Trends in hepatitis B notification rates in Guangzhou, China, between 2009 and 2020: an epidemiological study

Hepatitis B is caused by infection with the hepatitis B virus (HBV) and has become a major global public health problem [1, 2]. The latest data from the World Health Organization (WHO) revealed that 296 million people were living with chronic hepatitis B (CHB), and hepatitis B resulted in an estimated 820,000 deaths worldwide in 2019 [3]. Several studies have shown that the prevalence of hepatitis B varies by geographical region, with infection rates of < 2% in the United States and Western Europe, 2–8% in the Mediterranean and South America, and up to 20% in Asia and Africa [4‐6]. In addition, significant sex, age, race, and urban–rural differences in HBV infection are frequently reported, although these reports are not consistent [5, 7, 8]. For example, a meta-analysis of Chinese populations reported that the prevalence of HBV infection was higher in men than in women and in rural rather than urban areas [7], but an Iranian study found that the rate of infection was higher in the urban areas [8].

Hepatitis B virus is highly contagious and transmitted primarily via perinatal and percutaneous routes and sexual exposure as well as by close person-to-person contact, presumably via open cuts and sores [9]. HBV is highly resistant, surviving up to 30 days at room temperature on dry surfaces [10]. Individuals with CHB infection are at an increased risk of developing HBV-related liver diseases, such as liver cirrhosis and hepatocellular carcinoma (HCC) [11, 12]. Studies have shown that 15–40% of people with CHB infection develop cirrhosis, HCC, or liver failure, and 25% die prematurely from these complications [9, 13‐15].

In China, a national epidemiological survey reported that the positive rate of hepatitis B surface antigen (HBsAg) in the Chinese population was 7.20% in 2006. However, the positive rate in Guangdong Province was 11.10% during the same period, which was much higher than the national average [16]. Guangzhou is the capital of Guangdong province, located in the south of China (Fig. 1), with a resident population of 18.7 million in 2020, a developed economy, and frequent movement of people. The most recent large-scale population-based epidemiological survey of hepatitis B in 2018 demonstrated that the rate of HBsAg positivity in the Guangzhou population was 12.45% [17], which was higher than the national rate and the provincial rate in 2006 [16, 18]. Unfortunately, few studies have investigated the changing trends in hepatitis B infection in Guangzhou.

This study aimed to describe the trends in the reported prevalence of HBV infection in Guangzhou between 2009 and 2020 in order to provide a reference for the government to develop strategies and measures for the prevention of hepatitis B infection.

Liver disease caused by HBV infection has resulted in a huge disease burden worldwide, and CHB infection is particularly prevalent in Asia, specifically in China [23‐26]. HBV is transmitted in a complex and insidious manner; the primary modes of HBV transmission in Guangdong include mother-to-child transmission, family aggregate transmission, traumatic medical practices, and paid blood donation [27, 28]. In 2016, the WHO approved the first global health sector strategy for viral hepatitis, with the goal of eliminating viral hepatitis as a major public health threat by 2030 (reducing new infections by 90% and mortality by 65%) [24].

The present study aimed to describe the trends in the reported prevalence of HBV infection in Guangzhou between 2009 and 2020 in order to provide a reference for the government to develop strategies and measures for the prevention of hepatitis B infection. We found that the notification rate for new hepatitis B cases in Guangzhou decreased from 269.16 per 100,000 in 2009 to 141.73 per 100,000 in 2020, with an annual decrease of 6.30%. A long-term decreasing trend was noted in the notification rate of hepatitis B in Guangzhou, which can likely be attributed to a series of interventions and the introduction of relevant policies by the Chinese government. In 1992, a recombinant vaccine was licensed and introduced nationwide for a fee, requiring one dose of hepatitis B vaccine for all births and two additional doses during infancy, with the goal of interrupting perinatal HBV transmission and providing lifelong HBV protection for new-borns. In 2002, China included the hepatitis B vaccine in its Expanded Program on Immunization (EPI), providing free vaccinations for children aged < 14 years. In addition, between 2009 and 2011, a catch-up campaign was launched for children aged < 15 years, which succeeded in vaccinating approximately 68 million children [26, 29]. Despite the efforts of the government and significant decrease in the notification rate of hepatitis B in Guangzhou, the notification rate of 141.73 per 100,000 in 2020 is still significantly higher than that in certain developed western countries, such as the United States and European Union (EU) countries [30, 31], and Asian countries, including Japan and South Korea [32, 33], and is also higher than the national average of 69.05 per 100,000 in 2014 [34]. Guangzhou is still under tremendous pressure to achieve the 2030 target set by the WHO.

