Trends in global early-onset liver cancer from 1990 to 2050: an analysis of the Global Burden of Disease Study 2021

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This study aims to assess health inequalities in EOLC burden across regions and sexes and to inform targeted interventions. Methods: Using Global Burden of Disease (GBD) 2021 data, we analyzed global EOLC incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. Analyses included Joinpoint regression, decomposition, locally estimated scatterplot smoothing (LOESS), and frontier efficiency assessment. Trends to 2050 were projected via a gender-stratified Bayesian age-period-cohort (BAPC) model. Results: Absolute EOLC burden increased globally, though age-standardized rates (ASRs) declined overall. Notably, age-standardized incidence rates (ASIRs) rose among women in high socio-demographic index (SDI) regions and among men in low-middle SDI regions. Hepatitis B virus (HBV) remained the leading cause, but alcohol, hepatitis C virus (HCV), and nonalcoholic steatohepatitis (NASH), especially in young women, showed increasing contributions. Population growth and aging drove increases in the absolute burden. Frontier analysis identified Mongolia as the lowest-performing country, while Somalia, Burundi, and Ethiopia achieved relatively efficient control. The BAPC model projects continued ASR declines by 2050, yet female ASIR is expected to rise modestly due to rising NASH. Conclusion: Despite an overall declining EOLC burden, persistent gender and regional inequities and the growing impact of metabolic risks like NASH call for precision public health approaches, including etiology-specific strategies, early screening for high-risk groups (particularly young women), and strengthened health systems in underperforming regions. Early-onset liver cancer Global burden of disease study Incidence Mortality Disability adjusted life years Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1 Introduction According to GLOBOCAN 2022, liver cancer (LC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide [1]. Hepatocellular carcinoma (HCC), which accounts for 75-85% of primary LC cases, followed by intrahepatic cholangiocarcinoma (ICC, 10-15%) and other rare types. Major risk factors include chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, exposure to carcinogens, metabolic dysfunction, and genetic predisposition [2]. Although HBV vaccination and antiviral therapy have reduced the incidence of virus-associated LC, the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease (ALD) is driving an increasing global burden of LC [3]. With advances in cancer screening, the proportion of early-onset cancers, diagnosed before age 50, has increased in many countries, possibly reflecting cumulative early life exposure to adverse environments or lifestyles [4]. Emerging evidence has compared early-onset cancer (EOLC) and late-onset cancer (LOLC) in terms of etiology, clinical manifestations, tumor biology, and outcomes. Beyond viral hepatitis, metabolic disorders and alcohol abuse are key contributors to EOLC [5]. EOLC often presents with less cirrhosis, leading to delayed or missed diagnosis. In addition, EOLC usually exhibits more aggressive biological features, including high-grade histology, metastasis, or lymph node involvement, which may lead to a worse prognosis. However, early detection and timely intervention can significantly improve outcomes for EOLC patients compared to LOLC patients, underscoring the need to extend screening to younger, high-risk populations [6–8]. Research shows that while the absolute burden of EOLC increased from 1990 to 2021 globally, the age-standardized rates (ASRs) of incidence, mortality, and disability adjusted life year (DALY) have decreased slightly [9]. Besides, Significant geographic heterogeneity persists, with DALYs attributable to metabolic risks rising markedly, especially among young adults with both HBV and obesity [10]. Furthermore, GLOBOCAN 2022 reports a notable increase in EOLC incidence in Northern Europe, driven largely by rising ICC rates, particularly among women in North America, Western Europe, Australia, and New Zealand [11]. This study leverages the Global Burden of Disease (GBD) 2021 data to comprehensively assess the EOLC burden from 1990 to 2021, characterize its spatiotemporal patterns, and project trends through 2050. Building on prior work, our analysis incorporates stratification, decomposition, and efficiency frontier methods to identify key drivers and dynamic shifts in disease burden, providing robust evidence to inform targeted prevention and control strategies for at-risk populations. 2 Materials and Methods 2.1 Data source GBD 2021 provides comprehensive estimates of the epidemiological burden for 371 diseases and injuries, along with 88 key risk factors, across 204 countries and territories. It employs an integrated modeling framework that synthesizes data from national health systems, disease surveillance, cancer registries, population-based surveys, and peer-reviewed literature [12]. Using the Global Health Data Exchange (GHDx) query tool (https://ghdx.healthdata.org/gbd-2021), we extracted age-specific burden estimates for early-onset liver cancer (EOLC) among individuals aged 15–49 years from 1990 to 2021, focusing on incidence, mortality, and DALYs. 2.2 Data Processing Age-standardized rates and their 95% uncertainty intervals (UIs) for individuals aged 15–49 years were calculated using the GBD world population age-standard weights and age-specific rates across seven 5-year age groups (15–19 to 45–49 years). 2.3 Data Analysis We compared the global burden of EOLC between 1990 and 2021, stratifying by sex, age, etiology, and region. Joinpoint regression was used to estimate the annual percent change (APC), average annual percent change (AAPC), and 95% confidence intervals (CIs), capturing both short-term fluctuations and long-term trends. Decomposition analysis attributed changes in disease burden to population growth, aging, and epidemiological shifts. To assess the relationship between EOLC burden and socioeconomic development, we plotted ASRs against the Socio-demographic Index (SDI) for 204 countries in 2021, fitting a LOESS curve. An SDI-efficiency frontier, constructed via bootstrap resampling and cumulative minimum methods, identified countries with high or low performance in burden control relative to their SDI. Finally, using GBD data, we applied a Bayesian age-period-cohort (BAPC) model to project global age-standardized incidence, mortality, and DALY rates for individuals aged 15–49 years from 2022 to 2050, with separate models by sex. As this study used anonymized data from publicly available sources, institutional ethical approval and informed consent were not required. 3 Results 3.1 Global burden of EOLC from 1990 to 2021 Table 1 and Table S1 summarize the global burden of EOLC in 1990 and 2021, and detail absolute numbers, ASRs, and AAPCs of incidence, deaths, DALYs by region and sex. Fig 1 visually illustrates the spatial distribution of EOLC across 204 countries and territories in 1990 and 2021. In 2021, EOLC accounted for approximately 74,948 new cases (95% UI: 65,248–87,630), 58,825 deaths (95% UI: 51,340–68,518), and 2,889,492 DALYs (95% UI: 2,528,098–3,356,476) globally, marking a substantial increase in absolute burden since 1990. However, ASRs declined over the same period, indicating reduced risk after adjusting for population structure. The age-standardized incidence rate (ASIR) decreased from 2.2 to 1.8 per 100,000, the mortality rate (ASMR) from 2.0 to 1.4 per 100,000, and the DALY rate (ASDR) from 97.3 to 70.5 per 100,000. Corresponding average annual percent changes (AAPCs) were −0.609 for ASIR, −0.973 for ASMR, and −1.008 for ASDR (all P < 0.05), reflecting consistent long-term declines. In 2021, the burden of EOLC was markedly higher in males than in females, with 59,037 cases (ASIR: 2.8 per 100,000), 45,930 deaths (ASMR: 2.2 per 100,000), and 2,241,536 DALYs (ASDR: 108.4 per 100,000). Despite this disparity, ASRs declined more rapidly in females than in males. Female AAPCs were −0.712 for ASIR, −1.009 for ASMR, and −1.024 for ASDR, compared to −0.565, −0.928, and −0.971 in males, respectively (all 95% CIs excluding zero). In 2021, the highest age-standardized rates (ASRs) were observed in the middle SDI region (ASIR: 2.4, ASMR: 1.9, ASDR: 91.7 per 100,000), while the high SDI region had the lowest ASMR (0.7) and ASDR (35.2). From 1990 to 2021, ASRs generally declined across most SDI groups, with the steepest reductions in the middle SDI region. Notable exceptions were rising ASIRs among women in high SDI countries (AAPC = 0.423) and men in low-middle SDI countries (AAPC = 0.139). Among WHO regions, the Western Pacific bore the highest EOLC burden in 2021, with an ASIR of 4.1, ASMR of 3.0, and ASDR of 146.7 per 100,000. From 1990 to 2021, ASIR significantly declined in the African, Eastern Mediterranean, and Western Pacific regions (AAPC < 0, P 0, P 0). In terms of the number of incidences, deaths, and DALYs, China, India, and Vietnam were the top three countries with the highest absolute burden in the world. In terms of incidence, China (50232; 95% UI: 38509-61051) was far higher than India (6105, 95% UI: 5134-7373) and Vietnam (3200, 95% UI: 2038-4373), making it the country with the heaviest absolute burden. In terms of deaths, China was also significantly higher than the other two countries, ranking first (36519, 95% UI: 28127-44788). China had the heaviest burden of DALYs (1769074, 95% UI: 1363072-2175076), followed by India (277039, 95% UI: 232488-321590), and Vietnam (131652, 95% UI: 85041-178263). In 2021, Mongolia, Gambia, and Eswatini had the highest ASIR (12.9, 95% UI: 8.4-19.2; 12.3, 95% UI: 6-22.9; 8.6, 95% UI: 2.3-23.1, respectively). Their ASMR was