Global, regional, and national health inequalities in hepatitis B virus-related liver cancer in 204 countries, 1990-2021

doi:10.21203/rs.3.rs-5281121/v1

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Research Article

Global, regional, and national health inequalities in hepatitis B virus-related liver cancer in 204 countries, 1990-2021

https://doi.org/10.21203/rs.3.rs-5281121/v1

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Background

Hepatitis B virus-related liver cancer (HBV-LC) is a significant public health challenge, particularly in low- and middle-income countries. Despite advancements in vaccination and antiviral therapies, global disparities persist.

Objective

This study provides a comprehensive analysis of the global, regional, and national burden of HBV-LC from 1990 to 2021 and projects future trends to 2036, using data from the Global Burden of Disease (GBD) 2021 study.

Methods

Data on prevalence, incidence, mortality, and disability-adjusted life years (DALYs) were extracted from GBD 2021. Joinpoint regression was used to analyze trends, and Bayesian age-period-cohort (BAPC) models were employed to forecast future burden.

Results

In 2021, an estimated 288,106 global cases of HBV-LC were reported, with an age-standardized prevalence rate (ASPR) of 3.32 per 100,000 people. The global incidence rate (ASIR) was 2.37 per 100,000, while the mortality rate (ASMR) was 2.09 per 100,000. From 1990 to 2021, the ASIR declined by 0.22%, and the DALYs decreased by 0.79 years per 100,000. The highest burden was observed in East Asia and the High-income Asia Pacific region, while the lower SDI regions experienced more significant mortality. Projections from the BAPC model indicate continued declines in both ASIR and ASMR through 2036, particularly among females.

Conclusion

This study highlights a global reduction in the HBV-LC burden over the past three decades, yet significant disparities remain between regions. Future efforts should focus on expanding access to vaccination and antiviral therapies in low-SDI areas to further mitigate the disease burden.

Hepatitis B virus-related liver cancer (HBV-LC)

Global disease burden

Epidemiology

Joinpoint regression analysis

Health inequality

Prediction

Hepatitis B virus (HBV) infection remains one of the most prevalent and severe public health concerns worldwide, affecting an estimated 316 million people as of 2019(1, 2). Chronic HBV infection is a significant cause of liver disease, including liver cirrhosis and hepatocellular carcinoma, both of which contribute significantly to global morbidity and mortality(3, 4). Among these, liver cancer, particularly HBV-related liver cancer (HBV-LC), is one of the leading causes of cancer-related deaths globally(4–6).

Despite widespread HBV vaccination programs and the availability of effective antiviral treatments, the burden of HBV-LC remains substantial, particularly in low- and middle-income countries. The World Health Organization (WHO) has set a goal to eliminate HBV as a public health threat by 2030(7, 8). However, achieving this target has proven challenging owing to barriers such as limited healthcare access, late diagnosis, and persistent stigma associated with the disease, especially in resource-limited settings(9).

Although significant research has been conducted on other causes of liver cancer, such as non-alcoholic steatohepatitis(10), hepatitis C virus(11), and alcohol use(12), these studies often lack the level of detail needed to fully capture the differences in disease burden across socio-demographic groups and regions. Specifically, analyses of HBV-LC remain limited. For instance, a previous study using GBD 2019 data explored the global burden of primary liver cancer by five etiologies and provided forecasts up to 2035(5). However, the analyses of each liver cancer etiology, including HBV-LC, are relatively superficial, leaving significant gaps in our understanding of the specific burden, global distribution, and long-term trends of HBV-LC. This highlights the need for a more detailed and comprehensive analysis, particularly concerning sociodemographic and regional variations.

To address these gaps, the present study provides an in-depth analysis of the global, regional, and national burden of HBV-LC using data from the GBD 2021 study covering the period from 1990 to 2021. This study offers detailed subgroup analyses based on age, sex, and SDI score. It includes future projections using advanced statistical techniques such as joinpoint regression and the Bayesian age-period-cohort (BAPC) model. These insights will assist policymakers and healthcare providers in implementing targeted interventions to reduce the global burden of HBV-LC, especially in resource-limited regions, where the disease remains the most prevalent.

