Worldwide, hepatitis B virus (HBV) is associated with substantial morbidity and mortality. An estimated 254 million persons were living with chronic HBV infection and an estimated 1.1 million persons died from HBV-related causes, primarily cirrhosis and liver cancer, globally in 2022. Of these, the World Health Organization (WHO) European Region accounted for 10.6 million and 32,000 persons, respectively [1].

Hepatitis B remains a substantial public health problem in Uzbekistan, a lower-middle income country in Central Asia and a Member State of the WHO European Region (2023 population, 36 million) [2]. Historically, Uzbekistan was considered a country with high-intermediate to high level of HBV endemicity.¹ Estimates of prevalence of chronic HBV infection in Uzbekistan based on statistical modelling suggest a high burden in the pre-vaccine era with prevalence of HBV surface antigen (HBsAg), a marker of chronic/active HBV infection, between 5.51 % and 13.1 % [3–8]. Recent estimates indicate decline in overall HBsAg prevalence in the general population to intermediate levels (range of estimates for all ages, 2.1 %–4.3 %; for children <5 years – 0.1 %–0.4 %) [8,9]. However, no nationally representative population-based serosurveys have been conducted to directly measure HBV infection prevalence in Uzbekistan.

A safe and effective vaccine against hepatitis B has been available for more than 30 years [10]. Hepatitis B vaccine introduction into the national immunization schedule of Uzbekistan began in 1997 in parts of the country, with nationwide introduction in October 2001 [11]. Initially, the national immunization schedule comprised three doses of monovalent hepatitis B vaccine, including birth dose. Since the introduction of pentavalent vaccine containing diphtheria, tetanus, whole cell pertussis, Hemophilus influenzae type B, and hepatitis B components (DTwP-HiB-HepB) in 2009, the following schedule has been in place: hepatitis B monovalent vaccine (pediatric) at birth (recommended within 24 h of life) and pentavalent vaccine at 2, 3 and 4 months. Reported immunization coverage with hepatitis B vaccine in Uzbekistan has been historically very high (Fig. 1). WHO-UNICEF estimates concur with officially reported data [12]. A Multiple Indicator Cluster Survey (MICS) conducted in 2006 has also shown high coverage [13].

Coverage with ≥3 doses of hepatitis B vaccine (HepB3) has been ≥95 % for all years since 2003 except 2008, when HepB3 coverage was 91 % because of a vaccine stockout.² Coverage with the birth dose of hepatitis B vaccine (HepB-BD) has also been consistently ≥95 % since 2002, except for 2010, when HepB-BD coverage fell to 48 % because of supply problems related to changes in the vaccine procurement mechanism in Uzbekistan (Fig. 1). Coverage with hepatitis B vaccine is uniformly high throughout the country, without any substantial subnational variations.

Implementation of hepatitis B vaccination through routine immunization programs of many countries beginning in the late 1980s has helped to dramatically reduce the HBV infection prevalence even in settings of high endemicity [14–19]. In Uzbekistan, the surveillance data for acute hepatitis B infections also suggest a substantial decline over the last two decades (unpublished data, MOH; Fig. 2), although other factors, such as improvement of hygienic standards in medical procedures, and injection and blood safety, have likely contributed to the overall decline.

Uzbekistan has endorsed the WHO goal of elimination of viral hepatitis as a public health threat by 2030, adopted by World Health Assembly in 2016 [20–22]. As an interim step towards elimination, Uzbekistan has also adopted the regional hepatitis B control goal set by the WHO European Region in 2015, with a target of <0.5 % prevalence of chronic HBV infection in vaccinated cohorts [23–26].

The Regional Hepatitis B Working Group of the European Technical Advisory Group of Experts on Immunizations (ETAGE) developed a framework and criteria for validation of the achievement of regional hepatitis B control goals by countries [24]. In addition to achieving the impact target of <0.5 % HBsAg prevalence, validation of the achievement of regional hepatitis B control goal by countries requires demonstration of ≥90 % coverage with timely hepatitis B-BD (i.e. administered within 24 h of birth) and HepB3 for at least three years [24].