also the highest (12.0, 95% UI: 7.9-17.8; 11.4, 95%UI：5.6-21.1; 8.0, 95% UI: 2.1-21.3, respectively). Similarly, the top three countries in ASDR were Mongolia (569.5, 95% UI: 372.2-841.8), Gambia (546.2, 95% UI: 269.2-1016.5), and Eswatini (389.6, 95% UI: 103.7-1047.3). Between 1990 and 2021, the ASIR of EOLC in Mongolia slightly decreased, but it was statistically significant (AAPC=-0.168, 95% CI: -0.272 to -0.065). In contrast, the decline trends of ASMR and ASDR were not statistically significant. On the contrary, the incidence rate of Gambia and Eswatini shows an upward trend: the APCC of ASIR for Gambia ASIR was 0.345 (95% CI: 0.148-0.543), while that of ASIR for Eswatini rises sharply to 3.593 (95% CI: 3.300-3.886). In addition, Eswatini also increased significantly in ASMR (AAPC=3.618, 95% CI: 3.332-3.905) and ASDR (AAPC=3.627, 95% CI: 3.323-3.931). Fig 2A, 2D, and 2E show gender-specific temporal trends of ASRs in EOLC. Among men, ASIR increased from 1990 to 2000, decreased from 2001 to 2005, slightly increased from 2006 to 2013, and gradually decreased after 2014. Among women, ASIR slowly increased from 1990 to 2000, then steadily decreased until there was less fluctuation after 2006. Similar patterns were observed in ASMR and ASDR. Fig 2B, 2E, and 2H present the ASR trends of EOLC across different SDI levels. In low SDI regions, ASRs began to decline after 1996. High SDI regions initially increased, but then continued to decline from around 2000. Middle SDI regions experienced a sharp decline after 2000, rebounded slightly after 2006, and gradually declined from 2016 onwards. Fig 2C, 2F, and 2I show Joinpoint regression results of ASRs in WHO regions. In the Western Pacific and African regions, ASRs have shifted from an upward trend to a downward trend since 2001, and have further declined since 2006. They have been on a downward trend since 2010. In contrast, ASRs in the Eastern Mediterranean, European, American, and Southeast Asian regions only showed slight fluctuations over time. As shown in Fig 3A, the incidence rate, mortality, and DALYs related to EOLC gradually increase with age, and men always bear a higher burden than women. Fig S1-S3 further illustrate that the burden of EOLC varies by gender, region, and underlying etiology in different age groups, but typically shows an upward trend, especially in men, the growth of the elderly is more rapid. The absolute burden of cancer caused by NASH and others is higher in females aged 15-29 than in males of the same age group (Fig S3). Fig 3B shows the changes in the etiological composition of the total burden between 1990 and 2021. In 1990, HBV accounted for the majority of cases (71.8%), followed by HCV (8.9%), alcohol consumption (8.8%), and non-alcoholic steatohepatitis (NASH) (4.3%). By 2021, HBV remained the main cause (67.9%), although its relative contribution has slightly decreased. During the same period, the proportion of cases caused by HCV increased to 9.5%, the proportion of cases related to alcohol slightly increased to 11.1%, and the proportion of cases related to NASH increased to 5.7%. The mortality rate also showed a similar pattern: the proportion of deaths caused by HBV decreased from 72.3% to 67.4%, while alcohol-related deaths increased from 8.6% to 11.2%, HCV-related deaths increased from 8.6% to 9.6%, and NASH-related deaths increased from 4.3% to 6%. DALYs also showed a similar trend, with HBV still dominating (72.8% in 1990 and 67.7% in 2021), and alcohol, HCV, and NASH contributing increasingly. Fig S4 shows that alcohol, HCV, and NASH are increasingly contributing to carcinogenesis in both males and females, in addition to HBV. However, from 1990 to 2021, the proportion of LC caused by alcohol increased significantly in males, while the proportion of LC caused by HCV and NASH increased significantly in females. Fig 3C illustrates the distribution of the etiologies of EOLC in different age groups. Overall, HBV remained the main cause. It was worth noting that as age increased, the relative contribution rate of NASH decreased, while the proportion of HCV and alcohol consumption increased accordingly. Decomposition analysis of burden of EOLC in different regions Decomposition analysis revealed that the increase in the incidence rate of EOLC was mainly driven by population growth and aging. Although the epidemiological component was negative, indicating that ASIR actually declined. The population pressure exceeded this positive trend. The changes in mortality were similar. Although epidemiological factors suggest that the risk of death may decrease (negative ASMR), the total number of deaths has increased, mainly due to population growth and aging. Likewise, DALYs have also increased. Although epidemiological factors remained negative (negative ASDR), they were still insufficient to offset the significant impact of population growth and aging (Fig 4A). Across WHO regions, the incidence rate of early-onset cancer in the Western Pacific region has increased the most, mainly due to the aging of the population. Although the epidemiological factors were negative, reflecting the decline in incidence, this favorable trend was offset by population pressures. The South-East Asia region has the highest absolute numbers of deaths and DALYs, followed by the African region. The rapid population growth was the dominant driver of the rising burden. In contrast, the net changes in the Americas, Europe, and the Eastern Mediterranean regions are relatively small, showing a slight overall increase. It is worth noting that the epidemiological factors in Americas and Europe are slightly positive (Fig 4B). The increase in EOLC cases and deaths in low SDI and low-middle SDI regions was mainly attributed to population growth, resulting in a continued increase in the overall burden. On the contrary, in high SDI and middle-high SDI regions, epidemiological factors remained negative, indicating a decrease in DALYs and a relatively low overall burden (Fig 4C). 3.2 The relationship between the burden of EOLC and SDI Fig 5A, 5D, and 5E show that in 204 countries and territories. The ASIR, ASMR, and ASDR of EOLC generally decrease with the increase of SDI, and the trend tends to be flat and slightly increased. Overall, countries and territories with higher SDI categories had maintained relatively low tumor burden. It was worth noting that Mongolia, Gambia, and Eswatini significantly deviated from the LOESS curve, reflecting a significant increase in the burden that cannot be explained by SDI alone. The frontier analysis of the relationship between the SDI and ASRs of ELOC in 204 countries and territories from 1990 to 2021 revealed a general reverse association. ASIR, ASMR, and ASDR tended to decrease and concentrate with the increasing SDI (Fig 5B, 5E, and 5H). Besides, the frontier analysis evaluated national performance in 2021 by comparing the observed tumor burden with the optimal level achievable by SDI of each country. For ASIR, the ASIR of 15 countries, including Mongolia, Gambia, and Eswatini, increased significantly, far below the frontier, indicating their serious disease burden. In contrast, Somalia, Burundi, Ethiopia, Yemen, Haiti, and other low SDI countries were closer to the frontier, which showed that their limited socio-economic resources were relatively effective in preventing and controlling EOLC. Compared to their level of development, this poor performance highlighted the need for increased attention to the emerging or persistent burden of EOLC in other high-resource environments (Fig 5C, 5F, and 5I). 3.3 Global burden of EOLC from 2021 to 2050 predicted by the BAPC model From 1990 to 2020, ASRs of EOLC, including ASIR, ASMR, and ASDR, followed a consistent time pattern in the overall, male, and female population: initially increasing, then decreasing, and finally stabilizing at a relatively stable or slightly lower stable period around 2020. Since 2020, the overall ASIR has been declining year by year, with men experiencing a greater decline, while women have experienced moderate but stable annual growth (Fig 6A-6C). The forecast by 2050 indicates that the overall ASIR will decrease to 1.577 new cases per 100,000 population (95% UI: 1.57677-1.57684). It is expected that the ASIR of males will significantly decrease to 2.063 (95% UI: 2.06287-2.06296), while the ASIR of females will slightly increase to 0.880 (95% UI: 0.87990-0.87993), consistently lower than males and only showing a mild upward trend. The specific values of ASRs are shown in Tables S2-S4. Similarly, the overall ASMR is expected to decrease to 1.206 deaths per 100,000 population (95% UI: 1.20599-1.20605), mainly due to a larger decline in male ASMR (1.533; 95% UI: 1.53338-1.53347), while female ASMR will slightly increase to 0.696 (95% UI: 0.69590-0.69592). For ASDR, the overall incidence rate is expected to decline to 61.89 cases per 100,000 population (95% UI: 61.8860-61.88904), male ASDR will decline significantly to 79.87 (95% UI: 79.86857-79.87270), and female ASDR will rise slightly to 36.56 (95% II: 36.55914-36.56051). Although ASMR and ASDR in women are expected to increase moderately, their absolute burden is still relatively low, and the magnitude of the increase is limited. 