Seroprevalence of Hepatitis B among the General Population in Shandong Province, Eastern China, an Update 30 Years after the Implementation of the Neonatal Vaccination Program

doi:10.21203/rs.3.rs-4985624/v1

Download PDF

Research Article

Seroprevalence of Hepatitis B among the General Population in Shandong Province, Eastern China, an Update 30 Years after the Implementation of the Neonatal Vaccination Program

https://doi.org/10.21203/rs.3.rs-4985624/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background

In 1992, Hepatitis B vaccine was first recommended for routine neonatal immunization in China. This study aimed to estimate the prevalence of hepatitis B virus (HBV) infection in Shandong Province, eastern China (updating our previous study in 2014), and to help guide the efforts of hepatitis B elimination.

Methods

A total of 5,000 serum samples were obtained from individuals all-aged over 1 year residing in Shandong Province, as part of a seroepidemiological survey of anti-SARS-CoV-2 antibodies conducted in 2023. The chemiluminescence microparticle immunoassay was used to detect serological markers of HBV.

Results

The overall prevalence of HBsAg, anti-HBs and anti-HBc in the 2023 survey was 2.25% (95%CI:1.64–2.87), 46.21% (95%CI:44.05–48.38), and 25.17% (95%CI:23.46–26.88), respectively. The HBsAg prevalence has dropped to 0.28% among individuals younger than 30 years, particularly with less than 0.1% among children aged 1–14 (considerably below the 8% prevalence recorded in 1992). The peak prevalence of HBsAg was observed in individuals aged 40–49 years (5.63%), followed by those aged 30–39 (3.11%).

Conclusion

The Shandong Province has achieved a substantial success in controlling HBV infection among the younger generation. More attention should be paid to HBV-susceptible adults and chronic HBV-infected individuals in order to accelerate progress towards the goal of eliminating hepatitis B in the province.

hepatitis B

sero-epidemiology

prevalence

elimination

Hepatitis B virus (HBV) infection remains a major global public health concern. A recent model estimation revealed that approximately 257.5 million individuals worldwide were infected with HBV in 2022, with a global all-age prevalence of chronic HBV infection estimated at 3.2% [1]. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated that HBV-related diseases resulted in 555 000 global deaths in 2019, accounting for 7.2% of all deaths per 100 000 people worldwide. The global prevalence of HBV infection in the general population varies considerably. According to HBsAg prevalence, countries can be roughly classified into high (≥ 8%), intermediate (2–7%) and low (< 2%) prevalence areas [2].

China used to be an area of high endemicity for hepatitis B infection in the pre-vaccination period. A national serosurvey conducted in 1992 revealed a 9.75% prevalence of hepatitis B surface antigen (HBsAg) in the general population aged 1–59 years[3]. Over the past three decades, the Chinese government has placed a significant emphasis on the timely vaccination of newborns and infants as a key strategy in the battle against hepatitis B. Hepatitis B vaccine (HepB) was first recommended for routine neonatal immunization in 1992, and was subsequently incorporated into the National Expanded Program of Immunization in 2002, with HepB provided free of charge [4–6]. During 2009–2011, a national catch-up campaign was initiated for children under the age of 15 years. In 2011, China implemented the national program for integrating prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV), syphilis and hepatitis B, providing free hepatitis B immunoglobulin (HBIG) for children born to HBV-infected women, and it was then expanded nationwide starting in 2015[7, 8]. Additionally, the dose of HepB has been increased from 5 µg/0.5 mL to 10 µg/0.5 mL since 2011 in order to improve the efficacy of the program. As indicated by data from national sero-epidemiological surveys, the prevalence of HBsAg among the mainland Chinese population aged 1–29 years had declined from 10.1% in 1992 to 2.6% in 2014[9]. Currently, it is estimated that there are approximately 70 million HBsAg-positive individuals in China as of 2022[1].

Shandong Province is situated within the eastern region of China, with an area of 156 700 km² and a population of over 100 million (2020 census data). The data from the Shandong Center for Disease Control and Prevention (CDC) indicated that the provincial coverage of three doses of HepB for infants had exceeded 96% since 2002, as had the high coverage of timely birth-dose HepB (> 96% since 2004), and the coverage of HBIG for infants born to HBsAg-positive mothers (> 92% since 2011). A review of the results from earlier provincial surveys indicates that the HBsAg prevalence among children and adolescents aged 1–14 years had declined from 8% in 1992 to 0.21% in 2014 [10–12].

