Objectives Hepatitis B virus (HBV) infection is a global public health threat, and couples of reproductive age comprise a key population in aiming to reduce both the vertical and horizontal transmission of HBV. We aimed to update knowledge on the seroepidemiology status of HBV in Guangdong, China among a large number of couples planning conception, and to identify high-risk subgroups.
Design A cross-sectional study was performed in Guangdong, China from 2014 to 2017.
Setting The data were collected from 641 642 couples (1 283 284 individuals) participating in the National Free Preconception Health Examination Project in Guangdong, China from 1 January 2014 to 31 December 2017. For each participant, sociodemographic data were obtained and a serum sample was tested for HBV infection status.
Results 161 204 individuals (12.56%) were positive for hepatitis B surface antigen (HBsAg+), and 47 318 (3.69%) were positive for both HBsAg and hepatitis B e antigen (HBsAg+ and HBeAg+). There was a higher prevalence of HBsAg+ (12.77% vs 9.42%, p<0.05) and HBsAg+ and HBeAg+ (3.77% vs 2.45%, p<0.05) among the participants with a Guangdong household registration than a non-Guangdong household registration. Similarly, the prevalence of HBsAg (13.26% vs 11.72%, p<0.05) and HBsAg+ and HBeAg+ (4.31% vs 2.94%, p<0.05) was higher among participants not living in the Pearl River Delta than those living in the Pearl River Delta. At the couple level, 12 446 couples (1.94%) were both positive; in 51 849 (8.08%), only the wife was positive; in 84 463 (13.16%), only the husband was positive. Moreover, HBsAg+ prevalence was lowest in couples where both individuals were vaccinated (18.63%) and highest in couples where neither the wife or husband was vaccinated (24.46%).
Conclusion There was a relatively high HBsAg+ prevalence in married couples in this high-epidemic region and urgent prevention strategies are required, such as ensuring access to health services for those not living in the Pearl River Delta, and expanding vaccine programmes to high-risk adults.
- public health
- infection control
Data availability statement
No data are available.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
Hepatitis B surface antigen prevalence has been compared in terms of multiple important sociodemographic data, including household registrations, regions and hepatitis B vaccination status.
This was the first study that involved a large number of couples from both rural and urban areas in a high-epidemic region.
The history of vaccination was self-reported by participants, and direct access to medical records was not available to the researchers.
Hepatitis B virus (HBV) infection is a global public health threat, particularly in developing countries. HBV infection can result in chronic hepatitis and ultimately develop into life-threatening issues such as cirrhosis or liver cancer.1 According to the WHO, about 296 million people were chronically infected with HBV, and an estimated 820 000 deaths were caused by this virus in 2019.1 The frequency of HBV infection is geographically diverse worldwide, and regions could be broadly classified into high (>8% hepatitis B surface antigen (HBsAg) prevalence), higher-intermediate (5%–7.99%), lower-intermediate (2%–4.99%) and low (<2%) prevalence area.2 China is a country that bears a heavy burden of HBV for both its higher intermediate prevalence and its large HBV-infected population.3 4 Recent meta-analyses in China reported a pooled estimated HBV prevalence of 6.89% from 2013 to 2017 and an estimated population of 84 million with positive HBsAg in 2018.2 Efforts are still needed to reduce HBV transmission in this country.
Located in the south of China, Guangdong province has the highest HBV prevalence nationwide, and one community-based study in 2016 showed an HBsAg prevalence of 8.76% in the Pearl River Delta region of Guangdong.5 Specifically, some high-risk subgroups deserved our attention to control HBV infection in this province, such as the population living in areas with low economic development and the large-scale interprovincial migrants. Level of economic development varies across regions in Guangdong and higher development might help ensure better access to healthcare resources. Nearly 30 million labour workers migrated to Guangdong for better employment in 2020 and migrants originating from low or intermediate-epidemic provinces are susceptible to HBV infection in this high-epidemic province.6 Overall, studies regarding hepatitis B and associated risk factors in Guangdong are relatively rare. There were only three provincial surveys in 2002, 2006 and 2013 reporting on HBV epidemiology in Guangdong.7–9 Furthermore, all these above studies in Guangdong focused on the general population or children aged <15 years.