4 Discussions Unlike previous studies [10,13], this study used the BAPC model to project EOLC trends to 2050 based on the GBD 2021 dataset, integrating various methods such as joint point regression, decomposition analysis, LOESS, and frontier analysis. E EOLC primarily affects middle-aged individuals, with risk rising with age and peaking at 45–59 years, underscoring its strong link to aging [14]. In 2021, the global absolute burden of EOLC increased, with men bearing a significantly higher burden than women. Although women had a slightly higher AAPC, men exhibited a substantially greater APC, a disparity likely attributable not only to biological factors (e.g., sex hormones) but also to gender differences in exposure to modifiable environmental and behavioral risk factors [15,16]. Globally, ASRs, particularly ASMR and ASDR, rose until around 2000 before declining significantly, likely due to widespread hepatitis B vaccination and antiviral therapy introduced in the 1990s [17,18]. This trend is similar to the global epidemiological changes in overall LC [19]. Due to data limitations, this study was unable to assess epidemiological trends by liver cancer subtype. SEER data indicated that from 2010 to 2019, the incidence rate of early-onset HCC declined (APC was − 4.67%), while the incidence rate of early-onset ICC increased (APC was+8.12%)[20]. Geographically, the highest EOLC burden remains in middle, high-middle SDI, and Western Pacific regions, although their ASRs have gradually declined, reflecting progress toward the WHO’s goal to eliminate hepatitis B by 2030 [18]. In contrast, rising ASIRs have been observed among males in low-middle SDI regions, females in high SDI regions, and populations in Europe and the Americas, primarily driven by increasing NASH [21,22]. In high SDI regions, the rise in female incidence may stem not only from improved screening and HBV control but also from growing contributions of HCV, NASH, and alcohol use [3]. These changes highlight the urgent need for targeted early detection strategies for emerging high-risk groups. In addition, for different races/ethnicities in different regions, it is also necessary to pay attention to the influence of other factors, such as comorbidities [23]. Etiological analysis reveals a shifting global etiology profile of EOLC. Although the relative contribution of HBV has slightly decreased, HBV-related LC remains dominant, accounting for over 60% of cases, predominantly in males. Despite widespread vaccination, the large reservoir of chronic HBV infections and long-term latency of disease ensure its continued substantial contribution to the cancer burden in the coming years. Sustained efforts to vaccinate newborns and expand access to antiviral treatment for adults remain critical, requiring at least a 2% annual decrease in ASIR to effectively curb burden growth [24]. In addition, Viral hepatitis is more prevalent in low- and middle-income countries, while alcohol use and obesity are more common in high-income countries [25]. ALD has become the second leading cause of EOLC, with its attributable fraction steadily rising, especially among males, underscoring the urgent need for stricter alcohol control policies and targeted public health interventions [26]. HCV ranks third. Its contribution among women has significantly increased in recent years. Given the availability of highly effective antiviral therapies, HCV-related LC is now largely preventable and curable, and further expanding screening and treatment coverage could substantially reduce this burden [27,28]. NASH is the fourth leading cause, showing a moderate but sustained increase, especially in populations with high body mass index and fasting blood glucose, likely driven by the global rise in obesity and metabolic syndrome [29,30]. As risk factors prevalent among young people, NASH and alcohol will become the main non-communicable drivers of cancer burden in the coming decades [29,31]. This study did not include data on EOLC burden in children and therefore did not assess hepatoblastoma. A study has reported declining overall incidence and mortality of hepatoblastoma, alongside a rising proportion of liver cancer cases attributable to NASH and alcohol [32]. Although traditional infectious causes of EOLC have been effectively controlled, emerging metabolic and behavioral risk factors are rapidly filling the epidemiological gap [12]. Curbing the rising burden of EOLC requires shifting from single-target antiviral strategies to a comprehensive, multifactorial approach through enhanced early detection, risk-stratified interventions, and cross-sectoral public health collaboration. Decomposition analysis shows that, despite a rising absolute burden, the ASR of EOLC has declined, indicating reduced underlying epidemiological severity after adjusting for population growth and aging, and reflecting the success of current prevention efforts. China and India have a relatively high absolute disease burden due to their population base. Moreover, data from GLOBOCAN 2020 and GBD 2019 indicated that the burden is increasing with global population aging and ranked as the fifth leading cause of cancer-related death worldwide (ASMR = 47.7%) [33]. The high prevalence of comorbidities in older adults, particularly cardiovascular disease, diabetes, and chronic respiratory diseases, complicates clinical management, heightens care demands, and imposes substantial socioeconomic strain [34,35]. Strengthening comprehensive prevention and control strategies is therefore essential to further reduce the LOLC burden and address the complex health needs of aging populations. Efficiency frontier analysis identifies five low-SDI countries, Somalia, Burundi, Ethiopia, Haiti, and Yemen, as closest to the optimal EOLC prevention and control frontier. Despite limited resources, their relatively strong performance warrants an in-depth study of context-specific strategies that may offer scalable lessons. In contrast, Mongolia, The Gambia, and Eswatini lie furthest from the frontier, reflecting both a high EOLC burden and suboptimal control outcomes. These countries urgently require tailored public health responses aligned with local epidemiology, including enhanced early screening, targeted etiological interventions (e.g., antiviral therapy, alcohol and metabolic risk management), and strengthened healthcare infrastructure to improve overall cancer prevention and control capacity [36,37]. The BAPC model predicts a continued decline in the overall ASR of EOLC over the next 29 years, with the notable exception of women, whose burden may rise. Our findings indicate that NASH is becoming increasingly common among young women, with a relatively high proportion among adolescents aged 15-29, which may be a key factor in this trend, especially among women. An analysis of GBD 2021 indicated that the global burden of NAFLD continues to rise, with high-risk populations mainly consisting of youth, middle-aged men, and older women [38]. Future EOLC prevention strategies must address gender and regional health inequities through targeted interventions to mitigate emerging risk factors like NASH and ensure equitable progress in global cancer control. This study has several limitations. Firstly, due to differences in disease surveillance systems, diagnostic capabilities, and reporting standards across regions, EOLC data exhibits heterogeneity in source and quality, which may lead to incomplete or inaccurate data, thereby introducing reporting bias and affecting the estimation of true disease burden. Secondly, this study did not include pathological subtyping information of liver cancer, making it impossible to further evaluate the burden of different subtypes. Finally, although future trend predictions are based on strict BAPC models, they may still be affected by unforeseeable factors in the future, such as adjustments in public health policies, the emergence of new risk factors, socio-economic changes, or advances in medical technology, which can deviate from the predicted trajectory. Therefore, although this study provides valuable evidence for the spatiotemporal heterogeneity of global EOLC, the interpretation of the results still needs to be cautious, and localized analysis and application should be combined with specific social, economic, and health backgrounds in each region. 5 Conclusion Our study elucidates the epidemiology and future trends of EOLC, revealing an overall declining disease burden but persistent disparities by gender and region. These findings underscore the need to shift from broad prevention toward equitable, precision-focused strategies, particularly through enhanced etiological research, early screening in high-risk women, and targeted interventions against emerging risk factors. Prioritizing high-burden and underperforming regions is essential to achieving fair and sustainable global EOLC control. Abbreviations LC Liver cancer HCC Hepatocellular carcinoma ICC Intrahepatic cholangiocarcinoma HBV Hepatitis B virus HCV Hepatitis C virus MASLD Metabolic dysfunction-associated steatotic liver disease ALD Alcoholic liver disease EOLC Early-onset liver cancer LOLC Late-onset liver cancer ASR Age-standardized rate ASIR Age-standardized incidence rate ASMR Age-standardized mortality rate ASDR Age-standardized disability-adjusted life year rate DALY Disability-adjusted life year UI Uncertainty interval CI Confidence interval APC Annual percent change AAPC Average annual percent change SDI Socio-demographic Index LOESS Locally estimated scatterplot smoothing GHDx Global Health Data Exchange GBD Global Burden of Disease BAPC Bayesian age-period-cohort WHO World Health Organization NAFLD Nonalcoholic fatty liver disease NASH Nonalcoholic steatohepatitis Declarations Acknowledgments We thank the GBD Study collaborators for their work. Funding Not applicable. Author contributions Yaoge Liu, Junwei Zhang, and Xin Lu contributed to the study conception and design. Material preparation, data collection and analysis were performed by Zhihong Chen and Han Zheng, Shunan Zhou, Shenao Zhang, Yunhan Mao, and Yiyao Xu. The first draft of the manuscript was written by Zhihong Chen and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Competing interests The authors declare no competing interests. Ethical Approval and accordance Not applicable. Consent to publish Not applicable. Consent to participate Not applicable. Data availability