Data Acquisition and Sources

This study utilized data from the Global Burden of Disease (GBD) 2021 database, which provides comprehensive epidemiological estimates for diseases, injuries, and risk factors across 204 countries and regions. Data on the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) for HBV-LC were extracted from the Global Health Data Exchange (GHDx) platform managed by the Institute for Health Metrics and Evaluation (IHME). These estimates cover 369 diseases and injuries and 88 risk factors standardized for age and population size(13, 14). More information and direct data access are available through IHME’s official portal (https://ghdx.healthdata.org).

The socio-demographic index (SDI) was used to assess developmental status, which was calculated based on education level, fertility rate, and income per capita. SDI values range from 0 (lowest development) to 100 (highest development)(15). Countries were categorized into five groups: Low SDI (< 0.46), Low-middle SDI (0.46–0.64), Middle SDI (0.65–0.74), High-middle SDI (0.75–0.85), and High SDI (> 0.85)(16).

Joinpoint Regression Model

The Joinpoint regression model was applied to detect significant changes in the trends over time. This method is particularly suited for identifying inflection points, that is, moments when the direction or magnitude of a trend changes. The model divides the timeline into discrete segments and fits the data with multiple linear regression lines joined at the detected inflection points(17).

The key parameters include the annual percent change (APC), which measures the rate of change in a segment, and the average annual percent change (AAPC), which summarizes the overall trend across the entire period(18). Statistical significance was determined using the 95% confidence interval (CI) for APC or AAPC, with significance established if the CI excluded zero.

Measurement Health Inequalities

We analyzed the total DALYs and age-standardized DALY rates to assess income-related health disparities. Following WHO recommendations, we employed two standardized measures: the slope index of inequality (SII) and the concentration index (CI)(19, 20). SII represents the regression slope between country-level DALYs and healthcare facility availability. At the same time, the relative inequality index (RII) was derived by dividing the SII by the global age-standardized death rate (ASDR). The CI was calculated using the Lorenz curve of cumulative DALYs relative to population size, with CI values ranging from − 1 to 1, where negative values indicate a higher burden in lower-SDI countries.

Bayesian Age-Period-Cohort (BAPC) Model Prediction

To project future trends in HBV-LC burden, we employed the Bayesian Age-Period-Cohort (BAPC) model, which incorporates demographic data and considers age, period, and cohort effects. This model allows us to estimate how disease incidence and mortality will evolve, taking into account shifts in population structure, changes in healthcare practices, and broader societal influences(21).

The BAPC model uses a Bayesian framework that integrates prior knowledge and observed data. For this study, demographic projections were downloaded from the GBD 2021 database, and the model was implemented using R software (version 4.3.2) with the "BAPC" and "INLA" packages. The priors of the model were specified based on historical trends observed from 1990 to 2021, and the projections were validated against known disease dynamics(22, 23). This approach provides robust estimates of future trends in age-standardized incidence rates (ASIR) and mortality rates (ASMR), which are beneficial for long-term health planning and resource allocation.

Statistical Analysis

Prevalence, incidence, mortality, and DALYs for HBV-LC were reported per 100,000 individuals with corresponding 95% uncertainty intervals (UIs). Statistical analyses and visualization were conducted using the WHO Health Equity Assessment Toolkit and R software (version 4.3.3). Statistical significance was considered at p < 0.05 for all analyses(24, 25).

Global Trends

In 2021, there were an estimated 288,106 global cases of HBV-LC (95% UI: 237,812 to 349,750), with an ASPR of 3.32 per 100,000 people (95% UI: 2.74 to 4.02) (Table 1). The global incidence was 206,366 cases (95% UI: 169,401 to 252,050), with an ASIR of 2.37 per 100,000 people (95% UI: 1.95 to 2.89) (Table 1). Between 1990 and 2021, ASIR decreased by 0.22 per 100,000 (95% UI: -0.27 to -0.17). In 2021, the number of HBV-LC-related deaths was 181,194 (95% UI: 148,896 to 221,685), and the ASMR was 2.09 per 100,000 (95% UI: 1.72 to 2.55), reflecting a reduction of 0.54 per 100,000 from 1990 (95% UI: -0.81 to -0.27). The global DALYs burden in 2021 was 5,668,199 (95% UI: 4,706,886 to 6,885,071), with an age-standardized DALY rate of 65.36 per 100,000 (95% UI: 54.43 to 79.35), representing a decline of 0.79 per 100,000 from 1990 (95% UI: -0.99 to -0.59).