This study highlights a long-term decreasing trend in the notification rates in both sexes. The notification rate is currently significantly higher in men than in women, although this sex difference has decreased from 2.34-fold in 2010 to 1.54-fold in 2020, which is consistent with the reports from EU/European Economic Area countries in 2018 [31]. One of the main reasons for this observation is that variant oestrogen receptors are more highly expressed in male HCC patients than in female patients, leading to speculation that oestrogen may play a role in protection against HBV infection [35]. Moreover, China has implemented universal free mandatory hepatitis B vaccination, thus generating universal resistance in both men and women, which further reduced the sex difference in the prevalence of HBV infection.

In addition, this study also found that the notification rate in urban areas has been declining at an average annual rate of 7.75% since 2009. However, rural areas showed a brief decline from 2009 to 2012, after which it began to increase at an annual rate of 6.23%. The decline in urban morbidity may be attributed to the benefits of a series of government interventions and policies, such as the free EPI for Children aged < 14 years in 2002, and the 2009–2011 vaccine catch-up campaign for children aged < 15 years. The long-term increasing trend in rural areas since 2012 may be attributed to the increasing degree of urban–rural integration with the development of China's economy, which has significantly improved the level of medical care, medical resources, and the convenience of medical care for residents in rural areas; and the gradually increasing living standards, literacy, and awareness of medical care among rural residents. The combination of these factors has contributed to the increase in the diagnostic rate of hepatitis B in rural areas and the rate of medical consultation among the residents, ultimately leading to an annual increase in the notification rate of hepatitis B. The notification rate of hepatitis B in rural areas exceeded that in urban areas for the first time in 2017, and the gap widened annually, reaching 1.57-fold the rate in urban areas by 2020, which is inconsistent with the significantly higher prevalence of acute hepatitis B in urban areas than in rural areas reported in Poland and Norway [36, 37]. Possible explanations are that the prevalence of hepatitis B in these countries is low and many of the new cases are immigrants, who mostly live in urban areas [37, 38].

There was an overall decreasing trend in all age groups except 50–59 years and ≥ 60 years age groups. This may be primarily due to China's vaccination policy and the improvement of medical care, which effectively prevented the spread of hepatitis B transmission. The notification rate in the 50–59 years age group continued to rise until 2014, after which it began to decline, and in the group aged ≥ 60 years, after an increasing but not significant trend until 2015, the notification rate began to decline annually. We are unable to provide an explanation for the trends in the notification rate in these two age groups, and further studies are needed.

Our analysis had several strengths. First, with the continuous improvement of the CISDCP system and the increasingly standardized implementation of infectious disease reporting requirements by medical institutions, the CISDCP system includes almost all new cases of hepatitis B. One study indicated that the overall rate of underreporting of infectious diseases in Guangzhou is 1.17%, and the total rate of underreporting of infectious diseases of category B (to which hepatitis B belongs) is 0.36%; this rate is even lower if only hepatitis B is calculated [39]. Second, we included up to 12 years of data in the analysis, which greatly increased our ability to detect temporal trends and led to more consistent results. However, our study also has several limitations. First, although the underreporting rate of the CISDCP system was low, the consultation rate of hepatitis B patients was not available. It can be speculated from the annual increased notification rate in rural areas that there may still be numerous undiagnosed patients without symptoms in rural areas and that the true incidence of hepatitis B may be markedly higher than that observed in this study. Second, the purpose of this study was to analyze trends in the notification rate of hepatitis B in Guangzhou, and we were unable to quantify exposure to risk factors (such as the standard of living, awareness of access to medical care, and local level of medical care) that may contribute to the change in HBV infection tendencies. However, we believe that these external factors are gradual and continuous processes and should have little effect on the reported incidence in the approaching years.

The overall notification rate of hepatitis B in Guangzhou is decreasing annually; however, there has been an increasing trend in rural areas in recent years. Effective measures should be taken to control hepatitis B infection in Guangzhou, particularly in rural areas.