Hepatitis B virus (HBV) infection remains a major public health challenge worldwide. China bears the world’s highest HBV burden, with one-third of the global infected population [
1]. In China, remarkable progress has been made in HBV prevention and control, particularly among infants and children [
2,
3]. However, HBV remains highly prevalent among adults, with an estimated prevalence of 7% between 2013 and 2017 [
4]. A detailed seroepidemiological profile of HBV infection in apparently healthy adults, who constitute the backbone of national workforce, is still lacking. To address this gap, this study based on a nationwide check-up population in China, aimed to provide a comprehensive analysis of the prevalence and incidence rate of HBV infection in apparently healthy Chinese adults.
Our study sample included participants who undergo testing for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) at the Meinian health checkup centers between January 1, 2017, and December 31, 2024. Participants who attended Meinian check-up were apparently healthy males and females seeking preventive healthcare services. Each participant received laboratory tests, physical examinations, and imaging examinations at the centers. HBsAg and anti-HBc testing was performed using ELISA kits. In our cross-sectional analysis of the prevalence of HBV infection, HBsAg positivity indicated current HBV infection, and anti-HBc positivity indicated previous or current HBV infection. In the longitudinal analysis of the incidence rate of HBV infection, analysis was restricted to participants who underwent HBsAg and anti-HBc testing at least twice and had negative results for both markers at baseline (the first visit). An incident HBV infection was defined as HBsAg seroconversion during the follow-up. Finally, 17,924,297 and 3,290,868 adults from 274 cities across all 31 provinces of mainland China were included in the cross-sectional and longitudinal analyses, respectively (
Supplementary Figs. 1,
2). This study was approved by the Institutional Review Board of Peking University (IRB00001052-19077). Informed consents were obtained from study participants.
We assigned weight coefficients to each participant to align the age, sex, and provincial distribution of the study population with the 2020 Chinese national census. Weighted prevalence and corresponding 95% confidence intervals (CIs) were estimated using the Taylor series linearization method. Weighted incidence rates (IRs) were calculated and expressed as per 100,000 person-years, with 95% CIs estimated using Poisson distribution. To investigate risk factors of HBsAg seroconversion, weighted incidence rate ratios (IRRs) and the corresponding 95% CIs were estimated using Poisson weighted regression models. Detailed methodologies are shown in the
Supplementary Method.
Characteristics of the study participants are presented in
Supplementary Table 1 and
2. The prevalence (95% CI) of current HBV infection was 5.34% (5.11–5.57%), with males significantly higher than females (5.98% vs. 4.69%,
P<0.001) (
Fig. 1A). The highest prevalence was observed in the 40–49 years group (
Fig. 1B). Prevalence showed a progressive decline across birth cohorts, from a peak in those born before 1992 to the lowest level in those born after 2002 (
Fig. 1C). Among women of childbearing age, the prevalence of current infection was 4.30% (
Fig. 1J). Geographically, southern region demonstrated more than twice the prevalence of northern region (
P<0.001) (
Fig. 1J). Province-level prevalence also varied significantly (
Supplementary Fig. 3A). Compared to healthy counterparts, the prevalence significantly increased in adults with hepatic abnormalities, including elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBil), alpha fetoprotein (AFP), Fibrosis-4, APRI, and decreased platelet count and albumin (all
P<0.001), while the prevalence significantly decreased in adults with fatty liver disease (
P<0.001) (
Fig. 1J). The prevalence (95% CI) of previous or current HBV infection was 16.63% (15.61–17.65%). Detailed results of the prevalence of previous or current HBV infection are presented in Figure 1D–1F, 1J, and
Supplementary Figure 3B.
During a median follow-up of 2.0 years (interquartile range: 1.1–3.3), the IR (95% CI) of HBsAg seroconversion was 50.41 (48.82–52.03) per 100,000 person-years, with males significantly higher than females (
Fig. 1G and
Supplementary Fig. 4). In overall adults, the IR increased with age and reached its peak at 40–49 years (
Fig. 1H). Those born before 1992 had an IR more than double that of those born after 1992 (
Fig. 1I and
Supplementary Fig. 4). IR was significantly higher in southern than in northern region (
Supplementary Figs. 3C,
4). Compared to adults living in regions with high GDP per capita or high urbanization rate, the IRs in those living in socioeconomically disadvantaged regions were significantly higher (
Supplementary Fig. 4). Moreover, diabetes and impaired kidney function were identified as significant risk factors for HBsAg seroconversion, with the IRRs (95% CIs) estimated to be 1.33 (1.16– 1.53) and 1.70 (1.37–2.11), respectively (
Supplementary Fig. 4).