Regional Trends

In 2021, regions with an intermediate SDI had the highest ASPR for HBV-LC at 4.38 per 100,000 (95% UI: 3.50 to 5.54) (Table 1). The highest ASPRs were found in the High-income Asia Pacific (8.13 per 100,000; 95% UI: 6.69 to 9.98) and East Asia (8.03 per 100,000; 95% UI: 6.35 to 10.35) regions (Table 1 and Fig. 1A). In contrast, Central Latin America (0.40 per 100,000; 95% UI: 0.30 to 0.52) and the Caribbean (0.53 per 100,000; 95% UI: 0.38 to 0.71) reported the lowest ASPRs (Table 1 and Fig. 1A).

Between 1990 and 2021, ASIR trends varied by region. In high and medium-high SDI regions, the ASIR increased modestly by 0.74 per 100,000 (95% UI: 0.64 to 0.84), while low SDI regions saw a notable decline, with the most significant decrease of 1.02 per 100,000 (95% UI: -1.11 to -0.94) (Table 1). Sub-Saharan Africa, for instance, experienced a marked decline, with Central Sub-Saharan Africa showing a decrease of 1.51 per 100,000 (95% UI: -1.62 to -1.40) and Western Sub-Saharan Africa showing a decrease of 1.41 per 100,000 (95% UI: -1.52 to -1.30) (Table 1). East Asia recorded the most significant increase in ASIR, rising by 5.70 per 100,000 (95% UI: 4.49 to 7.29), followed by the High-income Asia Pacific (3.96 per 100,000; 95% UI: 3.23 to 4.84) (Table 1 and Fig. 1B).

Regarding mortality, the middle SDI regions had the highest ASMR at 2.92 per 100,000 (95% UI: 2.35 to 3.64), while the high SDI regions reported the lowest at 1.17 per 100,000 (95% UI: 0.97 to 1.40) (Table 1). The low SDI regions experienced the most significant reduction in ASMR, with a decrease of 1.12 per 100,000 (95% UI: -1.29 to -0.95) (Table 1). East Asia had the highest ASMR at 4.81 per 100,000 (95% UI: 3.78 to 6.13), while Western Sub-Saharan Africa had an ASMR of 3.92 per 100,000 (95% UI: 3.03 to 4.93) (Table 1 and Fig. 1C). In contrast, Australasia and High-income North America saw increases, with ASMRs rising to 2.47 per 100,000 (95% UI: 2.11 to 2.83) and 1.93 per 100,000 (95% UI: 1.65 to 2.21), respectively (Table 1). Similarly, global DALYs followed these trends, with Central Sub-Saharan Africa (-1.49 per 100,000; 95% UI: -1.64 to -1.34) and Western Sub-Saharan Africa (-1.49 per 100,000; 95% UI: -1.64 to -1.34) reporting the most significant declines (Table 1 and Fig. 1D). However, East Asia had the highest DALY burden globally at 155.12 per 100,000 (95% UI: 122.10 to 199.60), followed by Western Sub-Saharan Africa at 118.26 per 100,000 (95% UI: 90.79 to 149.89) (Table 1 and Fig. 1D).

National Trends

Nationally, the ASPR for HBV-LC in 2021 ranged from 0.21 to 21.97 per 100,000 people. The Republic of Korea reported the highest ASPR of 21.97 per 100,000 (95% UI: 17.50 to 27.73), followed by Gambia (18.83 per 100,000; 95% UI: 11.71 to 28.23), Mongolia (18.53 per 100,000; 95% UI: 12.24 to 27.40), and Mali (14.37 per 100,000; 95% UI: 9.65 to 19.77) (Fig. 1A and Supplementary Table S1). In contrast, Morocco (0.21 per 100,000; 95% UI: 0.13 to 0.30) and Argentina (0.27 per 100,000; 95% UI: 0.19 to 0.36) had the lowest ASPRs (Fig. 1A and Supplementary Table S2).

