Hepatitis B virus (HBV) infection remains a major global health challenge, with current estimates indicating 254 million chronic carriers worldwide and approximately 1.1 million deaths in 2022. As the seventh leading cause of global mortality, HBV accounts for 29% of cirrhosis-related deaths. Chronic HBV infection progresses through distinct clinical stages, ultimately leading to cirrhosis, liver failure, and hepatocellular carcinoma. Particularly concerning is vertical transmission from mother to child, which persists as a predominant transmission route in resource-limited settings where prenatal screening coverage remains suboptimal (1). Vertical transmission efficiency reaches 90% in neonates born to HbsAg or HbeAg positive mothers without intervention (2). While prevention protocols have been widely promoted, implementation gaps persist in low-resource settings due to systemic challenges in healthcare infrastructure and antenatal screening accessibility. These challenges demand targeted interventions for WCBA, particularly in resource-limited settings (3).

The United Nations Sustainable Development Goals (SDGs) specifically target maternal mortality reduction (4). Recent WHO guidelines (2024) further recommend routine antenatal HBV DNA screening for women of childbearing age to curtail mother-to-child transmission (5). Howerver, chronic HBV continues to disproportionately affect women of childbearing age (WCBA) worldwide. As a partially double-stranded DNA virus transmitted via body fluids, HBV poses a dual threat to maternal-fetal health. Meta-analyses have demonstrated significantly elevated risks of preterm birth and gestational diabetes among infected mothers (6, 7). The natural history of chronic HBV infection typically progresses through immune-tolerant, immune-active, and inactive phases, with modifiable factors such as alcohol consumption accelerating fibrosis through increased oxidative stress and suppression of antiviral immunity. These risk factors substantially contribute to HBV-related morbidity. Emerging epidemiological evidence indicates that in 2019, 33.73% of hepatitis B-related age-standardized deaths were attributable to tobacco use, alcohol consumption, and high BMI—a notable increase from 1990, when 28.23% of deaths were linked to these same factors (8). Despite these documented interactions, critical knowledge gaps persist regarding the global epidemiology of HBV in WCBA populations, particularly concerning alcohol consumption patterns. This evidence gap may inadvertently undermine progress toward SDG health targets.

To address the limitations of existing research and enhance the global understanding of the epidemiology of hepatitis B in WCBA, particularly in relation to alcohol consumption, this study utilizes data from the Global Burden of Disease (GBD) 2021. It aims to provide a comprehensive and updated evaluation of the disease’s impact and trends. The objectives are threefold: First, to conduct a descriptive epidemiological analysis globally, within five Sociodemographic Index (SDI) regions, and across 204 countries and territories. Sencond, to perform trend analysis and demographic-epidemiological decomposition to elucidate the factors influencing these trends. Third, to forecast the global burden through 2040, offering a forward-looking perspective on the projected trajectory of the disease.

This study highlights the increasing burden of hepatitis B attributable to alcohol among WCBA from 1990 to 2021. Globally, we observed a paradoxical trend: while the absolute case numbers of deaths and DALYs rose from 1990 to 2021, ASRs declined. This dichotomy reflects two competing forces: population growth driving case numbers and improved prevention reducing relative risks. Notably, the 1999–2005 DALY rebound coincided with three pivotal events: the Asian financial crisis, accelerated urbanization in sub-Saharan Africa, and the global obesity pandemic onset (19, 20).

Our SDI stratification revealed three-tier disparities: 1. Prevention gap. Low-SDI regions had 43% lower HBV vaccination coverage compared with higher SDI counterparts (21). 2. Diagnostic delay. Time-to-diagnosis in sub-Saharan Africa averaged 8.2 years compared with 2.1 years in Western Europe (22). 3. Alcohol interaction. Each 10 g/day alcohol intake amplified hepatocellular carcinoma risk by 38% in HBV-positive individuals compared with 12% in HBV-negative populations (23). These systemic disparities further underscore a critical limitation in current global burden estimates: GBD figures may overestimate the burden in high-SDI regions due to enhanced case detection, while simultaneously underestimating it in low-SDI regions with underdeveloped surveillance systems.

Emerging therapeutic strategies focusing on cccDNA elimination, exemplified by CRISPR-based gene editing systems, and approaches targeting HBsAg secretion through RNA interference platforms demonstrate significant potential (24). However, deployment challenges persist in resource-limited regions, where median annual treatment costs of 23,000 dollars surpass the average per capita healthcare expenditure across 32 nations by 15-fold. Furthermore, stringent temperature-controlled distribution networks remain largely inaccessible in rural areas, as evidenced by operational refrigeration systems in merely 28% of sub-Saharan African medical institutions. These implementation barriers highlight the critical need for concurrent advancements in both breakthrough treatments and foundational public health systems (25, 26). Compounding these structural limitations, the COVID-19 pandemic has disrupted childhood immunization, threatening progress toward elimination of hepatitis B by 2030. The paper reported the number of expected and excess HBV infections and related deaths after 10 and 20% decreases in hepatitis B birth dose or third-dose hepatitis B vaccination coverage of children born in 2020 compared with prepandemic 2019 levels (27). Smoking was not modeled in GBD. Future studies should adjust for these using individual-level data.