The global prevalence of current HBV infection was estimated to be 3.2% in 2022, with China’s prevalence at 5.6% in whole population [
5]. The China 2020 national seroepidemiological survey reported a prevalence of 6.11% for current HBV infection among individuals aged 15–69 years [
2]. Our observed prevalence of 5.34% among apparently healthy adults was slightly lower than the national figure. This difference may be attributed to our inclusion of older age groups with a known lower HBV prevalence, the relatively better health status of check-up population compared to the general survey population, and temporal variations between the study periods. The 5.34% prevalence of current infection suggests HBV remains higher-intermediately endemic (5–7.99%) among apparently healthy Chinese adults [
6]. Despite being apparently healthy, this group still exhibited a substantial prevalence of current infection. Furthermore, the 16.63% prevalence of previous or current in-fection found in this population highlights the substantial burden of past infections. Collectively, our findings emphasize the urgent need for universal HBV screening in apparently healthy Chinese adults [
7-
9]. HBV prevention efforts should extend beyond traditional high-risk groups to recognize apparently healthy adults as an important population for screening and case detection.
Consistent with previous studies [
10,
11], HBV infection was more prevalent in southern compared to northern region. Southern provinces such as Fujian, Jiangxi, Guangxi, Hainan, Tibet, and Guangdong had the highest prevalence of current infection (over 8.50%), with Guangxi and Hainan also showing the highest IRs (over 100 per 100,000 person-years). These findings underscore the need for enhanced and prioritized universal HBV screening and focused HBV prevention and control strategies in southern region and highly endemic provinces.
We found a significantly higher prevalence of HBV infection among adults with abnormal liver function, liver fibrosis or cirrhosis, and suspected liver cancer (using elevated AFP as a surrogate marker), suggesting that enhancing HBV screening among these populations could improve case detection. Routine health check-ups provide a unique and practical platform for universal HBV screening [
7], as they enable cost-effective HBV screening and early identification of infected and susceptible individuals.
To the best of our knowledge, this study is one of the first to report the IR of HBV infection among apparently healthy Chinese adults, which was 50.41 per 100,000 personyears. Globally, the estimated IR of chronic hepatitis B was 19 per 100,000 person-years in 2015 and was expected to decrease to 11 per 100,000 person-years by 2030 [
5]. Our estimate was several times this global figure, indicating HBV transmission continued to pose a major threat among apparently healthy Chinese adults. Enhanced preventive measures are of urgent need to control HBV spread.
To combat HBV, China initiated universal hepatitis B vaccination program among infants in 1992 and has provided it free of charge since 2002 [
3]. Our study found that the prevalence and IR of HBV infection among adults born before 1992 or between 1992 and 2002 were several to dozens of times greater than those born after 2002. These findings suggest universal HBV screening and adult vaccination should prioritize individuals born before 1992, who missed the birth dose of the HBV vaccine. We found those aged 40–49 years had the highest prevalence of current HBV infection. This same birth cohort consistently showed the highest prevalence across all previous national surveys [
2,
10,
12].
Compared to healthy counterparts, our analysis demonstrated individuals with diabetes and impaired kidney function had a 33% and 70% higher risk of developing HBV infection, respectively. These elevated risks can be largely attributed to iatrogenic exposure during medical procedures and their compromised immune systems [
13,
14]. Furthermore, male sex, born before the initiation of the universal infant vaccination program, and living in southern or disadvantage regions were identified as risk factors of incident HBV infection. These groups should be prioritized for expanded vaccination campaigns and targeted HBV prevention and control initiatives to effectively reduce new infections.
A limitation of this study was that the check-up database did not include HBV DNA data, preventing the identification of occult infections and potentially underestimating the true prevalence and IR of HBV infection.