In terms of ASMR, Mongolia (17.18 per 100,000; 95% UI: 11.03 25.21) and Gambia (16.61 per 100,000; 95% UI: 10.32 to 24.97) had the highest rates, while Morocco (0.18/100,000; 95% UI: 0.11 to 0.27) and Sweden (0.22/100,000; 95% UI: 0.16 to 0.31) reported the lowest (Fig. 1C and Supplementary Table S3). A similar trend was observed in the DALYs, with Mongolia and Gambia reporting the highest DALY burdens (Fig. 1D and Supplementary Table S4).

Age and Sex Patterns

In 2021, the global burden of HBV-LC was the highest in the 50–54 age group. However, sex-specific prevalence patterns differed, with males showing the highest prevalence in the 65–69 age group and females in the 85–89 age group (Fig. 2A-B; Supplementary Tables S5). Overall, the prevalence of HBV-LC was significantly higher in males compared than in females. The highest morbidity and mortality rates for both sexes were concentrated in the 85–89 age group, followed by the 80–84 and 90–94 age groups (Fig. 2C-F; Supplementary Tables S6-S7). No HBV-LC cases have been reported in children under ten years. From–20–24 age group onward, the prevalence, morbidity, and mortality progressively increased with age.

Regarding DALYs, males had the highest number of HBV-LC DALYs in the 50–54 age group, with the highest DALY rate in the 65–69 age group. For females, the highest number of DALYs occurred in the 55–59 age group, while the highest DALY rate was in the 65–69 age group. Across all age groups, males consistently exhibited higher DALY rates than females (Fig. 2G-H; Supplementary Tables S8).

Overall Temporal Trends in Gender Structures

From 1990 to 2021, the HBV-LC prevalence, incidence, mortality, and DALY rates showed a modest but consistent increase, followed by a slight decline across all age groups. Prevalence and incidence rates were consistently higher in males than females throughout the study period (Supplementary Fig. 1A-B; Supplementary Tables S9-S10). Between 1990 and 1995, the prevalence and mortality rates increased modestly, followed by a gradual decline, with a minimal decrease from 2015 to 2021. Males consistently had higher incidence, mortality, and DALY rates than females throughout the study period (Supplementary Fig. 1C-D; Supplementary Tables S11-S12). For detailed sex-specific global prevalence data from 1990 to 2021, refer to Supplementary Material.

Temporal Joinpoint Analysis

Joinpoint regression analysis identified age-standardized rate (ASR) trends for HBV-LC prevalence, incidence, mortality, and DALYs from 1990 to 2021. The overall trend in HBV-LC prevalence increased, with an AAPC of 0.18% (95% CI: -0.14% to -0.23%; P < 0.001) (Supplementary Fig. 2A; Supplementary Table S13). The most significant increase occurred between 1996 and 2000 (APC = 2.10%; 95% CI: 1.89–2.30%; P < 0.001), while the sharpest declines were observed between 2000 and 2005 (APC = -1.62%; 95% CI: -1.74% to -1.50%; P < 0.001) and from 2015 to 2021 (APC = -1.12%; 95% CI: -1.21% to -1.02%; P < 0.001).

The ASIR demonstrated an overall decline (AAPC = -0.22%; 95% CI: -0.27% to -0.17%; P < 0.001), with the most pronounced reduction occurring between 2000 and 2005 (APC = -2.19%; 95% CI: -2.33% to -2.06%; P < 0.001) (Supplementary Fig. 2B; Supplementary Table S14). ASMR followed a similar downward trend, with an AAPC of -0.54% (95% CI: -0.81% to -0.27%; P < 0.001). The most substantial decline in ASMR was observed between 2001 and 2005 (APC = -3.12%; 95% CI: -3.91% to -2.31%; P < 0.001), with males contributing significantly to this reduction (Supplementary Fig. 2C; Supplementary Table S15).

Similarly, the DALYs steadily declined from 1990 to 2021 (AAPC = -0.79%; 95% CI: -0.99% to -0.59%; P < 0.001). The most significant reduction in DALYs was observed between 2001 and 2005 (AAPC = -3.79%; 95% CI: -4.36% to -3.22%; P < 0.001) (Supplementary Fig. 2D; Supplementary Table S16).

Changing Patterns at Different SDI Levels and Baseline Burden

SDI, a measure derived from the GBD database, assesses the level of socioeconomic development in a country or region. In 2021, the global burden of HBV-LCs exceeded that expected based on the SDI levels. At the regional level, there was a negative correlation between ASIR and SDI, suggesting that the HBV-LC burden decreases with higher socioeconomic development (Fig. 3).