The datasets generated during the current study are available in the GBD database (https://gbd2021.healthdata.org/gbd-results/). References Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 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The number, ASR and AAPC of early-onset liver cancer by global, SDI regions, WHO regions in 2021 Location Sex Incidence Deaths DALYs Number (95%UI) ASR (95%UI) AAPC (95%CI) Number (95%UI) ASR (95%UI) AAPC (95%CI) Number (95%UI) ASR (95%UI) AAPC (95%CI) Global Male 59037 (49998-72069) 2.8 (2.4-3.5) -0.565 (-0.64 - -0.49) 45930 (38909-55822) 2.2 (1.8-2.7) -0.928 (-1.132 - -0.722) 2241536 (1901989-2722915) 108.4 (90.6-132.2) -0.971 (-1.17 - -0.772) Female 15911 (14229-17834) 0.8 (0.7-0.9) -0.712 (-0.754 - -0.67) 12896 (11582-14375) 0.6 (0.6-0.7) -1.009 (-1.16 - -0.857) 647956 (582243-722083) 32.1 (28.4-36.5) -1.024 (-1.175 - -0.873) Both 74948 (65248-87630) 1.8 (1.6-2.2) -0.609 (-0.68 - -0.539) 58825 (51340-68518) 1.4 (1.2-1.7) -0.973 (-1.158 - -0.788) 2889492 (2528098-3356476) 70.5 (60.9-83) -1.008 (-1.192 - -0.825) SDI regions Low SDI Male 4203 (3213-5777) 2 (1.5-2.8) -0.729 (-0.79 - -0.667) 3897 (2972-5383) 1.8 (1.4-2.6) -0.74 (-0.911 - -0.569) 196236 (149930-272152) 90.8 (67.6-128.1) -0.709 (-0.88 - -0.537) Female 2238 (1726-2930) 1 (0.8-1.3) -0.502 (-0.547 - -0.458) 2083 (1598-2736) 0.9 (0.7-1.2) -0.521 (-0.626 - -0.416) 110547 (85051-144711) 47 (35.6-63) -0.5 (-0.602 - -0.397) Both 6441 (4977-8558) 1.5 (1.1-2) -0.67 (-0.724 - -0.616) 5980 (4607-7965) 1.4 (1-1.9) -0.682 (-0.84 - -0.524) 306784 (236783-408649) 68.7 (52.5-93.2) -0.651 (-0.812 - -0.489) Low-middle SDI Male 6715 (5554-8059) 1.4 (1.2-1.8) 0.139 (0.074 - 0.205) 6150 (5079-7367) 1.3 (1.1-1.6) 0.092 (-0.064 - 0.249) 305953 (253343-365501) 64.9 (52.3-81) 0.104 (-0.053 - 0.261) Female 3335 (2937-3749) 0.7 (0.6-0.8) -0.031 (-0.046 - -0.017) 3046 (2676-3433) 0.6 (0.5-0.8) -0.08 (-0.134 - -0.026) 156573 (137464-177440) 32.7 (27.8-38.6) -0.075 (-0.129 - -0.02) Both 10050 (8682-11563) 1.1 (0.9-1.3) 0.063 (-0.006 - 0.132) 9195 (7934-10582) 1 (0.8-1.2) -0.024 (-0.171 - 0.123) 462526 (399447-533079) 48.8 (41.2-57.6) -0.005 (-0.144 - 0.134) Middle SDI Male 27139 (21704-35190) 3.9 (3-5.1) -0.524 (-0.62 - -0.427) 21077 (16965-26899) 3 (2.4-3.9) -1.041 (-1.278 - -0.803) 1026487 (830041-1308962) 149.2 (117.8-192.6) -1.074 (-1.333 - -0.814) Female 5710 (4825-6840) 0.8 (0.7-1) -1.416 (-1.504 - -1.329) 4546 (3864-5392) 0.7 (0.6-0.8) -1.84 (-2.107 - -1.572) 224068 (190890-265331) 33.4 (28.1-39.9) -1.812 (-1.976 - -1.648) Both 32848 (27232-40731) 2.4 (1.9-3) -0.752 (-0.849 - -0.655) 25623 (21354-31427) 1.9 (1.5-2.3) -1.245 (-1.469 - -1.021) 1250555 (1047403-1528716) 91.7 (75.1-113.8) -1.275 (-1.52 - -1.031) High-middle SDI Male 15634 (12142-20283) 4 (3-5.3) -0.496 (-0.635 - -0.357) 11578 (9059-15048) 2.9 (2.2-3.9) -1.104 (-1.446 - -0.762) 558314 (438324-724376) 143 (107.5-189.2) -1.141 (-1.467 - -0.813) Female 2759 (2187-3436) 0.7 (0.6-0.9) -1.165 (-1.37 - -0.96) 2083 (1668-2572) 0.5 (0.4-0.7) -1.669 (-2.133 - -1.202) 100963 (81068-124715) 27.3 (21.5-34.4) -1.715 (-2.175 - -1.254) Both 18393 (14838-23253) 2.4 (1.8-3.1) -0.626 (-0.764 - -0.488) 13661 (11050-17283) 1.8 (1.4-2.3) -1.209 (-1.528 - -0.89) 659278 (532778-833335) 86.1 (67-110.6) -1.249 (-1.562 - -0.934) High SDI Male 5326 (4852-5889) 1.7 (1.5-1.9) -0.996 (-1.096 - -0.895) 3211 (2932-3535) 1 (0.9-1.2) -1.852 (-2.138 - -1.566) 153718 (141204-168465) 49.9 (44.7-56.1) -1.833 (-2.132 - -1.532) Female 1862 (1771-1959) 0.6 (0.6-0.7) 0.423 (0.378 - 0.468) 1130 (1075-1184) 0.4 (0.4-0.4) -0.264 (-0.503 - -0.023) 55449 (52795-57976) 19.6 (18.3-21.1) -0.245 (-0.47 - -0.02) Both 7188 (6677-7806) 1.2 (1.1-1.3) -0.646 (-0.729 - -0.563) 4341 (4041-4694) 0.7 (0.7-0.8) -1.438 (-1.686 - -1.189) 209167 (195748-225096) 35.2 (32.3-38.5) -1.411 (-1.71 - -1.112) WHO regions African Region Male 5813 (4537-7592) 2.7 (2-3.6) -0.725 (-0.791 - -0.659) 5372 (4178-7095) 2.5 (1.9-3.3) -0.755 (-0.861 - -0.649) 272799 (212823-360219) 122.5 (92.5-165.6) -0.716 (-0.819 - -0.614) Female 2831 (2204-3601) 1.2 (0.9-1.6) -0.875 (-0.927 - -0.823) 2620 (2033-3367) 1.1 (0.8-1.4) -0.887 (-1.044 - -0.729) 138131 (106939-177152) 56.3 (43.2-73.7) -0.877 (-1.04 - -0.713) Both 8645 (6793-11096) 1.9 (1.5-2.5) -0.808 (-0.899 - -0.716) 7992 (6248-10352) 1.8 (1.4-2.3) -0.846 (-0.993 - -0.698) 410930 (321576-532186) 88.5 (68.4-116.2) -0.799 (-0.915 - -0.683) Eastern Mediterranean Region Male 2256 (1905-2636) 1.1 (0.9-1.4) 0.059 (-0.02 - 0.137) 2028 (1710-2386) 1 (0.8-1.3) -0.007 (-0.28 - 0.267) 100623 (85311-118076) 50.3 (39.5-63.1) 0.032 (-0.233 - 0.297) Female 1675 (1364-1985) 0.9 (0.7-1.2) -0.377 (-0.427 - -0.327) 1509 (1224-1793) 0.8 (0.6-1.1) -0.505 (-0.685 - -0.325) 77617 (62876-92732) 42.3 (32.9-53.9) -0.44 (-0.709 - -0.169) Both 3931 (3389-4579) 1 (0.9-1.3) -0.126 (-0.168 - -0.085) 3537 (3042-4125) 0.9 (0.8-1.1) -0.197 (-0.425 - 0.031) 178240 (154300-207380) 46.6 (38.2-56.3) -0.143 (-0.362 - 0.076) European Region Male 2570 (2417-2726) 1 (0.9-1.1) 0.56 (0.436 - 0.685) 1863 (1745-1983) 0.7 (0.7-0.8) 0 (-0.462 - 0.465) 89555 (84036-95170) 35.1 (32.5-38.1) -0.019 (-0.488 - 0.452) Female 1139 (1080-1201) 0.4 (0.4-0.5) 0.355 (0.237 - 0.472) 867 (818-922) 0.3 (0.3-0.4) -0.03 (-0.381 - 0.323) 42565 (40142-45204) 17.1 (15.9-18.4) -0.043 (-0.39 - 0.304) Both 3709 (3518-3900) 0.7 (0.7-0.8) 0.504 (0.402 - 0.607) 2730 (2579-2892) 0.5 (0.5-0.6) -0.012 (-0.421 - 0.398) 132120 (125089-139813) 26.1 (24.5-27.9) -0.028 (-0.432 - 0.377) Region of the Americas Male 2052 (1972-2140) 0.8 (0.7-0.8) 0.632 (0.572 - 0.692) 1381 (1319-1444) 0.5 (0.5-0.6) 0.255 (0.05 - 0.46) 68798 (65856-72026) 26.1 (24.5-27.6) 0.3 (0.1 - 0.5) Female 1230 (1167-1302) 0.4 (0.4-0.5) 0.573 (0.529 - 0.617) 910 (858-970) 0.3 (0.3-0.4) 0.348 (0.177 - 0.519) 45306 (42700-48215) 16.5 (15.5-17.7) 0.329 (0.154 - 0.505) Both 3282 (3161-3423) 0.6 (0.6-0.6) 0.625 (0.544 - 0.706) 2291 (2193-2401) 0.4 (0.4-0.4) 0.187 (-0.225 - 0.601) 114105 (109131-119696) 21.2 (20.1-22.4) 0.201 (-0.215 - 0.619) South-East Asia Region Male 7305 (6047-8848) 1.3 (1.1-1.6) 0.103 (0.05 - 0.156) 6572 (5425-7973) 1.2 (0.9-1.5) 0.013 (-0.262 - 0.29) 320582 (264532-389286) 57.6 (46.2-71.9) 0.004 (-0.274 - 0.283) Female 2586 (2087-3074) 0.5 (0.4-0.6) -0.023 (-0.056 - 0.009) 2311 (1877-2758) 0.4 (0.3-0.5) -0.169 (-0.257 - -0.082) 117035 (96571-138727) 21.4 (16.8-26.3) -0.173 (-0.262 - -0.084) Both 9891 (8525-11599) 0.9 (0.8-1.1) 0.038 (-0.004 - 0.08) 8884 (7643-10406) 0.8 (0.7-1) -0.115 (-0.274 - 0.045) 437617 (378152-511082) 39.7 (33.4-47.7) -0.05 (-0.277 - 0.177) Western Pacific Region Male 38646 (30248-49597) 6.8 (5.2-9) -0.468 (-0.541 - -0.395) 28415 (22228-36534) 5 (3.8-6.6) -1.069 (-1.415 - -0.723) 1374927 (1078885-1772272) 246 (187.4-323.7) -1.078 (-1.427 - -0.727) Female 6328 (4986-7926) 1.2 (0.9-1.5) -1.48 (-1.638 - -1.321) 4601 (3608-5736) 0.9 (0.7-1.1) -2.031 (-2.318 - -1.742) 223563 (175730-278263) 42.5 (33.2-54.1) -2.082 (-2.4 - -1.764) Both 44973 (36582-56289) 4.1 (3.2-5.2) -0.64 (-0.709 - -0.571) 33016 (26748-41357) 3 (2.3-3.8) -1.241 (-1.602 - -0.88) 1598491 (1299717-2008652) 146.7 (115.3-186.5) -1.187 (-1.492 - -0.881) DALYs, the disability-adjusted life years; ASR, age-standardizedrate; AAPC, average annual percent change; SDI, socio-demographic index; WHO, world health organization. Additional Declarations No competing interests reported. Supplementary Files FigS1.tif Fig S1 The age-specific number and rates of EOLC by different sexes and SDI regions in 2021. (A) Incidence. (B) Deaths.(C) DALYs. EOLC, early-onset liver cancer; DALYs, the disability-adjusted life years. FigS2.tif Fig S2 The age-specific number and rates of EOLC by different sexes and WHO regions in 2021. (A) Incidence. (B)Deaths. (C) DALYs. EOLC, early-onset liver cancer; SDI, socio-demographic index; DALYs, the disability-adjusted life years. FigS3.tif Fig S3 The age-specific number and rates of EOLC by different sexes and etiologies in 2021. (A) Incidence. (B)Deaths. (C) DALYs. EOLC, early-onset liver cancer; WHO, World Health Organization; DALYs, the disability-adjusted life years. FigS4.tif Fig S4 The percentage of EOLC attributable to different etiologies globally from 1990 to 2021. (A) The percentage change in Males. (B) The percentage change in Females. EOLC, early-onset liver cancer; DALYs, the disability-adjusted life years. TableS1S4.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 09 Feb, 2026 Reviews received at journal 05 Feb, 2026 Reviewers agreed at journal 30 Jan, 2026 Reviews received at journal 26 Jan, 2026 Reviewers agreed at journal 25 Jan, 2026 Reviewers agreed at journal 24 Jan, 2026 Reviewers agreed at journal 21 Jan, 2026 Reviewers invited by journal 26 Dec, 2025 Editor invited by journal 24 Dec, 2025 Editor assigned by journal 16 Dec, 2025 Submission checks completed at journal 16 Dec, 2025 First submitted to journal 16 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8329191","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":565702631,"identity":"fd18a934-b46e-46a6-9fbd-20dd15b3dcfe","order_by":0,"name":"Zhihong Chen","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhihong","middleName":"","lastName":"Chen","suffix":""},{"id":565702635,"identity":"1fad6098-7714-40cd-8465-4ad556b0028b","order_by":1,"name":"Han Zheng","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Han","middleName":"","lastName":"Zheng","suffix":""},{"id":565702636,"identity":"1d04adc9-809b-4b27-81c3-08a3eed95830","order_by":2,"name":"Yunhan Mao","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yunhan","middleName":"","lastName":"Mao","suffix":""},{"id":565702642,"identity":"f67aef46-f3fe-4b90-99ab-83bf1216d32c","order_by":3,"name":"Shunan Zhou","email":"","orcid":"","institution":"Guangdong Provincial