According to a WHO bulletin in 2019, most HBV carriers are infected through vertical transmission from their mothers in high-epidemic areas, suggesting that it is essential to provide treatment for HBV-positive women.10 In addition, when a father is HBV positive, seronegative partners or children can also be infected through the intrafamilial (horizontal) routes.11 Couples trying to conceive may typically be having sex without barrier contraception, bringing additional risks of HBV infection from one partner to the other. As a result, both partners should be involved in prenatal care planning to reduce risks of transmission. As the number of couples planning to have a baby is expected to increase due to the multiple-child policy in China, married couples deserve more attention for HBV prevention, and it is necessary to fully understand the hepatitis B status of this population. However, to the best of our knowledge, current published studies about HBV prevalence among Chinese married couples used a limited sample in one city or merely recruited couples from rural areas.12–14 Moreover, relevant couple-based research in other countries involved a small or medium sample size, counted in hundreds to thousands. There are still few studies examining larger populations from both rural and urban areas in a high-burden HBV region.
Therefore, further research is necessary targeting reproductive-aged couples in Guangdong, which is meaningful for local HBV epidemic control by decreasing both vertical and horizontal transmission. Furthermore, exploration of HBV infection among couples in Guangdong will not only add to the understanding of HBV prevention in developing countries, but also provide insight into global control of HBV among couples in other high-epidemic regions. The aims of the present study were (1) to update the seroepidemiology status of HBV in Guangdong in a large number of married couples, and (2) to identify subgroups of higher HBV prevalence by comparing prevalence across the population of different important sociodemographic data, including household registrations, regions and hepatitis B vaccination history.
Study design and participants
We conducted a cross-sectional study among couples who participated in the National Free Preconception Health Examination Project (NFPHEP) in Guangdong. NFPHEP was a nationwide project launched by the National Health Commission of the People’s Republic of China, aiming to improve pregnancy outcomes. It provided free preconception care and follow-up for married couples who planned to conceive within the next 6 months. The study used convenience sampling and participation was voluntary. Multiple government departments joined with the community to publicise the study among couples planning pregnancy in various ways to ensure the benefits of the project were fully understood. Relevant grassroots personnel introduced the purpose, content and service procedures of the project in key sites, such as the marriage registry office, to keep in touch with as many couples as possible. Eligible couples were then recruited by trained healthcare staff in local maternal and child healthcare service centres. Detailed design and implementation of NFPHEP are reported in prior publications.15 16
This study only used the baseline data of all couples at the preconception stage. Individual information of each participant was collected by healthcare staff through an interviewer-administered questionnaire, including age, gender, education, occupation, household registration, region and history of hepatitis B vaccination. Serum sample of each participant was taken by the staff and sent to locally qualified laboratories. HBsAg, antibody against HBsAg (anti-HBs), hepatitis B e antigen (HBeAg), antibody against HBeAg and antibody against hepatitis B core antigen were tested in all participants using ELISA kits. In this study, those with positive HBsAg in serum were classified as being HBV positive. Furthermore, positivity for both HBsAg and HBeAg represented a high level of infection. Anti-HBs positivity with other HBV markers negative indicated immune response after hepatitis B vaccination. Those with all HBV markers negative were considered susceptible to HBV infection. All data were uploaded to a web-based medical service information system supported by National Research Institute for Family Planning. Quality control and external quality assessment biannually were performed by the Centre of Clinical Laboratories for Quality Inspection and Detection of Guangdong Institute of Family Planning Science and Technology.