Interestingly, a "W-shaped" relationship between ASIR and SDI was observed: ASIR gradually decreased when SDI was below 0.4, increased sharply when SDI exceeded 0.7, and fluctuated between 0.4 and 0.7 (Fig. 3A; Supplementary Table S17). A similar pattern was seen for the ASMR, where ASMR steadily decreased when the SDI was below 0.5, increased slightly between 0.5 and 0.55, declined again between 0.55 and 0.75, and then rose sharply in regions with an SDI greater than 0.75 (Fig. 3B; Supplementary Table S18).

At the national level, Mongolia, Mali, South Korea, and Tonga showed significantly higher ASIR values than expected based on their SDI levels (Fig. 3C; Supplementary Table S19). Similarly, ASMR was negatively correlated with SDI, with Mongolia, Mali, Tonga, and Mauritania showing higher-than-expected mortality burdens (Fig. 3D; Supplementary Table S20).

Cross-National Health Inequality in HBV-LC Burden

We calculated the slope index of inequality (SII) for the DALYs to assess the income-related disparities in the burden of HBV-LC. In 1990, the SII for DALYs was − 24.45 (95% CI: -36.15 to -12.74), indicating a significant disparity in the HBV-LC burden, with higher rates in countries with lower SDI values. By 2021, the SII had decreased to -1.87 (95% CI: -18.49 to 14.76), suggesting that while disparities persist, the gap between high-income and low-income countries has narrowed over time (Fig. 4A).

The CI for DALYs also showed a declining trend from 1990 to 2021, indicating a reduction in regional disparities in HBV-LC burden (Fig. 4B). However, global inequality remains a significant challenge, particularly in regions with low SDI values. Although progress has been made in reducing this burden in low-income countries, substantial disparities persist, underscoring the need for targeted interventions to address these inequalities.

Global Disease Burden Projections for HBV-LC (2022–2036)

Using the BAPC model, we projected the global burden of HBV-LC from 2022 to 2036. The model accounts for age, period, and cohort effects and incorporates data from 1990 to 2021. By 2036, the ASIR for HBV-LC is projected to decrease to 3.57 per 100,000 for males and 0.69 per 100,000 for females, representing reductions of 11.9% and 16.9%, respectively, compared with 2021 (Fig. 5A-B; Supplementary Table S21-22).

Similarly, global ASMR is expected to continue declining. By 2036, the ASMR is forecasted to be 5.57 per 100,000 for males and 0.77 per 100,000 for females, reflecting a decrease of 12.6% and 18.9%, respectively, compared to 2021 (Fig. 5C-D; Supplementary Table S23-24). Notably, the decline in HBV-LC morbidity and mortality is expected to be more pronounced among females, contributing significantly to the overall reduction in global HBV-LC burden.

This study comprehensively analyzed the global, regional, and national burden of HBV-LC over 31 years (1990–2021), highlighting significant trends in incidence, mortality, and DALYs. Using advanced statistical models, we projected the future burden of HBV-LCs by 2036, offering valuable insights for policymakers and public health officials. Despite the overall global decline in HBV-LC incidence and mortality rates, our results revealed persistent disparities across regions, age groups, and SDI levels.

Our analysis demonstrated a significant reduction in the global ASIR and ASMR of HBV-LC between 1990 and 2021, with ASIR decreasing by 0.22% annually and ASMR declining by 0.54% annually. This trend reflects the success of widespread HBV vaccination programs and increased access to antiviral therapies, particularly in high-income regions(26, 27). However, despite these advancements, the burden of HBV-LC remains disproportionately high in low- and middle-SDI regions, especially in sub-Saharan Africa and parts of East Asia, where access to healthcare remains limited(28).

Our findings are consistent with previous research showing a decline in liver cancer incidence due to other etiologies, such as hepatitis C virus(11) and non-alcoholic steatohepatitis(10). However, unlike these studies, our analysis provides a more detailed breakdown of the HBV-LC burden, including subgroup analyses by age, sex, and SDI. This granularity is crucial for identifying high-risk populations and for tailoring intervention strategies.