People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shunan","middleName":"","lastName":"Zhou","suffix":""},{"id":565702644,"identity":"b2762c8f-a594-4a86-8c77-bd9fd5f8d656","order_by":4,"name":"Shenao Zhang","email":"","orcid":"","institution":"South China University of Technology","correspondingAuthor":false,"prefix":"","firstName":"Shenao","middleName":"","lastName":"Zhang","suffix":""},{"id":565702645,"identity":"4cf42b24-1063-441c-b942-5be731371344","order_by":5,"name":"Yiyao Xu","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yiyao","middleName":"","lastName":"Xu","suffix":""},{"id":565702649,"identity":"310b30fd-bcd4-4892-8e78-4ff0c1243269","order_by":6,"name":"Yaoge Liu","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yaoge","middleName":"","lastName":"Liu","suffix":""},{"id":565702651,"identity":"751a72df-16de-423b-b46b-ea18f7f9156d","order_by":7,"name":"Junwei Zhang","email":"","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Junwei","middleName":"","lastName":"Zhang","suffix":""},{"id":565702658,"identity":"c01130f6-0564-4d0e-a9e1-b92c472b6fa1","order_by":8,"name":"Xin Lu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYBACPiA+AGaxNzY++ECMFja4Fp7DzYYziNUCARLpbdIcRGmRyDE8XLjjcDT/zIcN0gwMdnK6DQS1pCUcnnnmcO6M24kNxgUMycZmBwhqST5wmLftcO4G6cSG5BkMBxK3EdaS2ADRInmw4TAPcVpgtkgwNjYTp4XnWcJh3jPpuTPOJDYzzjAgwi/87DnGn3l3WOf2tx9//uNDhZ0cQS1gwNgAYxkQoxxVyygYBaNgFIwCLAAAOAJEuw3cvIIAAAAASUVORK5CYII=","orcid":"","institution":"Peking Union Medical College Hospital","correspondingAuthor":true,"prefix":"","firstName":"Xin","middleName":"","lastName":"Lu","suffix":""}],"badges":[],"createdAt":"2025-12-10 15:55:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8329191/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8329191/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":99142575,"identity":"889652c4-46a4-430d-a8d9-59ae80a67336","added_by":"auto","created_at":"2025-12-29 08:18:56","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2918271,"visible":true,"origin":"","legend":"\u003cp\u003eDisease burden of EOLC in 204 countries and territories in 1990 and 2021. (\u003cstrong\u003eA-C)\u003c/strong\u003e ASIR,\u003cstrong\u003e \u003c/strong\u003eASMR, and ASDR in 1990. (\u003cstrong\u003eD-F)\u003c/strong\u003e ASIR,\u003cstrong\u003e \u003c/strong\u003eASMR, and ASDR in 2021. \u003cem\u003eEOLC, early-onset liver cancer; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASDR, age-standardized DALYs rate; DALYs, the disability-adjusted life years.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig1.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/9c786d11696384a32a5e6148.jpg"},{"id":99142579,"identity":"23131cd3-c93c-4423-96a0-1304463926c4","added_by":"auto","created_at":"2025-12-29 08:18:56","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":7000921,"visible":true,"origin":"","legend":"\u003cp\u003eTrends of EOLC by different sexes, SDI Regions, and WHO regions from 1990 to 2021.\u003cstrong\u003e (A-C) \u003c/strong\u003eTrends in ASIR.\u003cstrong\u003e (D-F) \u003c/strong\u003eTrends in ASMR. (\u003cstrong\u003eG-I)\u003c/strong\u003eTrends in ASDR.\u003cem\u003e EOLC, early-onset liver cancer; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASDR, age-standardized DALYs rate; DALYs, the disability-adjusted life years. APC, average annual percent change; SDI, socio-demographic index; WHO, World Health Organization.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig2.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/4655f71b195763ab89a68df8.jpg"},{"id":99314905,"identity":"88fe1ffd-4365-4ddd-adae-5f41da9f0c3c","added_by":"auto","created_at":"2025-12-31 16:24:27","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":6458892,"visible":true,"origin":"","legend":"\u003cp\u003eGlobal burden of EOLC. (\u003cstrong\u003eA) \u003c/strong\u003eThe age-specific number and rates of EOLC by different sexes in 2021.\u003cstrong\u003e (B)\u003c/strong\u003eThe percentage of EOLC attributable to different etiologies globally from 1990 to 2021. (\u003cstrong\u003eC) \u003c/strong\u003eThe percentage of EOLC attributable to different etiologies globally in 2021.\u003cem\u003e EOLC, early-onset liver cancer; DALYs, the disability-adjusted life years.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig3.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/2769e71fe07cd9a466bda6eb.jpg"},{"id":99316295,"identity":"afaa6693-0ba9-4b85-acf7-beba7a2f6d79","added_by":"auto","created_at":"2025-12-31 16:28:07","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":3166953,"visible":true,"origin":"","legend":"\u003cp\u003eDecomposition analysis of EOLC from 1990 to 2021 by SDI regions and WHO regions. (\u003cstrong\u003eA)\u003c/strong\u003eDecomposition analysis in incidence.\u003cstrong\u003e (B) \u003c/strong\u003eDecomposition analysis in Deaths. (\u003cstrong\u003eC)\u003c/strong\u003e Decomposition analysis in DALYs. Each bar is composed of three-color blocks: population aging (red), changes in disease trends (blue), and changes in population size (orange). Each black dot represents the net change in ASR of a region between 1990 and 2021, with positive or negative indicating an increase or decrease. \u003cem\u003eEOLC, early-onset liver cancer; DALYs, the disability-adjusted life years; SDI, socio-demographic index; WHO, World Health Organization.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig4.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/d6fe0718fcb122cb5915ded1.jpg"},{"id":99142581,"identity":"f891afef-6a87-44c4-aeed-584f42d4710a","added_by":"auto","created_at":"2025-12-29 08:18:56","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":8463011,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between SDI and burden of EOLC in 204 countries and territories. (\u003cstrong\u003eA) \u003c/strong\u003eAssociation between SDI and ASIR in 2021.\u003cstrong\u003e (B, C) \u003c/strong\u003eFrontier analysis of SDI and ASIR. (\u003cstrong\u003eD)\u003c/strong\u003eAssociation between SDI and ASMR in 2021. (\u003cstrong\u003eE, F) \u003c/strong\u003eFrontier analysis of SDI and ASMR.\u003cstrong\u003e (G) \u003c/strong\u003eAssociation between SDI and ASDR in 2021.\u003cstrong\u003e (H, I) \u003c/strong\u003eFrontier analysis of SDI and ASMR. Orange represents the early period, while dark green represents the recent period. Highlight the 15 countries farthest from the frontier in black, the 5 countries from low SDI regions closest to the border in dark red, and the 5 countries from high SDI regions farthest from the edge in dark blue. The red dots indicate an increase in ASR in 2021 compared to 2019, while the blue dots indicate a decrease. \u003cem\u003eEOLC, early-onset liver cancer; SDI, socio-demographic index; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASDR, age-standardized DALYs rate; DALYs, the disability-adjusted life years.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig5.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/2ad68be63b86b30a3ae06891.jpg"},{"id":99142580,"identity":"61d66689-4998-48e6-bf51-a6e5a73b0bbe","added_by":"auto","created_at":"2025-12-29 08:18:56","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":4858371,"visible":true,"origin":"","legend":"\u003cp\u003eProjected trends in burden of EOLC over the next 29 years using the BAPC model. \u003cstrong\u003e(A) \u003c/strong\u003eASIR in overall, male, and female.\u003cstrong\u003e (B)\u003c/strong\u003e ASMR in overall, male, and female.\u003cstrong\u003e (C) \u003c/strong\u003eASDR in overall, male, and female. \u003cem\u003eEOLC, early-onset liver cancer; BAPC, Bayesian Age-Period-Cohort; ASIR, age-standardized incidence rate; ASMR, age-standardized mortality rate; ASDR, age-standardized DALYs rate; DALYs, the disability-adjusted life years.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig6.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/4b4d9e8c84202391cea38e26.jpg"},{"id":99323534,"identity":"82251f3a-9c9d-48cb-b969-39ffc2da6c9a","added_by":"auto","created_at":"2025-12-31 16:45:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":33814905,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/dbb03eeb-674b-46c7-9b9d-bd4342ebfb1e.pdf"},{"id":99142583,"identity":"c1517457-651f-47e2-bb9b-066b3c0a144f","added_by":"auto","created_at":"2025-12-29 08:18:59","extension":"tif","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":128908752,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig S1 \u003c/strong\u003eThe age-specific number and rates of EOLC by different sexes and SDI regions in 2021.\u003cstrong\u003e (A)\u003c/strong\u003e Incidence. \u003cstrong\u003e(B) \u003c/strong\u003eDeaths.\u003cstrong\u003e(C)\u003c/strong\u003e DALYs.\u003cem\u003e EOLC, early-onset liver cancer; DALYs, the disability-adjusted life years.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"FigS1.tif","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/2d4bed205f9913893b8a2939.tif"},{"id":99142584,"identity":"a50deef8-e941-480d-9f6a-593ac782aa39","added_by":"auto","created_at":"2025-12-29 08:19:00","extension":"tif","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":132238068,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig S2 \u003c/strong\u003eThe age-specific number and rates of EOLC by different sexes and WHO regions in 2021. \u003cstrong\u003e(A) \u003c/strong\u003eIncidence.\u003cstrong\u003e (B)\u003c/strong\u003eDeaths. \u003cstrong\u003e(C)\u003c/strong\u003e DALYs. \u003cem\u003eEOLC, early-onset liver cancer; SDI, socio-demographic index; DALYs, the disability-adjusted life years.