The statistical analysis
Percentages and frequency distributions were used to describe the baseline characteristics. The distributions of all HBV markers across different household registration, regions, age and gender were compared using the Χ2 test. The household registration, namely Hukou in Chinese, serves as a legal proof of identity for citizens, recording one’s basic household information and the area where he or she is allowed for permanent residence. People without a local household registration need to apply for legal temporary residence regularly. In this study, the household registration information of each participant was categorised into Guangdong household registration or non-Guangdong household registration. Meanwhile, the region information of each participant was geographically categorised into the Pearl River Delta or non-Pearl River Delta. Generally, the Pearl River Delta, a Chinese mega-metropolitan area, is much wealthier than other areas in this province. The prevalence of all HBV markers and the corresponding 95% CIs were calculated. Statistical significance was defined as p<0.05. All analyses were conducted using SPSS (V.25.0).
Patient and public involvement
Patients or the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research.
From 1 January 2014 to 31 December 2017, 679 197 couples aged 20–49 years with tested serum samples were enrolled by the NFPHEP in Guangdong province using a convenient sampling method that covered over 80% of the target population.15 Among the 679 197 couples, 641 642 couples (1 283 284 individuals) with complete information on HBV vaccination history were included in the final analysis.
The 1 283 284 participants had a median age of 26.00 years (IQR 24.00–30.00) and 955 204 (74.43%) were aged 20–29 years. A total of 1 204 259 (93.84%) had Guangdong household registration and 584 348 (45.54%) lived in the Pearl River Delta of Guangdong. A total of 432 326 (33.69%) obtained junior high school education or lower. Self-reported hepatitis B vaccination rate decreased with increasing age (table 1).
The trend of HBV infection status among couples in Guangdong from 2014 to 2017 was presented in table 2. Overall, 161 204 individuals (12.56%) were positive for HBsAg, showing that the participant was infected with HBV (table 2). A total of 47 318 (3.69%) were positive for both HBeAg and HBsAg, which meant a high level of infection. On the other hand, 584 611 (45.56%) were positive for only anti-HBs (isolated anti-HBs), indicating the participant was immune to HBV due to prior vaccination; whereas 420 638 (32.78%) were negative for all HBV makers, suggesting that they were never exposed and thus susceptible to HBV. In terms of annual prevalence, we did not observe a linear trend of HBsAg positivity but frequent fluctuations during the study period, with the lowest prevalence in 2015 (12.10%). The trends of other test results were similar to that of HBsAg positivity, with the lowest prevalence in intermediate years (HBsAg+ and HBeAg+: 3.41% in 2016; isolated anti-HBs+: 44.24% in 2017; all negativity: 31.71% in 2015).
Table 2 also showed that the prevalence of all HBV markers varied significantly by the following factors. First, the prevalence of all HBV markers varied significantly by household registration groups (all p<0.01). The prevalence of HBsAg (12.77%), HBsAg and HBeAg (namely the coexistence of HBsAg and HBeAg, 3.77%), and isolated anti-HBs (45.61%) in people with Guangdong household registration was significantly higher than in those with non-Guangdong household registration, and there was a significantly lower prevalence of all negativity in people with Guangdong household registration (32.75%) than those with non-Guangdong household registration. Second, we observed the prevalence variance of all HBV markers by region groups (all p<0.01). The prevalence of HBsAg (13.26%), HBsAg and HBeAg (4.31%), and all negativity (38.84%) in couples living in the non-Pearl River Delta was significantly higher than those living in the Pearl River Delta, and the prevalence of isolated anti-HBs in couples living in the non-Pearl River Delta (41.78%) was significantly lower than those living in the Pearl River Delta. Third, the prevalence of all HBV markers varied significantly by age group (all p<0.01). HBsAg prevalence significantly increased with increasing age, while the prevalence of HBsAg and HBeAg significantly decreased with increasing age (all p<0.01). Fourth, the prevalence of HBsAg, and HBsAg and HBeAg was significantly higher in men than in women (all p<0.01).