A significant finding of this study was the variation in the HBV-LC burden across different SDI levels. Consistent with the prior literature, we found that regions with lower SDI values, such as Sub-Saharan Africa and South Asia, experience higher HBV-LC mortality(29, 30). Socioeconomic factors, including access to healthcare services, vaccination coverage, and early diagnosis, are critical for shaping health outcomes. In contrast, well-established vaccination programs have significantly reduced the incidence and mortality in high-income regions, such as East Asia and the High-income Asia Pacific.

Interestingly, our study identified a 'W-shaped' relationship between ASIR and SDI, suggesting that regions with both low and very high SDI have an elevated risk of HBV-LC. This finding underscores the complex interplay between socioeconomic development and HBV-related health outcomes. While high-SDI regions benefit from better healthcare infrastructure, lifestyle factors such as increased alcohol consumption may contribute to elevated HBV-LC risk in these populations(31).

The BAPC model used in this study provides robust projections of the HBV-LC burden by 2036. Our forecasts predict continued global declines in ASIR and ASMR by 2036, with reductions of 11.9% and 12.6%, respectively. These trends are primarily driven by improvements in vaccination coverage and antiviral therapies, particularly in middle- and high-income countries. Notably, projections show a more significant reduction in HBV-LC burden among females, suggesting that sex-specific interventions, such as prenatal HBV screening and treatment, could further reduce transmission and liver cancer incidence(32).

Despite these positive trends, the slower decline in low-SDI regions underscores the urgent need for targeted intervention. Expanding access to affordable vaccines, improving healthcare infrastructure, and raising public awareness of HBV prevention are essential strategies for reducing the HBV-LC burden in these areas. Additionally, given the projected slight increase in HBV-LC incidence among females in certain regions, future public health programs should incorporate gender-sensitive approaches(12).

While this study offers valuable insights into the global HBV-LC burden, it has some limitations. The accuracy of our projections depends on the quality and availability of underlying data, which may vary across regions. Additionally, while the GBD database provides comprehensive estimates, underreporting or misclassification of HBV LC cases may occur, particularly in resource-limited settings. Furthermore, the impact of emerging treatments, such as new antiviral drugs and immunotherapies, on the future HBV-LC burden was not fully considered in this analysis. Future studies should evaluate the long-term effects of these treatments on HBV-related outcomes.

In conclusion, this study highlights the ongoing global challenge posed by HBV-related liver cancer, particularly in low-SDI regions, where healthcare access is limited. Significant disparities persist, and progress has been made in reducing the overall burden. Continued efforts to expand vaccination programs, improve early diagnosis, and ensure equitable access to antiviral therapies are essential for achieving the World Health Organization's goal of eliminating HBV as a public health threat by 2030.

This study provides the most comprehensive analysis of the global, regional, and national burden of HBV-LC from 1990 to 2021. Despite significant progress in reducing the incidence and mortality of HBV-LC globally, substantial disparities persist across socio-demographic and regional lines. The findings highlight the ongoing challenge of HBV-LC, particularly in low-SDI regions where healthcare access and vaccination coverage remain inadequate. Our projections indicate that the global burden of HBV-LC will continue to decline through 2036, driven by improvements in vaccination programs and antiviral therapies. However, the slower progress in low- and middle-income regions emphasizes the need for targeted interventions, including expanding access to affordable healthcare, enhancing early diagnostic services, and increasing public awareness.

These results underscore the importance of sustained global efforts to eliminate HBV as a public health threat. By addressing the persistent disparities in HBV-LC burden, particularly in regions with the highest unmet needs, global health initiatives can further reduce morbidity and mortality, moving closer to achieving WHO’s 2030 goals. Future research should focus on evaluating the impact of emerging therapies and exploring gender-specific interventions to enhance the effectiveness of HBV control strategies worldwide.

HBV

Hepatitis B virus

HBV-LC

Hepatitis B virus-related liver cancer

WHO

The World Health Organization

GBD

Global Burden of Disease

IHME

Institute for Health Metrics and Evaluation

DALYs

Disability-adjusted life years

SDI

Socio-demographic index

APC

Annual percent change

AAPC

Average annual percent change

Concentration index

UIs

Uncertainty intervals

SII

Slope index of inequality

RII

Relative inequality index

ASR

Age-standardized rate

ASPR

Age-standardized prevalence rate

ASIR

Age-standardized incidence rate

ASMR

Age-standardized mortality rate

BAPC

Bayesian age-period-cohort

Acknowledgements

We thank the Institute of Health Metrology and Evaluation for sharing valuable GBD data.