In 2016, the World Health Assembly set a target of eliminating viral hepatitis as a public health threat by 2030 [13]. In August 2023, the Health Commission of Shandong Province released the Three-Year Action Plan for Accelerating the Elimination of Hepatitis B Hazards in Shandong Province (2023–2025). Knowledge of a population-based sero-epidemiologic survey in an area is crucial for shaping effective preventive and control strategies for hepatitis B. The aim of this study was to provide the latest baseline data on the prevalence of HBV infection (updating our previously published data from 2014), to characterize the change in HBV epidemiology over the past decade, and to help guide the efforts of hepatitis B elimination in the province.

Study population and sampling method

We used the remaining 5000 specimens after testing from the 2023 serosurvey of anti-SARS-Cov-2 antibodies among individuals all-aged over 1 year in Shandong Province. The survey employed a stratified three-stage random sampling method of the national guidelines, with 10 counties in the province selected for inclusion. Subsequently, 20 villages were identified (two per county) through simple random sampling in Shandong Province. Figure 1 depicts the location of the 10 counties sampled. Furthermore, the proportion of sampled residents aged 1–2, 3–17, 18–59, and ≥ 60 years was consistent with the local natural population size. The demographic composition of the 10 sampling locations was found to be similar to that of the province as a whole (Table 1). All study participants provided informed consent. The 2023 COVID-19 sero-epidemiological investigation was uniformly organized at the national level and approved by the China CDC Ethics Committee. The remaining samples from the survey were tested for serologic indicators of hepatitis B, after which an analysis of the data conducted. This study was approved by the Shandong CDC Ethics Committee (SDJK-2023-012-01).

Table 1

Demographic composition of the population in the ten sampled locations and the whole of Shandong Province in China, 2023
Variable	Sampled locations (%)	Whole province(%)^a
age(year)
1–4	6.09	6.42
5–9	6.42	6.35
10–14	6.04	6.00
15–19	5.66	5.02
20–24	5.39	4.53
25–29	4.67	4.41
30–34	9.04	9.00
35–39	6.90	6.79
40–44	6.19	6.27
45–49	7.35	7.66
50–54	8.75	9.01
55–59	7.48	7.65
60–64	5.56	5.77
65–69	5.71	5.97
70–74	3.70	3.97
75–79	2.32	2.40
≥ 80	2.73	2.79
Chi-square = 0.35, P > 0.05
Gender
Male	51.03	50.66
Female	48.97	49.34
Chi-square = 0.01, P > 0.05
^a Data source: Tabulation of the 2020 population census of Shandong province, China

Laboratory testing

With the exception of only one insufficient remaining volume of serum, 4999 (99.98%) frozen separated serum samples were eligible for the test of hepatitis B. The detection indexes included HBsAg, anti-HBs, and anti-HBc, which were determined using chemiluminescence microparticle immunoassay (CMIA) on an automated ARCHITECT-i2000SR analyzer (Abbott reagent, Wiesbaden, Germany). The following signal-to-noise ratios were considered to indicate positivity: HBsAg ≥ 0.05 IU/mL, anti-HBs ≥ 10 mIU/mL, and anti-HBc levels ≥ 1 signal-to-cut-off (S/CO).

Statistical analysis

Considering differential probabilities of selection and the complex sampling designs, we used the SAS 9.4 procedure software to calculate point estimates and 95% confidence intervals (CIs) of HBsAg, anti-HBs, and anti-HBc prevalence through the use of weighting adjustments. The demographic adjustment was based on the 2020 permanent population data of Shandong Province [14]. The Taylor series linearization method was used for the estimation of variance. The 95% CIs for the prevalence of HBsAg, anti-HBs, and anti-HBc were compared. Any CIs that did not overlap were considered as statistically significant. The ten investigation counties were divided into three geographic areas. The eastern area included Huangdao, Laishan, Qingzhou, and Rongcheng, the middle area included Shizhong, Linzi, and Lanling, and the western area included Liangshan, Yucheng, and Mudan. The urban area included Shizhong, Huangdao, Laishan, Linzi, and Mudan, while the rural area included Qingzhou, Liangshan, Rocheng, Lanling, and Yucheng.

Demographic Characteristics

In total, 4999 samples were analyzed in the 2023 survey. The mean age of the participants was 46 ± 22 years, with a male-to-female ratio of 0.82:1. A total of 1999 participants (39.99%) resided in urban areas and 3000 (60.01%) in rural areas. The proportion of participants living in the eastern, central and western region of Shandong Province was 39.98%, 30.01% and 30.01%, respectively, and the proportion of participants by age group is shown in Table 2.