Although hepatitis B vaccine has been used in Uzbekistan with high coverage for more than 20 years, no population-based assessments of the impact of hepatitis B vaccination in Uzbekistan have been previously implemented. Therefore, we conducted a cross-sectional survey of the prevalence of HBsAg, a marker of chronic HBV infection, to obtain population-based data on HBV infection prevalence among children in Uzbekistan, assess the impact of hepatitis B vaccination, measure progress towards achieving regional hepatitis B control goal, and help to better characterize the burden of hepatitis B in the country. The survey also provided an opportunity to assess hepatitis B vaccination status of the surveyed population.

The present survey, the first population based national hepatitis B serosurvey in Uzbekistan, revealed that nationwide HBsAg prevalence among children enrolled in primary school grades 1–3 in 2021 was low at 0.20 % (95 % CI, 0.09 %–0.38 %). This level of HBsAg prevalence among children is below the 0.5 % European regional hepatitis B control target [23,24], demonstrating the profound impact of more than 20 years of successful routine hepatitis B vaccination in Uzbekistan.

The results of this serosurvey, in combination with high reported coverage with timely HepB-BD and ≥ 3 doses of hepatitis B-containing vaccines, were instrumental in validating Uzbekistan’s achievement of the European regional hepatitis B control goal by the ETAGE Hepatitis B Regional Working Group in 2023 [36]. The formal process of validation of the achievement of hepatitis B control by the countries in the European Region was initiated in 2019. As of 2023, nine of the 53 Member States have been validated, including Uzbekistan⁴ [36].

To ensure continued low prevalence of HBV infection among children in the future, high infant immunization coverage with a timely HepB-BD and the full series of ≥3 doses of hepatitis B-containing vaccines in Uzbekistan will be needed. With sustained high coverage, overall HBsAg prevalence in Uzbekistan’s general population will likely further decline as more vaccinated cohorts reach adulthood, and the burden of hepatitis B in Uzbekistan will increasingly shift to age groups born before vaccine introduction.

The survey also demonstrated that the country has made substantial progress towards achieving the elimination of mother-to-child transmission (MTCT) of HBV, the major cause of chronic HBV infections [25,37,38]. Elimination of HBV MTCT is an essential component of the elimination of viral hepatitis as public health threat and has recently been included, along with the elimination of MTCT of HIV and syphilis, as the third component of the WHO “triple elimination” initiative [37,38]. WHO has defined HBsAg prevalence of ≤0.1 % as the impact indicator of the global elimination of mother to-child transmission [25,37–39].

The key intervention to prevent MTCT of HBV is vaccination of newborns with hepatitis B vaccine at birth, ideally within 24 h [10]. Timely HepB-BD is extremely effective in preventing perinatal transmission of HBV [10]. However, protection is not 100 % and transmission could still occur in certain situations, e. g. when mother’s HBV viral load is very high or when the virus is transmitted before birth. Therefore, in addition to timely HepB-BD vaccination, WHO also recommends additional interventions to prevent MTCT of HBV including antenatal screening of pregnant women for hepatitis B, administering hepatitis B immunoglobulin (HBIG) at birth to infants born to eligible HBsAg-positive mothers, and antiviral treatment of HBsAg-positive pregnant women [10,40,41].

High coverage with HepB-BD in Uzbekistan has clearly contributed to the observed low levels of HBsAg among children. However, strengthening additional interventions to prevent MTCT is needed. Currently, antenatal screening of pregnant women for hepatitis B is in place, but the coverage with screening is not systematically monitored. HBIG for newborns of HBsAg-positive mothers and antiviral treatment for eligible pregnant women are not currently available in Uzbekistan. To decrease HBsAg seroprevalence to levels consistent with the elimination of MTCT of HBV, antenatal screening for hepatitis B of all pregnant women and systematic monitoring of coverage with antenatal screening are needed in all regions of in Uzbekistan. Antiviral treatment with tenofovir for eligible HBsAg-positive pregnant women is also needed. Implementation of recently updated WHO guidelines for chronic HBV infection treatment with simplified eligibility criteria for pregnant women in resource-limited settings could help increase access to treatment for HBsAg-positive pregnant women in Uzbekistan [41]. In addition, policy makers could consider the feasibility of providing of HBIG at birth to infants born to HBsAg-positive mothers.