Authors’ contributions

DJ W, ZW G and J L had full access to all data in the study and took responsibility for the integrity of the data and the accuracy of the data analysis. YP L and WL L planned the concept of this study. L W, L Y, RH M conducted data extraction and analysis. DJ W, ZW G, Y L, L W and RH M carried out data cleaning and material support. All authors critically reviewed, revised and contributed to the final manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

Funding

This study was supported by Scientific and technological innovation project of China Academy of Chinese Medical Sciences (No.CI2021A00801 、No.CI2021A00806 and No.CI2023C026YL) and Sanming Proiect of Medicine in Shenzhen (No.SZZYSM202311014).

Availability of data and materials

Availability of data and materials: Relevant data can be retrieved through the available website ( https://vizhub.healthdata.org/gbd-results/ ).

Ethics approval and ethics approval and consent to participate

For the GBD, which is publicly available, and no identifiable information was included in the analyses, the ‘Ethical approval and Ethics Approval and Consent to Participate’ was not applicable.

Consent for Publication

All participants in this study consented to publication.

Competing interests

The authors declare that they have no competing interests.

Author details

¹Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, China;

²Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China;

³Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100053, China

⁴Department of Laboratory, Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, 100053, China

⁵Department of Hepatology, Shenzhen Bao'an District Traditional Chinese Medicine Hospital, Shenzhen, 518100, China.