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"FigS2.tif","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/1096634bf776d790fcdd6ad7.tif"},{"id":99142585,"identity":"9fb98086-73ca-4db8-bd25-65074a3ce4c7","added_by":"auto","created_at":"2025-12-29 08:19:00","extension":"tif","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":129378592,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig S3 \u003c/strong\u003eThe age-specific number and rates of EOLC by different sexes and etiologies in 2021. \u003cstrong\u003e(A) \u003c/strong\u003eIncidence. \u003cstrong\u003e(B)\u003c/strong\u003eDeaths. \u003cstrong\u003e(C)\u003c/strong\u003e DALYs. \u003cem\u003eEOLC, early-onset liver cancer; WHO, World Health Organization; DALYs, the disability-adjusted life years.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"FigS3.tif","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/cdeeea23ca76cc1aabba7734.tif"},{"id":99142582,"identity":"7745e047-2721-4e26-aebf-df7739244d5f","added_by":"auto","created_at":"2025-12-29 08:18:59","extension":"tif","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":110305780,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig S4 \u003c/strong\u003eThe percentage of EOLC attributable to different etiologies globally from 1990 to 2021. \u003cstrong\u003e(A) \u003c/strong\u003eThe percentage change in Males. \u003cstrong\u003e(B)\u003c/strong\u003e The percentage change in Females. \u003cem\u003eEOLC, early-onset liver cancer; DALYs, the disability-adjusted life years.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"FigS4.tif","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/30c276e1d1bb65b83250a9e9.tif"},{"id":99315718,"identity":"fdd129c5-4e01-4620-ad83-c93fc44a80b6","added_by":"auto","created_at":"2025-12-31 16:27:17","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":44059,"visible":true,"origin":"","legend":"","description":"","filename":"TableS1S4.docx","url":"https://assets-eu.researchsquare.com/files/rs-8329191/v1/a23be3af1caaa58ef50cde18.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Trends in global early-onset liver cancer from 1990 to 2050: an analysis of the Global Burden of Disease Study 2021","fulltext":[{"header":"1\tIntroduction","content":"\u003cp\u003eAccording to GLOBOCAN 2022, liver cancer (LC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide [1]. Hepatocellular carcinoma (HCC), which accounts for 75-85% of primary LC cases, followed by intrahepatic cholangiocarcinoma (ICC, 10-15%) and other rare types. Major risk factors include chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, exposure to carcinogens, metabolic dysfunction, and genetic predisposition [2]. Although HBV vaccination and antiviral therapy have reduced the incidence of virus-associated LC, the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcoholic liver disease (ALD) is driving an increasing global burden of LC [3].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWith advances in cancer screening, the proportion of early-onset cancers, diagnosed before age 50, has increased in many countries, possibly reflecting cumulative early life exposure to adverse environments or lifestyles [4]. Emerging evidence has compared early-onset cancer (EOLC) and late-onset cancer (LOLC) in terms of etiology, clinical manifestations, tumor biology, and outcomes. Beyond viral hepatitis, metabolic disorders and alcohol abuse are key contributors to EOLC [5]. EOLC often presents with less cirrhosis, leading to delayed or missed diagnosis. In addition, EOLC usually exhibits more aggressive biological features, including high-grade histology, metastasis, or lymph node involvement, which may lead to a worse prognosis. However, early detection and timely intervention can significantly improve outcomes for EOLC patients compared to LOLC patients, underscoring the need to extend screening to younger, high-risk populations [6\u0026ndash;8].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResearch shows that while the absolute burden of EOLC increased from 1990 to 2021 globally, the age-standardized rates (ASRs) of incidence, mortality, and disability adjusted life year (DALY) have decreased slightly [9]. Besides, Significant geographic heterogeneity persists, with DALYs attributable to metabolic risks rising markedly, especially among young adults with both HBV and obesity [10]. Furthermore, GLOBOCAN 2022 reports a notable increase in EOLC incidence in Northern Europe, driven largely by rising ICC rates, particularly among women in North America, Western Europe, Australia, and New Zealand [11].\u003c/p\u003e\n\u003cp\u003eThis study leverages the Global Burden of Disease (GBD) 2021 data to comprehensively assess the EOLC burden from 1990 to 2021, characterize its spatiotemporal patterns, and project trends through 2050. Building on prior work, our analysis incorporates stratification, decomposition, and efficiency frontier methods to identify key drivers and dynamic shifts in disease burden, providing robust evidence to inform targeted prevention and control strategies for at-risk populations.\u003c/p\u003e"},{"header":"2\tMaterials and Methods","content":"\u003cp\u003e\u003cstrong\u003e2.1\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Data source\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGBD 2021 provides comprehensive estimates of the epidemiological burden for 371 diseases and injuries, along with 88 key risk factors, across 204 countries and territories. It employs an integrated modeling framework that synthesizes data from national health systems, disease surveillance, cancer registries, population-based surveys, and peer-reviewed literature [12]. Using the Global Health Data Exchange (GHDx) query tool (https://ghdx.healthdata.org/gbd-2021), we extracted age-specific burden estimates for early-onset liver cancer (EOLC) among individuals aged 15–49 years from 1990 to 2021, focusing on incidence, mortality, and DALYs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Data Processing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAge-standardized rates and their 95% uncertainty intervals (UIs) for individuals aged 15–49 years were calculated using the GBD world population age-standard weights and age-specific rates across seven 5-year age groups (15–19 to 45–49 years).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Data Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe compared the global burden of EOLC between 1990 and 2021, stratifying by sex, age, etiology, and region. Joinpoint regression was used to estimate the annual percent change (APC), average annual percent change (AAPC), and 95% confidence intervals (CIs), capturing both short-term fluctuations and long-term trends. Decomposition analysis attributed changes in disease burden to population growth, aging, and epidemiological shifts. To assess the relationship between EOLC burden and socioeconomic development, we plotted ASRs against the Socio-demographic Index (SDI) for 204 countries in 2021, fitting a LOESS curve. An SDI-efficiency frontier, constructed via bootstrap resampling and cumulative minimum methods, identified countries with high or low performance in burden control relative to their SDI. Finally, using GBD data, we applied a Bayesian age-period-cohort (BAPC) model to project global age-standardized incidence, mortality, and DALY rates for individuals aged 15–49 years from 2022 to 2050, with separate models by sex.\u003c/p\u003e\n\u003cp\u003eAs this study used anonymized data from publicly available sources, institutional ethical approval and informed consent were not required.\u003c/p\u003e"},{"header":"3\tResults","content":"\u003cp\u003e\u003cstrong\u003e3.1\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Global burden of EOLC from 1990 to 2021\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 1 and Table S1 summarize the global burden of EOLC in 1990 and 2021, and detail absolute numbers, ASRs, and AAPCs of incidence, deaths, DALYs by region and sex. Fig 1 visually illustrates the spatial distribution of EOLC across 204 countries and territories in 1990 and 2021.\u003c/p\u003e\n\u003cp\u003eIn 2021, EOLC accounted for approximately 74,948 new cases (95% UI: 65,248–87,630), 58,825 deaths (95% UI: 51,340–68,518), and 2,889,492 DALYs (95% UI: 2,528,098–3,356,476) globally, marking a substantial increase in absolute burden since 1990. However, ASRs declined over the same period, indicating reduced risk after adjusting for population structure. The age-standardized incidence rate (ASIR) decreased from 2.2 to 1.8 per 100,000, the mortality rate (ASMR) from 2.0 to 1.4 per 100,000, and the DALY rate (ASDR) from 97.3 to 70.5 per 100,000. Corresponding average annual percent changes (AAPCs) were −0.609 for ASIR, −0.973 for ASMR, and −1.008 for ASDR (all \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), reflecting consistent long-term declines.\u003c/p\u003e\n\u003cp\u003eIn 2021, the burden of EOLC was markedly higher in males than in females, with 59,037 cases (ASIR: 2.8 per 100,000), 45,930 deaths (ASMR: 2.2 per 100,000), and 2,241,536 DALYs (ASDR: 108.4 per 100,000). Despite this disparity, ASRs declined more rapidly in females than in males. Female AAPCs were −0.712 for ASIR, −1.009 for ASMR, and −1.024 for ASDR, compared to −0.565, −0.928, and −0.971 in males, respectively (all 95% CIs excluding zero).\u003c/p\u003e\n\u003cp\u003eIn 2021, the highest age-standardized rates (ASRs) were observed in the middle SDI region (ASIR: 2.4, ASMR: 1.9, ASDR: 91.7 per 100,000), while the high SDI region had the lowest ASMR (0.7) and ASDR (35.2). From 1990 to 2021, ASRs generally declined across most SDI groups, with the steepest reductions in the middle SDI region. Notable exceptions were rising ASIRs among women in high SDI countries (AAPC = 0.423) and men in low-middle SDI countries (AAPC = 0.139).\u003c/p\u003e\n\u003cp\u003eAmong WHO regions, the Western Pacific bore the highest EOLC burden in 2021, with an ASIR of 4.1, ASMR of 3.0, and ASDR of 146.7 per 100,000. From 1990 to 2021, ASIR significantly declined in the African, Eastern Mediterranean, and Western Pacific regions (AAPC \u0026lt; 0, P \u0026lt; 0.05), with the steepest drop in the Western Pacific. In contrast, ASIR increased in the European and American regions (AAPC \u0026gt; 0, P \u0026lt; 0.05), while no significant trend was observed in South-East Asia. Notably, both males and females in the Americas showed rising ASMR and ASDR (AAPC \u0026gt; 0).