Editor's Note: China has historically been a high-prevalence area for Hepatitis B virus (HBV) infection, with a hepatitis B surface antigen (HBsAg) prevalence rate of 9.7% in 1992. Comprehensive strategies, including the hepatitis B vaccine program for newborns (HepB), with a strong emphasis on timely administration of the birth dose and completion of the three-dose schedule, have significantly reduced mother-to-child transmission and early childhood HBV infections. With the significant reduction in the cost of antiviral drugs, treatment accessibility and affordability have greatly improved. From July 20 to 21, the "2024 World Hepatitis Day Campaign and Hepatitis Elimination Action Conference" was held in Beijing. Dr. Jidong Jia from Beijing Friendship Hospital ,Capital Medical University delivered a keynote speech titled "Progress and Challenges in the Prevention and Treatment of Hepatitis B in China," where he systematically explained the progress made, the challenges faced, and the urgent actions needed in the prevention and treatment of hepatitis B in China.Progress in Hepatitis B Prevention and Treatment in China
1. Significant Reduction in Mother-to-Child Transmission
Since mother-to-child transmission and early childhood HBV infection are major contributors to high HBsAg prevalence rates, China launched the HepB program in 1992, recommending the first dose of the hepatitis B vaccine (TBD) within 24 hours of birth, followed by the second and third doses at one and six months, respectively (Figure 1). As the coverage rate of the full three-dose schedule and the timely administration of the birth dose increased, the HBsAg prevalence rate has steadily declined over the past few decades.
For newborns of HBsAg-positive mothers, especially those also positive for hepatitis B e-antigen (HBeAg), administering hepatitis B immunoglobulin (HBIg) at birth can further reduce the rate of mother-to-child transmission. A review by Professor Jia Jidong’s team showed that China’s mother-to-child transmission rate of HBV was among the lowest in the Asia-Pacific region (2010-2020). In a large-scale demonstration project, passive-active immunization achieved a 98.3% success rate in blocking HBV mother-to-child transmission, with success rates of 95.24% and 100% for HBeAg-positive and HBeAg-negative mothers, respectively.
In 2011, China launched a triple elimination program for HIV, syphilis, and HBV mother-to-child transmission, providing supplementary HBsAg screening for all pregnant women and HBIg for newborns of HBsAg-positive mothers. Preliminary results showed that the HBV mother-to-child transmission rate decreased to 0.9% among 4,112 babies born to HBsAg-positive mothers, 30% of whom were HBeAg-positive. A recent study indicated that for newborns of HBsAg-positive, HBeAg-negative mothers, timely administration of the first HepB dose at birth and completion of the three-dose schedule (with a failure rate of 0%) was as effective in preventing mother-to-child transmission as standard passive-active immunization (with a failure rate of 0.1%), offering a viable alternative in environments where HBIg is expensive or in limited supply.
Additionally, the latest real-world data from Dr. Jinlin Hou’s team showed that in the “Little Shell” project, involving 178 medical institutions and tens of thousands of pregnant women, the HBV mother-to-child transmission rate significantly decreased to 0.23% overall. In the second phase of the project, the group with high adherence saw a further reduction in the transmission rate to 0.16%, much lower than the 3.16% in the low-adherence group. By the third phase, the high-adherence group achieved an extremely low transmission rate of 0.03%, compared to 1.91% in the low-adherence group.
2. Continuous Decline in HBsAg Positivity Rate
Thanks to China’s relentless efforts in combating HBV, the HBsAg positivity rate in the population has continued to decrease significantly. A modeling study estimated that in 2022, the HBsAg prevalence rate was 5.6% in the general population and 0.1% in children under five.
3. Reduced Risk of Liver Cancer and Liver Disease
A 30-year follow-up study in China showed that neonatal hepatitis B vaccination significantly reduced the HBsAg prevalence rate from childhood to adolescence, thereby lowering the risk of primary hepatocellular carcinoma (HCC) and other liver diseases among rural youth in China.
4. Development and Updates of Guidelines
In the field of chronic hepatitis B (CHB) treatment, clinical research has provided high-quality evidence for CHB guidelines. Over the past twenty years, liver disease research and publications in China have steadily increased. To improve CHB treatment rates, the Chinese Medical Association issued the first “Guidelines for the Prevention and Treatment of Chronic Hepatitis B” in 2005, followed by updates in 2010, 2015, 2019, and 2022.
5. Progress in Antiviral Treatment
Antiviral treatment can improve clinical outcomes for CHB patients, including those with cirrhosis. A study conducted byDr. Wen Xie and Dr. Jidong Jia’s team showed that 120 weeks of entecavir antiviral treatment led to “recompensation” in 56% of patients with decompensated hepatitis B cirrhosis and established criteria for evaluating liver function improvement: stable and improved liver function defined as MELD<10 or liver function indices in CTP grade A (ALB>35 g/L, INR<1.50, TBIL<34 μmol/L).
Recent research by Dr. Hong You and Dr. Jidong Jia’s team demonstrated that long-term antiviral therapy can reverse liver fibrosis and reduce clinical endpoint events, including decompensation, HCC, liver transplantation, and death.
Another study by the team of Dr. Jidong Jia, Hong You, and Fengmin Lu showed that long-term antiviral treatment could reduce the transcriptional activity of integrated HBV DNA.
Thanks to advances in CHB treatment in China, the incidence and mortality rates of HCC have declined over the past two decades, with China accounting for 42% of the new HCC cases worldwide in 2020.