Table 2

Distribution of HBV serological markers by age in in Shandong Province, 2023
Age group(Years)	Total		HBsAg		Anti-HBs		Anti-HBc
Age group(Years)	No.	Proportion(%)	Seroprevalence(%)	95%CI	Seroprevalence(%)	95%CI	Seroprevalence(%)	95%CI
1–4	106	2.12	0.00	0.00–0.00	78.57	70.93–87.90	7.87	2.65–13.09
5–9	290	5.80	0.00	0.00–0.00	59.38	51.72–67.03	5.20	2.44–7.97
10–14	364	7.28	0.09	0.00-0.27	36.50	29.27–43.93	1.52	0.50–2.54
15–19	138	2.76	0.00	0.00–0.00	38.53	20.65–50.88	6.75	2.18–11.31
20–29	279	5.58	0.97	0.00-2.14	51.11	45.00-57.23	5.06	2.83–7.30
30–39	564	11.28	3.11	1.35–4.87	59.82	48.31–71.33	23.07	17.39–28.75
40–49	668	13.36	5.63	3.03–8.24	42.78	38.03–47.53	31.48	26.89–36.06
50–59	1148	22.96	2.63	1.42–3.83	38.80	33.44–44.16	36.87	32.86–40.88
60–69	754	15.08	2.73	1.40–4.07	34.63	27.62–41.65	38.74	30.63–46.84
≥ 70	688	13.76	1.32	0.14–2.50	36.14	32.88–39.41	48.21	40.69–55.74
Total	4999	100.00	2.25	1.64–2.87	46.21	44.05–48.38	25.17	23.46–26.88

Prevalence of HBV serological markers in 2023

Overall. the weighted prevalences of HBsAg, anti-HBs, and anti-HBc among the entire population surveyed in 2023 were 2.25% (95%CI:1.64–2.87), 46.21% (95%CI:44.05–48.38), and 25.17% (95%CI:23.46–26.88), respectively. Among the 1,177 individuals aged 1–29 years, only 5 (0.28%) were detected positive for HBsAg. Notably, none of the children aged 1–9 years were detected. The individuals who tested positive for HBsAg were predominantly distributed among those aged 30 years and older. The peak prevalence of HBsAg was observed in individuals aged 40–49 years (5.63%) and 30–39 years (3.11%). Similarly to that of HBsAg, anti-HBc positivity was predominantly present in individuals aged ≥ 30 years compared to those aged 1–29 years (p < 0.05). Furthermore, the prevalence of anti-HBc exhibited a gradual increasing trend with age in those of aged 30 years and older (Table 2). The prevalence of anti-HBs was highest in children aged 1–4 years (78.57%) and then decreased to 36.50% and 38.53% in children aged 10–14 and 15–19 years, respectively. Subsequently, there was a slight increase in the prevalence of anti-HBs in the age groups of 20–29 and 30–39 years (51.11% and 59.82%, respectively), which then declined with increasing age.

The prevalence of HBsAg, anti-HBs, and anti-HBc was comparable between males and females. The prevalence of HBsAg was found to be slightly lower in urban areas compared to that of rural areas. In contrast, the prevalence of anti-HBs was slightly higher in urban areas. However, these differences were not statistically significant (all p > 0.05). A higher prevalence of anti-HBc was observed in urban areas than in rural areas (p < 0.05). The prevalence of HBsAg among individuals residing in the western regions of Shandong was found to be higher than that observed in the eastern and central regions, but with no statistically significant difference observed (all p > 0.05). The highest prevalence of HBsAg was identified in public service workers (3.85%), followed by workers (3.53%) and farmers (3.46%), while the lowest prevalence was observed among students (0.03%) (Table 3).