In conclusion, among apparently healthy Chinese adults, HBV infection remains higher-intermediately prevalent, with substantial historical infection burden. The IR of HBV infection was several times higher than the global average, indicating a continued risk of transmission. Accelerating progress toward the 2030 HBV elimination goal requires the urgent implementation of universal HBV screening, expand adult vaccination, and targeted public health measures that prioritize high-risk groups to curb HBV further transmission in China.
FOOTNOTES
-
Authors’ contributions
SM, BW, LL, and GL were involved in the conceptualization of this study. SM conducted the statistical analysis and wrote the first draft. ZY, JD, JL, GL, BW, and LL reviewed and edited the manuscript. BW, GL, and LL ensured the resources related to this study.
-
Acknowledgements
This work was funded by the National Natural Science Foundation of China (grant number 82388102, 82192904, 82192900); the National Key Research and Development Program of China (grant number 2023YFC2308703); and the Postdoctoral Fellowship Program of the China Postdoctoral Science Foundation (grant number: GZC20240066).
-
Conflicts of Interest
The authors have no conflicts to disclose.
SUPPLEMENTARY MATERIAL
Supplementary material is available at Clinical and Molecular Hepatology website (
http://www.e-cmh.org).
Supplementary Figure 1.
Flowchart of the study participants. HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; anti-HBc, hepatitis B core antibody.
Supplementary Figure 2.
Distribution of the check-up centers included in the study. (A) Distribution of the check-up centers included in the cross-sectional analysis of the prevalence of HBV infection. (B) Distribution of the check-up centers included in the longitudinal analysis of the incidence rate of HBsAg seroconversion. Each point in the figure represents the location of a check-up center. HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen.
Supplementary Figure 3.
Geographic disparities of the prevalence of HBV infection, and the incidence rate of HBsAg seroconversion in apparently healthy Chinese adults. (A) Geographic disparity of the prevalence of current HBV infection. (B) Geographic disparity of the prevalence of previous or current HBV infection. (C) Geographic disparity of the incidence rate of HBsAg seroconversion. HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen.
Supplementary Figure 4.
Incidence rate and risk factors of HBsAg seroconversion in apparently healthy Chinese adults. Percentages may not add to 100% because of rounding. †IRs and the corresponding 95% CIs were computed based on the exact distribution of weighted sum of Poisson counts. Specifically, we multiplied both the number of seroconversion events and number of person-years with its corresponding weight. The weighted numbers of events and weighted number of person-years were then summed up separately. The weighted IRs were estimated as the weighted sum of events divided by the weighted sum of person-years, multiplied by 100,000. ‡827,122 females were of peak fertility age group (20–39 years), accounting for 59.9% of the overall female adults. ¶The proportion of missing values exceeded 30%. HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; IR, incidence rate; IRR, incidence rate ratio; CI, confidence interval; GDP, gross domestic product; WHO, World Health Organization; eGFR, estimated glomerular filtration rate.
Supplementary Table 2.
Baseline characteristics of the study participants included in the longitudinal analysis of the incidence rate of HBsAg seroconversion
Figure 1.Prevalence and incidence rate of HBV infection in apparently healthy Chinese adults. (A) Overall and sex-specific prevalence of current HBV infection. (B) Age-specific prevalence of current HBV infection. (C) Prevalence of current HBV infection in different birth cohorts. (D) Overall and sex-specific prevalence of previous or current HBV infection. (E) Age-specific prevalence of previous or current HBV infection. (F) Prevalence of previous or current HBV infection in different birth cohorts. (G) Overall and sex-specific incidence rate of HBsAg seroconversion. (H) Age-specific incidence rate of HBsAg seroconversion. (I) Incidence rate of HBsAg seroconversion in different birth cohorts. (J) Prevalence of current HBV infection, and previous or current HBV infection in various subpopulations. HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; TBil, total bilirubin; Alb, albumin; AFP, alpha fetoprotein; APRI, aspartate aminotransferase to platelet ratio index. *P for difference <0.05. **P for difference <0.01. ***P for difference <0.001. †The proportions of missing values exceeded 30%. ‡Linear trend test was performed across subgroups using Cochran-Armitage trend test, which showed P for trend <0.001.
Abbreviations
hepatitis B core antibody
aspartate aminotransferase to platelet ratio index
aspartate aminotransferase
estimated glomerular filtration rate
hepatitis B surface antigen
World Health Organization
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