To increase CHB treatment rates, China’s latest “Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition)” further expanded the indications for antiviral therapy. The guidelines recommend initiating antiviral therapy for anyone with CHB cirrhosis or a family history of HCC, or those aged >30 years. For patients with clinically diagnosed compensated and decompensated hepatitis B cirrhosis, antiviral treatment is recommended regardless of ALT and HBV DNA levels or HBeAg status, as long as they are HBsAg-positive. The WHO 2024 guidelines’ treatment indications cover >50% of HBsAg-positive individuals, whereas the 2022 edition of the chronic hepatitis B prevention and treatment guidelines have further broadened the coverage of treatment indications.
Challenges in Hepatitis B Prevention and Treatment in China
1. Heavy HBV Disease Burden
According to the latest data from the World Health Organization (WHO), as of 2022, China remains one of the 10 countries accounting for two-thirds of the global burden of hepatitis B, ranking first in both the number of infections (79,700,000) and percentage (31.5%). The Hepatitis Policy Index (HPI) for the countries with the heaviest hepatitis burden globally from 2019 to 2023 shows that while China has a relatively high starting point, there is still considerable room for improvement.
2. Low Awareness Rate of HBV Infection with Gender, Age, and Regional Disparities
In a 2020 hepatitis B epidemiological survey in China, the overall self-awareness rate of HBsAg-positive individuals aged 15 to 69 was only 41.3%, with men having a lower awareness rate than women. The awareness rate was lower among those aged 60 to 69 than in other age groups, lower in rural areas than in urban areas, and lower in regions with a per capita GDP of less than 54,000 yuan compared to those with a GDP of 54,000 yuan or more.
3. Low Treatment Rate
WHO’s 2022 statistics on hepatitis B testing and treatment coverage in various regions show that China’s HBV infection diagnosis rate is 24.0%, with a treatment rate of only 6.4%. A mathematical modeling study indicates that, under current prevention and treatment strategies, the HBV disease burden will be challenging to reduce in the short term. By 2050, 42.09 million to 45.42 million adults will have hepatitis B, and cumulative deaths from hepatitis B-related causes will reach 11.04 million to 14.36 million between 2022 and 2050. If China delays achieving WHO targets, it will result in severe health and economic burdens. Each year of delay in reaching the goal of 80% treatment by 2030 will result in an additional $55 billion in costs and 334,000 excess deaths.
Urgent Actions Needed to Eliminate Hepatitis B in China
1. Launch Nationwide HBV Screening
A 2022 cost-effectiveness model analysis of nationwide HBV screening in China found that launching nationwide hepatitis B screening (i.e., HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc testing for people aged 18 to 70) in 2021, 2026, or 2031 would effectively increase screening, diagnosis, and treatment rates compared to the status quo. Nationwide hepatitis B screening at different start years would reduce hepatitis B-related deaths. In terms of cost-effectiveness, compared to the status quo, nationwide screening in 2021, 2026, or 2031 would be the most cost-effective, with the screening strategy for people aged 18 to 70 being the most cost-effective.
2. Implement a Universal Treatment Strategy for HBsAg-Positive Individuals
A model study by Dr. Fuqiang Cui’s team shows that a universal treatment strategy for HBsAg-positive individuals has the highest cost-effectiveness.
3. Expand Screening and Adult Vaccination Coverage
The “Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2022 Edition)” propose expanding screening to the general population, recommending HBsAg screening for everyone. Highly sensitive HBV DNA testing methods with a broad linear detection range (quantification limit of 10 to 20 IU/mL) should be used as much as possible. Additionally, the recently released 2024 expert recommendations from the Chinese Preventive Medicine Association on “Screening, Testing, and Management of Adult HBV Infection” and “Adult Hepatitis B Vaccination” both suggest screening for HBsAg, anti-HBs, and anti-HBc in a broad population and recommend adult hepatitis B vaccination.
4. Regular Monitoring for HCC
Global overall survival rates for HCC vary widely, with long-term survival rates for HCC patients in China being relatively low. The best clinical outcomes for HCC patients have been observed in Taiwan and Japan, primarily due to their extensive comprehensive monitoring programs, which allow for the early detection of many HCC cases. In contrast, more patients in other East Asian countries are diagnosed at a late stage, resulting in lower survival rates.
Regular monitoring is key to early detection, treatment, and improved survival rates for HCC patients. A multi-center prospective study in China, conducted between 2017 and 2021, used ultrasound and serum alpha-fetoprotein (AFP) to screen 14,426 HBsAg-positive individuals annually for HCC. After four rounds of screening and follow-up, the mortality risk among HCC patients detected through screening was significantly lower than that of patients clinically diagnosed without screening. Multivariate analysis showed that HCC screening was associated with improved survival rates.
Outlook and Recommendations
Looking ahead, a series of proactive measures must be taken to enhance the effectiveness of prevention and control efforts in the field of chronic hepatitis B.
First, hepatitis B testing should be widely promoted, ensuring active hepatitis B screening in health check-ups not related to school admission, employment, and various medical activities.
Second, a robust referral system for hepatitis B within medical institutions should be established and improved, ensuring that individuals who test positive for hepatitis B can promptly receive professional diagnosis and treatment recommendations from infectious disease or hepatology departments. At the same time, these departments should take on the responsibility of promptly diagnosing and standardizing treatment for hepatitis B patients to improve treatment outcomes.
Additionally, information technology should be used to strengthen reminders for both medical staff and patients regarding HCC monitoring, ensuring AFP and ultrasound testing at least once every six months to achieve early detection, diagnosis, and treatment of HCC. Health administrative departments and disease control agencies should also use information technology to monitor, evaluate, and assess the rates of hepatitis B testing, standardized treatment, and long-term follow-up in medical institutions to ensure the effective implementation of prevention and control measures.
Finally, innovative community-based models for comprehensive hepatitis B testing, referral, standardized treatment, and monitoring should be actively explored and promoted, aiming to build a more complete and efficient hepatitis B prevention and control system that safeguards the health of the public.