Table 3

Prevalence of HBV serological markers by gender,occupation, and residential area in Shandong Province, 2023
	Sample tested	HBsAg (% (95% CI))	Anti-HBs (% (95% CI))	Anti-HBc (% (95% CI))
Gender
Male	2259	2.43 (1.49–3.37)	45.72 (42.50-48.93)	25.15 (22.64–27.66)
Female	2740	2.07 (1.28–2.86)	46.72 (43.83–49.62)	25.19 (22.89–27.49)
Occupation
Farmer	2227	3.46 (2.25–4.66)	35.92 (33.26–38.58)	36.38 (33.73–39.04)
Worker	447	3.53 (0.96–6.10)	51.18 (44.26–58.10)	24.55 (18.55–30.55)
Cadre	267	2.47 (0.18–4.76)	55.59 (46.88–64.31)	24.52 (18.06–30.98)
Student	704	0.03 (0.00-0.10)	45.36 (40.06–50.66)	4.98 (2.92–7.04)
Medical staff	95	2.30 (0.00-6.44)	76.19 (65.34–87.04)	17.54 (7.53–27.55)
Public service worker	164	3.85 (0.00-7.91)	42.26 (31.00-53.52)	19.99 (11.98–28.01)
Retiree	271	1.64 (0.00-3.82)	39.29 (31.45–47.13)	43.29 (35.23–51.35)
Household and unemployed personnel	417	1.87 (0.53–3.20)	42.64 (34.69–50.59)	34.41 (27.17–41.65)
Others	209	1.89 (0.09–3.68)	51.66 (38.81–64.51)	28.03 (21.70-34.36)
Residential area
Urban	2499	2.04 (1.42–2.66)	50.44 (44.97–55.87)	27.38 (25.06–29.72)
Rural	2500	2.38 (1.88–2.88)	43.62 (37.84–49.40)	23.81 (22.74–24.89)
Geographic location
Eastern Shandong	1999	2.17 (1.63–2.72)	45.30 (39.24–51.35)	25.32 (23.72–26.91)
Central Shandong	1500	1.88 (0.96–2.81)	50.01 (43.75–56.28)	24.92 (21.05–28.78)
Western Shandong	1500	3.00 (2.02–3.97)	43.96 (41.55–46.37)	25.05 (22.69–27.42)

Comparison of HBV serologic markers prevalence in 2006, 2014, and 2023

We compared the findings of 2023 survey with those from previous surveys conducted in 2006 and 2014 (both covering individuals aged 1–59 years). The HBsAg prevalence among children aged 1–14 years declined by 85% during 2006–2014 (from 1.36–0.21%) and 86% during 2014–2023 (from 0.21–0.03%). Meanwhile, a moderate decline (from 3.81–2.96%) was observed among individuals aged 15–59 years during 2006–2023. The prevalence of anti-HBs increased by 9% (from 72.14–78.57%) among children aged 1–4 years and by 17% (from 40.04–46.88%) among individuals aged 15–59 years during 2006–2023. The prevalence of anti-HBs in urban and rural populations, as well as in different regional populations, remained relatively stable across all three surveys. The anti-HBc prevalence among individuals aged 5–14 and 15–59 years in the 2023 survey was found to be lower than that recorded in 2006. Conversely, there was an increase among children aged 1–4 years (Fig. 2).

The findings of the four sero-epidemiological surveys conducted among the community population of Shandong Province revealed a decline in the prevalence of HBsAg, from 6.40% in 1992 (1–59 years)[12], to 3.39% in 2006 (1–59 years)[10], to 2.49% in 2014 (1–59 years)[10], and to 2.25% (the entire population aged over 1 year) in 2023. Our findings highlight the fact that the province remains an area of intermediate endemicity of HBV infection, yet it is undergoing a gradual transition towards a low-prevalence status (< 2%). In comparison to the prevalence of HBsAg among individuals younger than 30 years in the pre-vaccine era of 1992, the 2023 survey revealed a marked reduction in this metric, falling to a prevalence of only 0.28%. Of note, the prevalence among children aged 1–14 years had declined from 8% in 1992, to 1.36% in 2006, to 0.21% in 2014, and further to less than 0.1% in 2023. If the province is taken as a unit, this represents a great advance towards the WHO’s goal of eliminating viral hepatitis as a public health threat by 2030. A model estimation indicates that the HBsAg positivity rate among children aged < 5 years in China is anticipated to fall below 0.1% by 2025[15]. The observed decline in HBsAg prevalence should be attributed primarily to the beneficial impact of universal childhood vaccination policies begining in 1992 and had covered all the population under 30 years of age by 2023. Additionally, the program for integrating the prevention of MTCT of HIV, syphilis, and HBV has had a positive impact since 2011, which provided HBsAg screening for pregnant women and free HBIG for infants born to all HBsAg-positive mothers. The Chinese government plans to achieve the goal of eliminating MTCT of the three diseases by 2025, with one of the aims of reducing the rate of HBV transmission to less than 1%. A national evaluation and validation of the Shandong Province's elimination program is scheduled to be completed in the second half of 2024.