Specifically, the HBsAg prevalence by household registration, region and hepatitis B vaccination history according to the selected characteristics was shown in figures 1–3. For all age, gender, ethnicity, education, occupation and region groups, the HBsAg prevalence was consistently higher in participants with Guangdong household registration than those with household registration from other provinces (figure 1). For most age, gender, ethnicity, education, occupation and hepatitis B vaccination history groups, the HBsAg prevalence was higher in participants living in the non-Pearl River Delta than those living in the Pearl River Delta (figure 2). For all age, gender, ethnicity, occupation, education and household registration groups, the HBsAg prevalence was higher in unvaccinated subjects than vaccinated ones (figure 3).
Furthermore, for the HBsAg prevalence of 641 642 couples, 12 446 couples (1.94%) were both positive; in 51 849 (8.08%), only the wife was positive; in 84 463 (13.16%), only the husband was positive (table 3). The HBsAg prevalence was significantly lower in the couples who were both vaccinated (18.63%) compared with the couples who were both unvaccinated (24.46%, p<0.05). The HBsAg prevalence of the husband alone was lowest in couples where only the husband was vaccinated (9.58%) and highest in couples where only the wife was vaccinated (19.65%, p<0.05). The HBsAg prevalence of the wife alone was lowest in couples where only the wife was vaccinated (5.76%) and highest in couples where only the husband was vaccinated (12.98%, p<0.05).
To the best of our knowledge, this is the first study that involved a large number of couples from both rural and urban areas in a high-epidemic region. Overall, there was a high HBsAg prevalence among the participants in Guangdong, China. Specifically, HBsAg prevalence was higher among couples with Guangdong household registration than those with non-Guangdong household registration, living in the non-Pearl River Delta than those living in the Pearl River Delta, and unvaccinated than vaccinated. The findings of this study can be used to guide the future adaptation of HBV-related strategies among couples of childbearing age in China and add to the understanding of HBV prevention in developing countries.
In the current study, the high HBsAg prevalence of the participants (12.56%) suggested that married couples could be categorised into a high-epidemic group, and this was concordant with previous findings from the Pearl River Delta in 2016, in which the HBsAg prevalence was 12.71% among residents aged 23–59 years.5 However, when compared with the couples reported in other studies, the HBsAg prevalence in this study was much higher than that of rural couples in China (4.80%~6.07%) and married couples in other countries (1.7%~10.9%).12–14 17–22 All of these implied the relatively high HBV burden of this population in Guangdong, which presents a significant public health threat and requires urgent interventions.
Those with non-Guangdong household registration, namely interprovincial migrants, had a lower HBsAg prevalence than the native population in Guangdong. This phenomenon could be probably explained through the following aspects. First, the historical HBsAg prevalence in Guangdong was high and this meant the native population has a high probability of being infected with hepatitis B.23 Second, some alleles were found to be strongly related to the HBV infection and there was a clear difference in genotype distributions between the southern and northern Chinese populations.24 The disparity in the genetic background might be a potential factor for the susceptibility of the native population. In general, the causes of high prevalence in Guangdong have been rarely investigated, and more related research is called for to provide insight into this problem. Additionally, our data showed that the interprovincial migrants had a high HBsAg prevalence (9.42%), which was above the national average. Substantial evidence found that migrants tend to have limited disease knowledge and low engagement in the health services of the host country, increasing their risk of HBV infection.25 Furthermore, relevant literature showed that migrants originating from a low-epidemic region had a higher HBV exposure when living in the high-epidemic regions.26 All these unfavourable circumstances contributed to the high HBsAg prevalence of the interprovincial migrants in Guangdong, and these migrants should not be neglected for future HBV prevention either.
Our study observed that the HBsAg prevalence was higher among those living in the non-Pearl River Delta than those living in the Pearl River Delta. One research describing HBV epidemiology in the Beijing–Tianjin–Hebei area of China found that the high-risk region was mainly distributed in underdeveloped rural areas, and this spatiotemporal pattern was strongly associated with socioeconomic factors.27 It is widely acknowledged that the Pearl River Delta is much wealthier than the non-Pearl River Delta and the region-specific difference of HBsAg prevalence in Guangdong might be related to their disparities in economic level. Possibly, people in the less developed areas have a lower standard of living and worse access to health services, increasing the risk of HBV transmission in this region. It was also reported that there was a low coverage rate of HBV vaccination in rural areas and its residents faced economic barriers to vaccination such as travel costs and user fees.28 Consequently, public health resources should be reasonably allocated in the future according to the variety of regions. More efforts are needed to improve local sanitation and ensure affordable medical services in the non-Pearl River Delta.