Along with achieving the elimination of MTCT of HBV, countries must meet several other programmatic and impact indicators reflecting the reduction of disease burden and successful implementation of preventive interventions in order to achieve the elimination of viral hepatitis as a public health problem by 2030 [22,39,41]. Addressing the substantial burden of HBV in Uzbekistan has been long recognized as a priority [7,42–45]. The success of the national hepatitis B vaccination program has created solid foundation for the elimination of hepatitis B elimination as a public health threat. However, implementation of other key interventions for viral hepatitis elimination, such as large-scale population screening, linkage to care and provision of antiviral treatment, implementation of preventive measures in key populations, and strengthening infection prevention and control practices, has been challenged by the insufficient resources.

Because of the lack of any major donor-funded initiatives supporting viral hepatitis elimination in low- and middle-income countries, viral hepatitis elimination activities in Uzbekistan have been expanding gradually. The Ordinance N°537 of the Cabinet of Ministers from 24 July 2017 (“On additional measures to prevent spread of infectious diseases in the Republic of Uzbekistan”) identified viral hepatitis as one of the priority areas. The following year, the Ministry of Health Decree N°542 from 27 August 2018 (“On further improvement of diagnostics, treatment and prevention of viral hepatitis in the Republic of Uzbekistan”) defined strategies to achieve viral hepatitis-related goals in Uzbekistan. A pilot program using a catalytic funding model and simplified test-and-treat strategies was implemented in Tashkent in 2019–2020. Despite challenges created by the COVID-19 pandemic, over 60,000 persons were screened for hepatitis B and C using rapid tests, approximately 1600 were diagnosed with chronic HBV infection for the first time and approximately 300 received antiviral treatment through this demonstration project [46,47]. In 2022, two presidential ordinances endorsed expansion of viral hepatitis elimination program in Uzbekistan through 2025 and allocated budget to increase HBV and HCV screening up to 1 million persons annually, establish the national electronic registry for chronic liver disease, provide antiviral treatment to HCV-infected persons, and hepatitis B vaccination to healthcare workers in contact with blood [48,49]. The finalization of the national strategic plan for viral hepatitis elimination, currently under development, will help to identify innovative approaches to implementation of viral hepatitis elimination and ensure continued expansion of these efforts throughout Uzbekistan.

The present serosurvey had certain limitations. The narrow age range of the serosurvey limited generalizability of its findings to all age cohorts of children in Uzbekistan. However, consistently very high routine infant immunization coverage for hepatitis B over the years should have reduced the impact of this limitation. The small number of HBsAg positive children limited statistical power of the survey for this group, preventing detailed analysis of seroprevalence by sex, region, or age cohort. Immunization records were not available for all children, and, on rare occasions, the date of HepB-BD given at the maternity hospital was not transferred to the immunization card stored at the primary health care facility. However, such instances were infrequent and should not have had substantial impact on the representativeness of the immunization status of children. In addition, to reduce participation bias, we requested immunization records for all children in the selected classes, irrespective of their participation status and were able to collect immunization records for the vast majority of targeted children.

Overall, this serosurvey documented success of Uzbekistan’s national immunization program and provided data in support of feasibility of the elimination of HBV in the country. The experience and lessons learned from implementing the elimination program in Uzbekistan, which has been among the first in Central Asia to undertake this initiative, will be helpful to neighboring countries, as well as other low- and middle-income countries who often encounter similar challenges.