In the 2023 survey, the higher prevalence of HBsAg was present in individuals aged ≥ 30 years, similar to the results of other seroepideniology studies conducted in China[16, 17]. Subsequent analysis indicated that the peak prevalence of HBsAg was seen in the population aged 30–49 years, consistent with the results of the 2020 survey in Beijing[18]. With the improvement of routine hepatitis B immunization, the shift in the age of HBV infection, and the improvement of socio-economic levels, it is becoming increasingly evident that an emphasis on hepatitis B immunization for populations beyond eligible children is is also essential for accelerating hepatitis B elimination. The administration of HepB to healthy adults has been shown to be good at inducing the production of protective antibodies and providing a long-lasting immune memory[19–22]. However, in recent years, only a limited number of pilot areas in Shandong Province have implemented a free HepB policy for certain high-risk adults, whereas the province as a whole still adopts a voluntary, self-paid model of HepB immunization for adults. The deficiencies in this strategy, coupled with other factors, has resulted in suboptimal HepB coverage in the province, especially in rural areas[23]. Thus, HepB immunization for susceptible adults should be intensified so as to reduce the incidence of hepatitis B in adults and the whole population.

Consistent with previous findings[9, 16, 17], the results of our study in 2023 indicated that the prevalence of anti-HBs was highest among children aged 1–4 years, with a subsequent decline in prevalence with increasing age under 20 years of age. Currently, it is generally not recommended to provide booster immunizations for immunologically completent individuals who have received a full primary series due to the presence of immune memory[24, 25]. Nevertheless, a minority of researchers hold the view that the booster immunization should be administered when anti-HBs levels decreased < 10 mU/ml, as this may result in the loss of immune memory and an increased difficulty in stimulating the memory response[26, 27]. Additional studies is needed to offer insights into the optimal vaccination strategies for ensuring durable protection against HBV. In addition, the prevalence of anti-HBs rebounded in the 20–29 and 30–39 age groups in comparison to that observed in the 10–19 age group, and then kept below 43% in subsequent age groups. The observed increase in the 20–29 age group might be primarily attributed to the implementation of a booster dose of HepB to college freshmen with negative or weakly positive serological results[28]. The rise in the 30–39 age group is likely the result of a combination of factors, including vaccination and an increase in natural HBV infection.

As expected, the 2023 survey revealed that the prevalence of anti-HBc was markedly higher in individuals aged ≥ 30 years than in those aged 1–29 years, which was in accordance with the HBsAg findings of this study. Notably, children aged 1–4 years showed a higher prevalence of anti-HBc compared to that in 2006 and 2014. In light of the fact that none of these children had HBsAg positivity, it is speculated that the higher prevalence of anti-HBc might be due to maternal transmission across the placental barrier. This warrants investigation of maternal HBV serologic markers[29]. Also, the relatively small sample size of this age group in the 2023 survey might lead to potential biases in the study. Additionally, it was observed that a greater prevalences of anti-HBc was present in individuals residing in urban areas than in those in rural areas, possibly due to the fact that high-risk behaviors, such as unsafe sexual behavior and intravenous drug use, were more common in urban settings[30].

The study found that the prevalence of HBsAg, anti-HBs, and anti-HBc among different occupational groups in 2023 varied considerably, with relatively high HBsAg prevalence observed in public service workers, farmers, and workers. This finding aligns with results from prior studies conducted in the province and in other regions[10, 18, 31]. The high prevalence in these groups was likely due to a combination of factors, including frequent interpersonal contact, limited knowledge about HBV infection and prevention, and low awareness of proactive HepB vaccination. It is recommended to publicize and popularize the knowledge of hepatitis B for these occupational groups. Concurrently, efforts should be made to elevate the coverage of HepB for them.

As a country with the greatest burden of HBV infection worldwide, China will play a pivotal role in the global eradication of hepatitis B by 2030[32]. However, the current situation is such that there are still large gaps in achieving the goals of reducing HBV mortality and elevating the coverage of diagnosis and treatment[33]. The current high prevalence of HBsAg in older adults represents a substantial risk factor for HBV transmission and chronic complications. Furthermore, the majority of chronic HBV-infected individuals were unaware of their HBV infection status, with a previous study showing that more than 80% of adults with HBV infection was unable to receive treatment due to a lack of awareness about their illness[34]. A delayed diagnosis can result in a delayed detection of cirrhosis, liver failure, and hepatocellular carcinoma due to the asymptomatic nature of these conditions until the onset of end-stage liver disease[35]. Consequently, the implementation of optimal hepatitis B screening and management strategies, along with the early initiation of treatment, will be a critical step towards the goal of eliminating hepatitis B in China.

