgency of the WHO’s 2030 goals for eliminating viral hepatitis as a public health threat is in stark contrast to the low diagnosis rate of HBV infection in the Chinese population. So, how can we address this complex situation? First, let’s analyze the reasons behind the low diagnosis rate of HBV infection, which can be summarized in three points:

1) Insufficient public awareness and importance: Many people, especially in rural and remote areas, lack knowledge about HBV infection and its dangers. Some patients who are aware of their HBV infection may have an indifferent attitude and neglect measures to prevent HBV transmission in their daily lives.

2) Inadequate social awareness campaigns about chronic HBV infection and its dangers: These campaigns have not reached every corner of society.

3) Lack of organized and planned proactive screening by health authorities.

In China’s vast population of chronic HBV carriers, most patients are unaware of their HBV status, making HBV infection a silent epidemic. Therefore, early detection through screening is essential to identify patients at risk of disease progression who require treatment. Early intervention can improve patient outcomes and also reduce the transmission of HBV within the population.

The resolution of the contradiction between WHO’s 2030 goals and China’s low diagnosis rate of HBV infection relies on population-wide HBV screening. Moreover, China’s medical technology, economic capability, and social conditions for implementing population-wide HBV infection screening are already mature and ready for action.

• In terms of medical technology:

The diagnosis of HBV infection primarily involves measuring five serum markers, and the reported results may vary depending on the HBV testing method used. As scholars gain a deeper understanding of HBV serum markers, HBV infection testing technology continues to advance and develop (see Figure 4).

In the 1970s, HBV testing was mainly conducted using colloidal gold assays (sandwich assays), which were qualitative tests. These methods were simple, quick, convenient, and cost-effective, but they had poor specificity, sensitivity, and high detection limits, particularly for samples with low concentrations, sometimes leading to missed diagnoses. In the 1980s, semi-quantitative ELISA assays were introduced, which were more cost-effective and relatively more sensitive and accurate than colloidal gold assays. These methods provided a rough estimate of the relative levels of HBV antigens and antibodies based on the S/CO ratio. Currently, quantitative testing using chemiluminescence assays is more commonly used. These assays offer high specificity and sensitivity and can dynamically reflect the natural course of the disease and the response to antiviral treatment.

• In terms of economic costs:

Currently, both ELISA and chemiluminescence assays for HBV testing are mature technologies with high sensitivity and specificity, especially chemiluminescence assays, which are the most widely used clinical method. In terms of pricing, domestic ELISA assays cost an average of 20-30 yuan per person, while Abbott or Roche chemiluminescence assays cost around 115 yuan per person. The cost of further testing for HBV DNA in individuals who test positive for HBsAg and/or anti-HBc, which is required for screening, is approximately 150 yuan per test, and high-sensitivity testing costs around 450 yuan per test. These costs are within an acceptable range.

• In terms of social conditions:

In recent years, China has made active and effective efforts and achievements in eliminating the public health threat of HBV in various aspects, including monitoring, prevention, screening, and drug assurance.

1) In terms of public awareness campaigns, there has been a considerable impact, and increasing the intensity of these campaigns can lead to even better results.

2) Regarding public health needs, the early detection, diagnosis, and treatment of HBV-related diseases are increasingly emphasized, and public understanding has improved. With improved mother-to-child transmission prevention techniques, the effectiveness of vaccine immunization, and good control of CHB progression through antiviral treatment, public understanding of HBV-infected individuals has significantly improved.

3) In terms of reagent reserves, there is an adequate supply of reagents and production capacity to support comprehensive screening.

4) In terms of the construction of the social healthcare service network, healthcare facilities are available in every corner of society.

5) In terms of transportation infrastructure, continuous improvement in transportation infrastructure has eliminated barriers to reaching remote and challenging areas.

• Optimizing the Strategy for Implementing Population-Wide HBV Screening

China has achieved significant success in vaccination, but relying solely on vaccination is insufficient to achieve WHO’s 2030 goals. Therefore, multiple decisive measures, including policy support, must be taken to advance HBV infection screening and diagnosis. Dr. Lecheng Yu suggests optimizing the strategy for population-wide HBV infection screening, integrating resources, and categorizing and zoning the implementation while identifying key areas.

01、Optimizing Policy Support and Resource Integration

At the national government level, there should be detailed unified planning and goals, with the priority being the coverage of diagnostic and treatment services. It is essential not only to reduce the medical burden on patients and improve the diagnostic and treatment capabilities of healthcare institutions and healthcare workers but also to better coordinate existing national plans and resources to establish a comprehensive HBV infection prevention and control system.

02、Categorizing and Zoning Implementation

Screening populations should be categorized, and screening areas should be zoned:

1) Prioritize high-risk populations for screening, followed by intermediate-risk populations, and conduct rapid screening for low-risk populations. High-risk and intermediate-risk populations should be screened for HBsAg, anti-HBs, and anti-HBc. Low-risk populations can use on-site rapid screening with HBsAg colloidal gold test strips. 2) Implement screening in urban areas first, followed by convenient rural areas, and address remote areas opportunistically.

03、Identifying Key Areas

Firstly, focus on the main transmission routes and key populations. Mother-to-child transmission is the most significant transmission route for HBV in China, and preventing HBV mother-to-child transmission is key to reducing new infections. Projects like the “HBV Mother-to-Child Zero Transmission Project” (Little Shell Project) initiated by Dr. Jinlin Hou’s team at Southern Medical University Southern Hospital in 2015 have conducted “comprehensive screening” of subpopulations at high risk of mother-to-child transmission, guiding the implementation of “full blockade” of HBV mother-to-child vertical transmission.

Secondly, intensify awareness campaigns to eliminate HBV discrimination and promote population-wide HBV screening simultaneously. Monitor the effectiveness of actions and establish a “follow-up mechanism” to ensure the successful implementation of population-wide HBV screening.

Furthermore, update guidelines to provide recommendations for HBV screening in populations in guidelines and policies. The latest version of the “Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition)” has further clarified the necessity of HBsAg screening in the general population. In the 2019 edition of the guidelines, the recommendation was to “encourage” HBsAg, anti-HBc, and anti-HBs screening during routine health check-ups or medical visits that do not involve admission to kindergarten, school, or employment. In the 2022 edition, “encourage” has been changed to “should,” and the use of HBV DNA testing for screening is emphasized whenever possible. The new guidelines take a significant step towards “universal treatment” for chronic HBV infection, which helps reduce HBV transmission risks and supports “universal prevention.”

In summary, to achieve WHO’s 2030 goals, three “universals” are essential in HBV prevention and control: 1) Universal vaccination: In addition to newborn vaccination, high and intermediate-risk populations should also be actively vaccinated. 2) Universal population-wide screening: Emulating the spirit of the Little Shell Project, discover and actively block more potential transmission chains. 3) Universal treatment of the population: Patients eligible for antiviral treatment should all receive antiviral treatment.

In conclusion, due to various factors, the diagnosis and treatment rates of chronic HBV infection in the Chinese population are low. To achieve WHO-2030 goals, an intensive population-wide HBV infection screening is urgently needed. In China, the medical technology, economic capability, and social conditions for implementing population-wide HBV infection screening are largely ready, and what remains is the necessary administrative management and regulatory support. It is recommended to further promote guideline updates and the Little Shell Project to establish guidelines and regulatory basis for the “optimization of policy support, resource integration, categorization and zoning, and the identification of key areas” in the strategy for population-wide screening. Continuous guidance and the cultivation of a social atmosphere of human care are essential to eliminate discrimination against HBV and ensure the effective implementation of population-wide screening.

TAG: Insights; HBV