Collaborators GBDHB. Global, regional, and national burden of hepatitis B, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Gastroenterol Hepatol. 2022;7(9):796–829.
Collaborators GBDRF. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1223–49.
Gines P, Krag A, Abraldes JG, Sola E, Fabrellas N, Kamath PS. Liver cirrhosis. Lancet. 2021;398(10308):1359–76.
Vogel A, Meyer T, Sapisochin G, Salem R, Saborowski A. Hepatocellular carcinoma. Lancet. 2022;400(10360):1345–62.
Liu Y, Zheng J, Hao J, Wang RR, Liu X, Gu P, et al. Global burden of primary liver cancer by five etiologies and global prediction by 2035 based on global burden of disease study 2019. Cancer Med. 2022;11(5):1310–23.
Collaborators GBDCRF. The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2022;400(10352):563–91.
The L. Eliminating viral hepatitis: time to match visions with action. Lancet. 2017;390(10108):2121.
Cao G, Jing W, Liu J, Liu M. Countdown on hepatitis B elimination by 2030: the global burden of liver disease related to hepatitis B and association with socioeconomic status. Hepatol Int. 2022;16(6):1282–96.
Hatzakis A, Lazarus JV, Cholongitas E, Baptista-Leite R, Boucher C, Busoi CS, et al. Securing sustainable funding for viral hepatitis elimination plans. Liver Int. 2020;40(2):260–70.
Pang J, Chen K, Chen S, Chen X. Global burden of nonalcoholic steatohepatitis-related liver cancer, 1990–2019: a systematic analysis for the GBD 2019. Diabetol Metab Syndr. 2022;14(1):112.
Wei J, Ouyang G, Huang G, Wang Y, Li S, Liu J, et al. Burden of liver cancer due to hepatitis C from 1990 to 2019 at the global, regional, and national levels. Front Oncol. 2023;13:1218901.
Liu Y, Sun Z, Wang Q, Wu K, Tang Z, Zhang B. Contribution of alcohol use to the global burden of cirrhosis and liver cancer from 1990 to 2019 and projections to 2044. Hepatol Int. 2023;17(4):1028–44.
Diseases GBD, Injuries C. Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):2133–61.
Tuo Y, Li Y, Li Y, Ma J, Yang X, Wu S, et al. Global, regional, and national burden of thalassemia, 1990–2021: a systematic analysis for the global burden of disease study 2021. EClinicalMedicine. 2024;72:102619.
Infections GBDLR, Antimicrobial Resistance C. Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990–2021: a systematic analysis from the Global Burden of Disease Study 2021. Lancet Infect Dis. 2024;24(9):974–1002.
Wang F, Ma B, Ma Q, Liu X. Global, regional, and national burden of inguinal, femoral, and abdominal hernias: a systematic analysis of prevalence, incidence, deaths, and DALYs with projections to 2030. Int J Surg. 2024;110(4):1951–67.
Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000;19(3):335–51.
Clegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK. Estimating average annual per cent change in trend analysis. Stat Med. 2009;28(29):3670–82.
Hosseinpoor AR, Bergen N, Schlotheuber A. Promoting health equity: WHO health inequality monitoring at global and national levels. Glob Health Action. 2015;8:29034.
Lu M, Li D, Hu Y, Zhang L, Li Y, Zhang Z, et al. Persistence of severe global inequalities in the burden of Hypertension Heart Disease from 1990 to 2019: findings from the global burden of disease study 2019. BMC Public Health. 2024;24(1):110.
Lin Y, Jiang B, Cai Y, Luo W, Zhu X, Lin Q et al. The Global Burden of Glaucoma: Findings from the Global Burden of Disease 2019 Study and Predictions by Bayesian Age-Period-Cohort Analysis. J Clin Med. 2023;12(5).
Riebler A, Held L. Projecting the future burden of cancer: Bayesian age-period-cohort analysis with integrated nested Laplace approximations. Biom J. 2017;59(3):531–49.
Knoll M, Furkel J, Debus J, Abdollahi A, Karch A, Stock C. An R package for an integrated evaluation of statistical approaches to cancer incidence projection. BMC Med Res Methodol. 2020;20(1):257.
Diseases GBD, Injuries C. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396(10258):1204–22.
Sun P, Yu C, Yin L, Chen Y, Sun Z, Zhang T, et al. Global, regional, and national burden of female cancers in women of child-bearing age, 1990–2021: analysis of data from the global burden of disease study 2021. EClinicalMedicine. 2024;74:102713.
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).
Li W, Deng R, Liu S, Wang K, Sun J. Hepatitis B virus-related hepatocellular carcinoma in the era of antiviral therapy: The emerging role of non-viral risk factors. Liver Int. 2020;40(10):2316–25.
Amponsah-Dacosta E. Hepatitis B virus infection and hepatocellular carcinoma in sub-Saharan Africa: Implications for elimination of viral hepatitis by 2030? World J Gastroenterol. 2021;27(36):6025–38.
Bray F, Parkin DM, African Cancer Registry N. Cancer in sub-Saharan Africa in 2020: a review of current estimates of the national burden, data gaps, and future needs. Lancet Oncol. 2022;23(6):719–28.
Ou TY, Huy LD, Mayne J, Shih CL, Mai Xuan H, Thi Hong Nguyen N, et al. Global mortality of chronic liver diseases attributable to Hepatitis B virus and Hepatitis C virus infections from 1990 to 2019 and projections to 2030. J Infect Public Health. 2024;17(7):102443.
Cao G, Liu J, Liu M, Global. Regional, and National Trends in Incidence and Mortality of Primary Liver Cancer and Its Underlying Etiologies from 1990 to 2019: Results from the Global Burden of Disease Study 2019. J Epidemiol Glob Health. 2023;13(2):344–60.
Lu QB, Cui F. Preventing mother-to-child transmission of HBV. Lancet Infect Dis. 2022;22(8):1096–7.

Table 1 is available in the Supplementary Files section.

No competing interests reported.

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Global, regional, and national health inequalities in hepatitis B virus-related liver cancer in 204 countries, 1990-2021

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Abstract

Background

Objective

Methods

Results

Conclusion

Figures

Introduction

Methods

Data Acquisition and Sources

Joinpoint Regression Model

Measurement Health Inequalities

Bayesian Age-Period-Cohort (BAPC) Model Prediction

Statistical Analysis

Results

Global Trends

Regional Trends

National Trends

Age and Sex Patterns

Overall Temporal Trends in Gender Structures

Temporal Joinpoint Analysis

Changing Patterns at Different SDI Levels and Baseline Burden

Cross-National Health Inequality in HBV-LC Burden

Global Disease Burden Projections for HBV-LC (2022–2036)

Discussion

Conclusion

Abbreviations

Declarations

References

Table 1

Additional Declarations

Supplementary Files

Status:

Version 1