Some limitations of the study should also be taken into consideration. Firstly, the sampling population for the survey was derived from the serosurvey of anti-SARS-Cov-2 antibodies rather than a standard study design of hepatitis B sero-survery. Moreover, the 10 survey counties selected in 2023 differed from those surveyed in 2006 and 2014 ( both in the same 12 counties)[10, 11]. These discrepancies may weaken the representativeness of the surveyed population in Shandong Province. Secondly, the testing methods used in the 2023 survey differed from those used in 2006 and 2014, potentially resulting in certain observational bias in the prevalence of HBV serological markers. The 2006 and 2014 surveys utilized enzyme-linked immunosorbent assay (ELISA), whereas the 2023 survey used CMIA assay. The CMIA assay represents the pinnacle of technological advancement, offering the benefits of high sensitivity and specificity[36, 37]. Hence, it may be more effective than ELISA methods in in detecting positive serologic indicators of HBV. However, specimens with indeterminate results in the 2006 and 2014 surveys were also reconfirmed through the use of the CMIA assay with Abbott reagent[10]. Consequently, we believe that the detection results of this survey were still sufficiently comparable to those of 2014 and 2016. Lastly, the 2023 survey failed to gather additional detailed information from the study participants, including the history of hepatitis B immunization and other HBV infection risk factors, thus preventing the conduct of a more comprehensive analysis.

In conclusion, our study demonstrated that 30 years after the implementation of the neonatal vaccination program, Shandong Province has achieved a substantial success in controlling the prevalence of HBV infection among young people. However, the prevalence of HBV infection remains relatively high among persons older than 30 years. In order to improve the efficacy of the ongoing efforts to combat hepatitis B, more attention should be paid to the implementation of comprehensive interventions for HBV-susceptible adults and the improvement of screening and standardized treatment rates for chronically HBV-infected individuals. Such actions have the potential to facilitate the province and the country as a whole in achieving the WHO's target of hepatitis B elimination by 2030.

Acknowledgements

We thank all the relevant health workers who took part in the collection of samples from CDCs of Shizhong, Huangdao, Linzi, Laishan, Qingzhou, Liangshan, Rocheng, Lanling, Yucheng and Mudan in the study.

Author Contributions

Li Zhang contributed to study concept. Bingyu Yan, Xiaomeng Zhang contributed to initial drafting of the manuscript. Bingyu Yan, Jngjing Lv, Yi Feng, Xin Meng, Xiaojuan Lin, Yan Zhang, Suting Wang, Feng Ji, Meng Chen, Xinyu Yuan, and Zexin Tao contributed to the collection of data and blood sample. Bingyu Yan and Xiaomeng Zhang contributed to data analyse. Li Zhang contributed to critical review and revision of the article.

Funding

This work was supported by grants from Taishan Scholar Program of Shandong Province, China (No. tstp20221164)

Data availability

Data used and analyzed during this study are provided in full within the present manuscript.

Ethics approval and consent to participate

The survey was approved by the Ethics Committee of the China CDC. A written informed consent was obtained from each individual or guardian (if age <18 years) prior to investigation. The use of the remaining samples to test for serologic indicators of hepatitis B was approved by the Shandong CDC Ethics Committee (SDJK-2023-012-01).

Consent for publication

All participants were consent for the publication of this manuscript.

Competing interests

The authors declare no conflict of interest.