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn terms of the number of incidences, deaths, and DALYs, China, India, and Vietnam were the top three countries with the highest absolute burden in the world. In terms of incidence, China (50232; 95% UI: 38509-61051) was far higher than India (6105, 95% UI: 5134-7373) and Vietnam (3200, 95% UI: 2038-4373), making it the country with the heaviest absolute burden. In terms of deaths, China was also significantly higher than the other two countries, ranking first (36519, 95% UI: 28127-44788). China had the heaviest burden of DALYs (1769074, 95% UI: 1363072-2175076), followed by India (277039, 95% UI: 232488-321590), and Vietnam (131652, 95% UI: 85041-178263).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn 2021, Mongolia, Gambia, and Eswatini had the highest ASIR (12.9, 95% UI: 8.4-19.2; 12.3, 95% UI: 6-22.9; 8.6, 95% UI: 2.3-23.1, respectively). Their ASMR was also the highest (12.0, 95% UI: 7.9-17.8; 11.4, 95%UI：5.6-21.1; 8.0, 95% UI: 2.1-21.3, respectively). Similarly, the top three countries in ASDR were Mongolia (569.5, 95% UI: 372.2-841.8), Gambia (546.2, 95% UI: 269.2-1016.5), and Eswatini (389.6, 95% UI: 103.7-1047.3). Between 1990 and 2021, the ASIR of EOLC in Mongolia slightly decreased, but it was statistically significant (AAPC=-0.168, 95% CI: -0.272 to -0.065). In contrast, the decline trends of ASMR and ASDR were not statistically significant. On the contrary, the incidence rate of Gambia and Eswatini shows an upward trend: the APCC of ASIR for Gambia ASIR was 0.345 (95% CI: 0.148-0.543), while that of ASIR for Eswatini rises sharply to 3.593 (95% CI: 3.300-3.886). In addition, Eswatini also increased significantly in ASMR (AAPC=3.618, 95% CI: 3.332-3.905) and ASDR (AAPC=3.627, 95% CI: 3.323-3.931).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFig 2A, 2D, and 2E show gender-specific temporal trends of ASRs in EOLC. Among men, ASIR increased from 1990 to 2000, decreased from 2001 to 2005, slightly increased from 2006 to 2013, and gradually decreased after 2014. Among women, ASIR slowly increased from 1990 to 2000, then steadily decreased until there was less fluctuation after 2006. Similar patterns were observed in ASMR and ASDR. Fig 2B, 2E, and 2H present the ASR trends of EOLC across different SDI levels. In low SDI regions, ASRs began to decline after 1996. High SDI regions initially increased, but then continued to decline from around 2000. Middle SDI regions experienced a sharp decline after 2000, rebounded slightly after 2006, and gradually declined from 2016 onwards. Fig 2C, 2F, and 2I show Joinpoint regression results of ASRs in WHO regions. In the Western Pacific and African regions, ASRs have shifted from an upward trend to a downward trend since 2001, and have further declined since 2006. They have been on a downward trend since 2010. In contrast, ASRs in the Eastern Mediterranean, European, American, and Southeast Asian regions only showed slight fluctuations over time.\u003c/p\u003e\n\u003cp\u003eAs shown in Fig 3A, the incidence rate, mortality, and DALYs related to EOLC gradually increase with age, and men always bear a higher burden than women. Fig S1-S3 further illustrate that the burden of EOLC varies by gender, region, and underlying etiology in different age groups, but typically shows an upward trend, especially in men, the growth of the elderly is more rapid. The absolute burden of cancer caused by NASH and others is higher in females aged 15-29 than in males of the same age group (Fig S3).\u003c/p\u003e\n\u003cp\u003eFig 3B shows the changes in the etiological composition of the total burden between 1990 and 2021. In 1990, HBV accounted for the majority of cases (71.8%), followed by HCV (8.9%), alcohol consumption (8.8%), and non-alcoholic steatohepatitis (NASH) (4.3%). By 2021, HBV remained the main cause (67.9%), although its relative contribution has slightly decreased. During the same period, the proportion of cases caused by HCV increased to 9.5%, the proportion of cases related to alcohol slightly increased to 11.1%, and the proportion of cases related to NASH increased to 5.7%. The mortality rate also showed a similar pattern: the proportion of deaths caused by HBV decreased from 72.3% to 67.4%, while alcohol-related deaths increased from 8.6% to 11.2%, HCV-related deaths increased from 8.6% to 9.6%, and NASH-related deaths increased from 4.3% to 6%. DALYs also showed a similar trend, with HBV still dominating (72.8% in 1990 and 67.7% in 2021), and alcohol, HCV, and NASH contributing increasingly. Fig S4 shows that alcohol, HCV, and NASH are increasingly contributing to carcinogenesis in both males and females, in addition to HBV. However, from 1990 to 2021, the proportion of LC caused by alcohol increased significantly in males, while the proportion of LC caused by HCV and NASH increased significantly in females.\u003c/p\u003e\n\u003cp\u003eFig 3C illustrates the distribution of the etiologies of EOLC in different age groups. Overall, HBV remained the main cause. It was worth noting that as age increased, the relative contribution rate of NASH decreased, while the proportion of HCV and alcohol consumption increased accordingly.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDecomposition analysis of burden of EOLC in different regions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDecomposition analysis revealed that the increase in the incidence rate of EOLC was mainly driven by population growth and aging. Although the epidemiological component was negative, indicating that ASIR actually declined. The population pressure exceeded this positive trend. The changes in mortality were similar. Although epidemiological factors suggest that the risk of death may decrease (negative ASMR), the total number of deaths has increased, mainly due to population growth and aging. Likewise, DALYs have also increased. Although epidemiological factors remained negative (negative ASDR), they were still insufficient to offset the significant impact of population growth and aging (Fig 4A).\u003c/p\u003e\n\u003cp\u003eAcross WHO regions, the incidence rate of early-onset cancer in the Western Pacific region has increased the most, mainly due to the aging of the population. Although the epidemiological factors were negative, reflecting the decline in incidence, this favorable trend was offset by population pressures. The South-East Asia region has the highest absolute numbers of deaths and DALYs, followed by the African region. The rapid population growth was the dominant driver of the rising burden. In contrast, the net changes in the Americas, Europe, and the Eastern Mediterranean regions are relatively small, showing a slight overall increase. It is worth noting that the epidemiological factors in Americas and Europe are slightly positive (Fig 4B).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe increase in EOLC cases and deaths in low SDI and low-middle SDI regions was mainly attributed to population growth, resulting in a continued increase in the overall burden. On the contrary, in high SDI and middle-high SDI regions, epidemiological factors remained negative, indicating a decrease in DALYs and a relatively low overall burden (Fig 4C).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.2\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;The relationship between the burden of EOLC and SDI\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFig 5A, 5D, and 5E show that in 204 countries and territories. The ASIR, ASMR, and ASDR of EOLC generally decrease with the increase of SDI, and the trend tends to be flat and slightly increased. Overall, countries and territories with higher SDI categories had maintained relatively low tumor burden. It was worth noting that Mongolia, Gambia, and Eswatini significantly deviated from the LOESS curve, reflecting a significant increase in the burden that cannot be explained by SDI alone.\u003c/p\u003e\n\u003cp\u003eThe frontier analysis of the relationship between the SDI and ASRs of ELOC in 204 countries and territories from 1990 to 2021 revealed a general reverse association. ASIR, ASMR, and ASDR tended to decrease and concentrate with the increasing SDI (Fig 5B, 5E, and 5H). Besides, the frontier analysis evaluated national performance in 2021 by comparing the observed tumor burden with the optimal level achievable by SDI of each country.\u003c/p\u003e\n\u003cp\u003eFor ASIR, the ASIR of 15 countries, including Mongolia, Gambia, and Eswatini, increased significantly, far below the frontier, indicating their serious disease burden. In contrast, Somalia, Burundi, Ethiopia, Yemen, Haiti, and other low SDI countries were closer to the frontier, which showed that their limited socio-economic resources were relatively effective in preventing and controlling EOLC. Compared to their level of development, this poor performance highlighted the need for increased attention to the emerging or persistent burden of EOLC in other high-resource environments (Fig 5C, 5F, and 5I).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.3\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Global burden of EOLC from 2021 to 2050 predicted by the BAPC model\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFrom 1990 to 2020, ASRs of EOLC, including ASIR, ASMR, and ASDR, followed a consistent time pattern in the overall, male, and female population: initially increasing, then decreasing, and finally stabilizing at a relatively stable or slightly lower stable period around 2020. Since 2020, the overall ASIR has been declining year by year, with men experiencing a greater decline, while women have experienced moderate but stable annual growth (Fig 6A-6C).