There was a lower HBsAg prevalence among the vaccinated couples than the unvaccinated ones, which was consistent with the finding that HBV vaccination was effective for prevention.29 30 Isolated anti-HBs prevalence was 45.56%, suggesting nearly half of the participants were protected by the vaccination. However, there was also 32.78% with all HBV markers negative, indicating a large number of the couples were still susceptible. In our study, HBV infection was a serious health problem in couples across all three age groups but the prevalence increased with increasing age. This age trend was similar to the finding in the general population.31 Combined with the higher proportion of vaccinated couples aged 20~29 years old in our result, we can infer that those aged 20~29 years old and born after 1992 had a higher probability of hepatitis B immunisation, which decreased the risk of HBV infection. As the three-child policy came out in 2021 in China, more couples aged 30~39 years old might consider having their third child, and this subgroup should be given greater attention.32 Specific methods such as expanding the immunisation programme and reintensifying antibody level for adults who have HBV-positive partners are recommended to curb the horizontal transmission of HBV among married couples.33 Moreover, the high prevalence of HBV among women (10.02%) in this study also implied a substantial need for perinatal postexposure prophylaxis to prevent mother-to-infant transmission in the future.
Our study has several limitations. First, the HBV-DNA load was not tested and liver function was not fully examined, which made it impossible for us to make a more complete analysis of the participant’s HBV infection status. Second, the history of vaccination was self-reported by the participants and the medical record was not available, where recall bias might occur. Third, bias might be introduced due to the exclusion of some couples with missing data in HBV testing results or other important variables. Fourth, our study targeted married couples aged 20–49 years. However, this restricts the generalisability of our results to other countries. Fifth, our sample comprised a low percentage (6.16%) of those with non-Guangdong household registration, while over 20% of the population in Guangdong was reported to have non-Guangdong household registration in 2021. Non-Guangdong residents might have more obstacles to obtaining the service and a lower acceptance of the project than native residents. Therefore, there may be selection bias in our sample, limiting its representativeness of all reproductive couples in Guangdong.
In conclusion, Guangdong is categorised as a high-epidemic region for hepatitis B, and couples of reproductive age had a relatively high HBsAg prevalence (12.56%) in this province. Specifically, the couples with Guangdong household registration, living in the non-Pearl River Delta and without a history of hepatitis B vaccination had a higher HBsAg prevalence. This study demonstrated the epidemiological features of HBV infection among married couples in a high-epidemic region and had potential implications for effectively reducing both vertical and horizontal transmission of HBV. The outcome emphasised the importance of improving access to medical resources in the non-Pearl River Delta, strengthening perinatal postexposure prophylaxis of pregnant women and increasing adult vaccine coverage among those with an HBV-positive partner.
Data availability statement
No data are available.
Patient consent for publication
The national project was approved by the institutional review board of the National Research Institute for Family Planning, China, and all participants’ written informed consent was obtained. The present study was executed jointly by the Guangdong Institute of Family Planning Science and Technology and Guangdong Women and Children Hospital, and approved by the institutional review board of Guangdong Women and Children Hospital (202101285).
ZL and JQ contributed equally.
Contributors QZ accepted full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. ZL, JZ and QZ designed the study. JY, JZ and QZ collected data and supervised the study. ZL and JQ analysed the data and wrote the draft manuscript. QX revised the draft manuscript. All authors discussed the results and contributed to the final manuscript. All authors read and approved the final manuscript.
Funding This work was partially supported by Medical Science Foundation of Guangdong Province (C2020034).
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.