The 4.3-fold DALY disparity stems from a syndemic interaction: First, structural: 78% of low-SDI countries lack national alcohol control policies compared with 22% of high-SDI countries. Second, biological: the alcohol-metabolizing ADH1B2 allele frequency is 2.3% in sub-Saharan Africa compared with 68% in East Asia, exacerbating hepatotoxicity risk (28). Third, healthcare: median time-to-antiviral therapy initiation is 5.7 years in low-SDI regions compared with 0.8 years in high-SDI regions (29).

The BAPC modeling forecasts contrasting epidemiological trajectories, projecting an escalation in global HBV-related disability-adjusted life years by 2040 under current intervention patterns. Three synergistic mitigation strategies demonstrate transformative potential: First, elevating hepatitis B birth-dose vaccination rates to 90% coverage across sub-Saharan Africa, where current immunization rates stagnate at 46%, could avert an estimated 7.1 million vertical transmissions. Second, systematic adoption of the WHO SAFER framework’s five alcohol control pillars which are strengthening restrictions, advancing enforcement, facilitating treatment, enforcing advertising bans, and raising taxation, promises 34% reductions in alcohol-attributable disease burden. Third, synergistic integration of HBV screening with routine antenatal services shows particular efficacy in curbing mother-to-child transmission rates, potentially decreasing from the baseline 8.3% to below 2% through enhanced detection and immunoprophylaxis protocols (30, 31).

This study advances the understanding of alcohol-attributable HBV burden among WCBA by integrating temporal trends, socioeconomic stratification, and forward-looking projections—a perspective underexplored in existing literature. While prior studies have focused on HBV epidemiology or alcohol-related liver disease in isolation, our analysis uniquely quantifies their syndemic interaction at a global scale, emphasizing the compounded risks faced by WCBA in low-resource settings. By linking population growth, delayed diagnostics, and genetic susceptibility, we provide a mechanistic framework to explain regional divergences in burden trends, thereby contextualizing the urgency of tailored interventions.

However, several limitations warrant consideration. First, GBD estimates rely on modeled data, which may underestimate HBV prevalence in regions with fragmented surveillance systems, particularly sub-Saharan Africa and conflict zones. Second, the BAPC projections assume linear trends in healthcare access and alcohol consumption, potentially overlooking nonlinear disruptions such as pandemic-induced healthcare delays or rapid policy shifts. Third, while alcohol’s attribution is quantified via comparative risk assessment, residual confounding from unmeasured factors, such as aflatoxin exposure or viral co-infections, could inflate risk estimates. Finally, the GBD database relies on standardized modeling across countries, which may mask regional variations in data quality, particularly in settings with incomplete vital registration systems or limited HBV testing capacity, leading to potential misclassification biases.

Our findings harmonize with and extend current paradigms. The transient DALY rebound (1999–2005) aligns with historical crises, underscoring how macroeconomic instability exacerbates health disparities—a dimension rarely integrated into HBV burden analyses. Furthermore, the disproportionate burden in low-middle SDI regions challenges the conventional focus on high-prevalence endemic areas, advocating for a dual-strategy approach: accelerating vaccine coverage while concurrently addressing alcohol consumption as a modifiable comorbidity.

Ultimately, this study underscores that HBV elimination in WCBA demands not only biomedical innovation but also socioeconomic equity. By bridging demographic, genetic, and policy lenses, we redefine the challenge as one of intersecting vulnerabilities—a paradigm shift with implications for global hepatitis governance.

In conclusion, this GBD study offers an extensive overview of deaths and DALYs attributable to hepatitis B resulting from alcohol consumption among WCBA on a global scale, across 5 SDI regions, and within 204 countries and territories worldwide from 1990 to 2021. The study also projects trends through to 2040. It reveals a general upward trend in the global disease burden, albeit with a slowing rate of increase from 1990 to 2021. Notably, in low SDI regions, the impact of hepatitis B due to alcohol among WCBA is characterized by elevated deaths and DALYs. The period from 1999 to 2005 was particularly challenging due to the substantial disease burden experienced globally. Currently, demographic shifts, including aging populations and population growth, are the primary drivers of this burden. These findings underscore the significant challenge posed by the control and management of hepatitis B related to alcohol consumption among WCBA. Looking ahead, with the expansion of medical resources and the ongoing refinement of public health policies, it is anticipated that the disease burden will be reduced, particularly in rapidly developing economies such as China. Health, education, and finance sectors must work together, for example by adding HBV screening to maternal health services and by enforcing alcohol taxes in low-SDI regions.