Polaris Observatory Collaborators. Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: a modelling study. Lancet Gastroenterol Hepatol. 2023;8(10):879–907.
Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30(12):2212–9.
Z D. G Q: Virus hepatitis in China: seroepidemiological survey in Chinese population (part one) 1992–1995. Beijing: Beijing Science and Technology Literature; 1996.
Kane MA, Hadler SC, Lee L, Shapiro CN, Cui F, Wang X, Kumar R. The inception, achievements, and implications of the China GAVI Alliance Project on Hepatitis B Immunization. Vaccine. 2013;31(Suppl 9):J15–20.
Liang X, Cui F, Hadler S, Wang X, Luo H, Chen Y, Kane M, Shapiro C, Yang W, Wang Y. Origins, design and implementation of the China GAVI project. Vaccine. 2013;31(Suppl 9):J8–14.
Liang X, Bi S, Yang W, Wang L, Cui G, Cui F, Zhang Y, Liu J, Gong X, Chen Y, et al. Reprint of: Epidemiological serosurvey of Hepatitis B in China–declining HBV prevalence due to Hepatitis B vaccination. Vaccine. 2013;31(Suppl 9):J21–28.
Wang AL, Qiao YP, Wang LH, Fang LW, Wang F, Jin X, Qiu J, Wang XY, Wang Q, Wu JL. Integrated prevention of mother-to-child transmission for human immunodeficiency virus, syphilis and hepatitis B virus in China. Bull World Health Organisation. 2015;93(1):52–6.
Wang X, Wang Q, Wang C, Zhang T, Li Z, Ma Z, Wang A. Prevention of Mother-To-Child Transmission of HIV-China,2011–2020. China CDC Wkly. 2021;3(048):1018–21.
Cui F, Shen L, Li L, Wang H, Wang F, Bi S, Liu J, Zhang G, Wang F, Zheng H, et al. Prevention of Chronic Hepatitis B after 3 Decades of Escalating Vaccination Policy, China. Emerg Infect Dis. 2017;23(5):765–72.
Liu J, Lv J, Yan B, Feng Y, Song L, Xu A, Zhang L, Yan Y. Comparison between two population-based hepatitis B serosurveys with an 8-year interval in Shandong Province, China. Int J Infect diseases: IJID : official publication Int Soc Infect Dis. 2017;61:13–9.
Zhang L, Xu A, Yan B, Song L, Li M, Xiao Z, Xu Q, Li L. A significant reduction in hepatitis B virus infection among the children of Shandong Province, China: the effect of 15 years of universal infant hepatitis B vaccination. Int J Infect diseases: IJID : official publication Int Soc Infect Dis. 2010;14(6):e483–488.
Dai ZQG. Virus hepatitis in China: seroepidemiological survey in Chinese population (part two) 1992–1995. Beijing Science and Technology Literature Press 1996:pp. 110–119.
Organization WH. Global health sector strategy on sexually transmitted infections 2016–2021 toward ending STIs [internet]. WHO; 2016 [cited 2023 Feb 22] Available from: https://wwwwhoint/teams/global-hiv-hepatitis-and-stis-programmes/strat 2016.
Shandong Provincial Bureau of Statistics, Office of the Leading Group of Shandong Province for the Seventh National Populaton Census. SHANDONG POPULATION CENSUS YEARBOOK 2020: China Statistics Press; 2022.
Hui Z, Nayagam S, Chan P, Fuzhen W, Thursz M, Zundong Y, Ning M, Xiaojin S, Cui F, Guomin Z, et al. Progress towards elimination of mother-to-child transmission of hepatitis B virus infection in China: a modelling analysis. Bull World Health Organ. 2021;99(1):10–8.
Gao P, Wang H, Chen WX, Sun YN, Zhang W, Pang XH, He X, Wu J. A sero-epidemiological study of hepatitis B among general population in Beijing. Zhonghua Liu Xing Bing Xue Za Zhi. 2016;37(5):658–62.
Zhou Y, Zhao B, Shi W, Ding X, Shen L, Zhou X, He H. The infection rates of HBV and HCV decreased significantly in Zhejiang Province, China: A comparative study based on the data of two sero-epidemiological surveys in 1992 and 2020. J Viral Hepatitis. 2023;30(6):489–96.
Qian Q, Yan L, Qian L, Xiuying L, Wei Z, Zheng Z, Wei Z, Li N, Xinghuo P. A sero-epidemiological survey of hepatitis B virus among the population over 18 year old in Chaoyang District of Beijing, 2020. Zhonghua Liu Xing Bing Xue Za Zhi. 2023;44(2):263–7.
McMahon BJ, Bruden DL, Petersen KM, Bulkow LR, Parkinson AJ, Nainan O, Khristova M, Zanis C, Peters H, Margolis HS. Antibody levels and protection after hepatitis B vaccination: results of a 15-year follow-up. Ann Intern Med. 2005;142(5):333–41.
Bruce MG, Bruden D, Hurlburt D, Zanis C, Thompson G, Rea L, Toomey M, Townshend-Bulson L, Rudolph K, Bulkow L, et al. Antibody Levels and Protection After Hepatitis B Vaccine: Results of a 30-Year Follow-up Study and Response to a Booster Dose. J Infect Dis. 2016;214(1):16–22.
Zhang L, Yan BY, Lyu JJ, Liu JY, Kong Q, Wu WL, Feng Y, Xu AQ. Persistence of immune memory and its related factors at 12 years after hepatitis B vaccination among adults. Zhonghua Yu Fang Yi Xue Za Zhi. 2019;53(5):497–502.
Wu W, Lv J, Liu J, Yan B, Feng Y, Xu A, Zhang L. Persistence of immune memory among adults with normal and high antibody response to primary hepatitis B vaccination: Results from a five-year follow-up study in China. Hum vaccines immunotherapeutics. 2018;14(10):2485–90.
Liu J, Lv J, Yan B. Knowledge, attitude and practice (KAP) about hepatitis B prevention among residents in rural areas. Chin J Public Health. 2013;29(011):1561–4.
WHO. Hepatitis B vaccines: WHO position paper, July 2017 - Recommendations. Vaccine. 2019;37(2):223–5.
Leuridan E, Van Damme P. Hepatitis B and the need for a booster dose. Clin Infect diseases: official publication Infect Dis Soc Am. 2011;53(1):68–75.
Shan AL, Li C, Wu WS, He HY, Liu Y, Liu P, Xie XH. Current status of hepatitis B immunization and strengthened immune memory among first-year middle school students in Tianjin. Zhonghua Yu Fang Yi Xue Za Zhi. 2010;44(6):531–4.
Ren H, Li Y, Wu H, Yu Y. Immunity status of hepatitis B vaccine immunized population and influence factors in anti-HBs declined group. Shanghai J Prev Med. 2010;22:121–3.
Xu Y, Liu Y, Wang J, Che X, Zhang X, Jiang W, Du J, Zhang X, Gu W. Hepatitis B virus infection seromarkers among college freshmen and their immune responses to different vaccination policies of hepatitis B vaccine. Hum vaccines immunotherapeutics. 2021;17(11):4587–94.
Wang JS, Chen H, Zhu QR. Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers. World J Gastroenterol. 2005;11(23):3582–5.
Su S, Wong WC, Ong JJ, Seto WK, Zhang L. The optimal screening strategy for chronic hepatitis B virus infection in China - Authors' reply. Lancet Global health. 2022;10(6):e793.
Liu J, Zhang S, Wang Q, Shen H, Zhang M, Zhang Y, Yan D, Liu M. Seroepidemiology of hepatitis B virus infection in 2 million men aged 21–49 years in rural China: a population-based, cross-sectional study. Lancet Infect Dis. 2016;16(1):80–6.
Wang FS, Fan JG, Zhang Z, Gao B, Wang HY. The global burden of liver disease: the major impact of China. Hepatology (Baltimore MD). 2014;60(6):2099–108.
Liu J, Liang W, Jing W, Liu M. Countdown to 2030: eliminating hepatitis B disease, China. Bull World Health Organ. 2019;97(3):230–8.
Wang C, Cui F. Expanded screening for chronic hepatitis B virus infection in China. Lancet Global health. 2022;10(2):e171–2.
Nguyen MH, Wong G, Gane E, Kao JH, Dusheiko G. Hepatitis B Virus: Advances in Prevention, Diagnosis, and Therapy. Clin Microbiol Rev 2020, 33(2).
Kim H, Oh EJ, Kang MS, Kim SH, Park YJ. Comparison of the Abbott Architect i2000 assay, the Roche Modular Analytics E170 assay, and an immunoradiometric assay for serum hepatitis B virus markers. Ann Clin Lab Sci. 2007;37(3):256–9.
Liaw YF. Clinical utility of hepatitis B surface antigen quantitation in patients with chronic hepatitis B: a review. Hepatology (Baltimore MD). 2011;53(6):2121–9.

No competing interests reported.

Download PDF

Editorial decision: Revision requested
30 Aug, 2024
Editor assigned by journal
28 Aug, 2024
Submission checks completed at journal
28 Aug, 2024
First submitted to journal
27 Aug, 2024

You are reading this latest preprint version

Seroprevalence of Hepatitis B among the General Population in Shandong Province, Eastern China, an Update 30 Years after the Implementation of the Neonatal Vaccination Program

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Introduction

Materials and Methods

Study population and sampling method

Laboratory testing

Statistical analysis

Results

Demographic Characteristics

Prevalence of HBV serological markers in 2023

Comparison of HBV serologic markers prevalence in 2006, 2014, and 2023

Discussion

Declarations

References

Additional Declarations

Status:

Version 1