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe forecast by 2050 indicates that the overall ASIR will decrease to 1.577 new cases per 100,000 population (95% UI: 1.57677-1.57684). It is expected that the ASIR of males will significantly decrease to 2.063 (95% UI: 2.06287-2.06296), while the ASIR of females will slightly increase to 0.880 (95% UI: 0.87990-0.87993), consistently lower than males and only showing a mild upward trend. The specific values of ASRs are shown in Tables S2-S4. Similarly, the overall ASMR is expected to decrease to 1.206 deaths per 100,000 population (95% UI: 1.20599-1.20605), mainly due to a larger decline in male ASMR (1.533; 95% UI: 1.53338-1.53347), while female ASMR will slightly increase to 0.696 (95% UI: 0.69590-0.69592). For ASDR, the overall incidence rate is expected to decline to 61.89 cases per 100,000 population (95% UI: 61.8860-61.88904), male ASDR will decline significantly to 79.87 (95% UI: 79.86857-79.87270), and female ASDR will rise slightly to 36.56 (95% II: 36.55914-36.56051). Although ASMR and ASDR in women are expected to increase moderately, their absolute burden is still relatively low, and the magnitude of the increase is limited.\u003c/p\u003e"},{"header":"4\tDiscussions","content":"\u003cp\u003eUnlike previous studies [10,13], this study used the BAPC model to project EOLC trends to 2050 based on the GBD 2021 dataset, integrating various methods such as joint point regression, decomposition analysis, LOESS, and frontier analysis.\u003c/p\u003e\n\u003cp\u003eE EOLC primarily affects middle-aged individuals, with risk rising with age and peaking at 45\u0026ndash;59 years, underscoring its strong link to aging [14]. In 2021, the global absolute burden of EOLC increased, with men bearing a significantly higher burden than women. Although women had a slightly higher AAPC, men exhibited a substantially greater APC, a disparity likely attributable not only to biological factors (e.g., sex hormones) but also to gender differences in exposure to modifiable environmental and behavioral risk factors \u0026nbsp;[15,16].\u003c/p\u003e\n\u003cp\u003eGlobally, ASRs, particularly ASMR and ASDR, rose until around 2000 before declining significantly, likely due to widespread hepatitis B vaccination and antiviral therapy introduced in the 1990s [17,18]. This trend is similar to the global epidemiological changes in overall LC [19]. Due to data limitations, this study was unable to assess epidemiological trends by liver cancer subtype. SEER data indicated that from 2010 to 2019, the incidence rate of early-onset HCC declined (APC was \u0026minus; 4.67%), while the incidence rate of early-onset ICC increased (APC was+8.12%)[20].\u003c/p\u003e\n\u003cp\u003eGeographically, the highest EOLC burden remains in middle, high-middle SDI, and Western Pacific regions, although their ASRs have gradually declined, reflecting progress toward the WHO\u0026rsquo;s goal to eliminate hepatitis B by 2030 [18]. In contrast, rising ASIRs have been observed among males in low-middle SDI regions, females in high SDI regions, and populations in Europe and the Americas, primarily driven by increasing NASH [21,22]. In high SDI regions, the rise in female incidence may stem not only from improved screening and HBV control but also from growing contributions of HCV, NASH, and alcohol use [3]. These changes highlight the urgent need for targeted early detection strategies for emerging high-risk groups. In addition, for different races/ethnicities in different regions, it is also necessary to pay attention to the influence of other factors, such as comorbidities [23].\u003c/p\u003e\n\u003cp\u003eEtiological analysis reveals a shifting global etiology profile of EOLC. Although the relative contribution of HBV has slightly decreased, HBV-related LC remains dominant, accounting for over 60% of cases, predominantly in males. Despite widespread vaccination, the large reservoir of chronic HBV infections and long-term latency of disease ensure its continued substantial contribution to the cancer burden in the coming years. Sustained efforts to vaccinate newborns and expand access to antiviral treatment for adults remain critical, requiring at least a 2% annual decrease in ASIR to effectively curb burden growth [24]. In addition, Viral hepatitis is more prevalent in low- and middle-income countries, while alcohol use and obesity are more common in high-income countries [25].\u003c/p\u003e\n\u003cp\u003eALD has become the second leading cause of EOLC, with its attributable fraction steadily rising, especially among males, underscoring the urgent need for stricter alcohol control policies and targeted public health interventions [26]. HCV ranks third. Its contribution among women has significantly increased in recent years. Given the availability of highly effective antiviral therapies, HCV-related LC is now largely preventable and curable, and further expanding screening and treatment coverage could substantially reduce this burden [27,28]. NASH is the fourth leading cause, showing a moderate but sustained increase, especially in populations with high body mass index and fasting blood glucose, likely driven by the global rise in obesity and metabolic syndrome [29,30]. As risk factors prevalent among young people, NASH and alcohol will become the main non-communicable drivers of cancer burden in the coming decades [29,31]. This study did not include data on EOLC burden in children and therefore did not assess hepatoblastoma. A study has reported declining overall incidence and mortality of hepatoblastoma, alongside a rising proportion of liver cancer cases attributable to NASH and alcohol [32].\u003c/p\u003e\n\u003cp\u003eAlthough traditional infectious causes of EOLC have been effectively controlled, emerging metabolic and behavioral risk factors are rapidly filling the epidemiological gap [12]. Curbing the rising burden of EOLC requires shifting from single-target antiviral strategies to a comprehensive, multifactorial approach through enhanced early detection, risk-stratified interventions, and cross-sectoral public health collaboration.\u003c/p\u003e\n\u003cp\u003eDecomposition analysis shows that, despite a rising absolute burden, the ASR of EOLC has declined, indicating reduced underlying epidemiological severity after adjusting for population growth and aging, and reflecting the success of current prevention efforts. China and India have a relatively high absolute disease burden due to their population base. Moreover, data from GLOBOCAN 2020 and GBD 2019 indicated that the burden is increasing with global population aging and ranked as the fifth leading cause of cancer-related death worldwide (ASMR = 47.7%)\u0026nbsp;[33]. The high prevalence of comorbidities in older adults, particularly cardiovascular disease, diabetes, and chronic respiratory diseases, complicates clinical management, heightens care demands, and imposes substantial socioeconomic strain [34,35]. Strengthening comprehensive prevention and control strategies is therefore essential to further reduce the LOLC burden and address the complex health needs of aging populations.\u003c/p\u003e\n\u003cp\u003eEfficiency frontier analysis identifies five low-SDI countries, Somalia, Burundi, Ethiopia, Haiti, and Yemen, as closest to the optimal EOLC prevention and control frontier. Despite limited resources, their relatively strong performance warrants an in-depth study of context-specific strategies that may offer scalable lessons. In contrast, Mongolia, The Gambia, and Eswatini lie furthest from the frontier, reflecting both a high EOLC burden and suboptimal control outcomes. These countries urgently require tailored public health responses aligned with local epidemiology, including enhanced early screening, targeted etiological interventions (e.g., antiviral therapy, alcohol and metabolic risk management), and strengthened healthcare infrastructure to improve overall cancer prevention and control capacity [36,37].\u003c/p\u003e\n\u003cp\u003eThe BAPC model predicts a continued decline in the overall ASR of EOLC over the next 29 years, with the notable exception of women, whose burden may rise. Our findings indicate that NASH is becoming increasingly common among young women, with a relatively high proportion among adolescents aged 15-29, which may be a key factor in this trend, especially among women. An analysis of GBD 2021 indicated that the global burden of NAFLD continues to rise, with high-risk populations mainly consisting of youth, middle-aged men, and older women [38]. Future EOLC prevention strategies must address gender and regional health inequities through targeted interventions to mitigate emerging risk factors like NASH and ensure equitable progress in global cancer control.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThis study has several limitations. Firstly, due to differences in disease surveillance systems, diagnostic capabilities, and reporting standards across regions, EOLC data exhibits heterogeneity in source and quality, which may lead to incomplete or inaccurate data, thereby introducing reporting bias and affecting the estimation of true disease burden. Secondly, this study did not include pathological subtyping information of liver cancer, making it impossible to further evaluate the burden of different subtypes. Finally, although future trend predictions are based on strict BAPC models, they may still be affected by unforeseeable factors in the future, such as adjustments in public health policies, the emergence of new risk factors, socio-economic changes, or advances in medical technology, which can deviate from the predicted trajectory. Therefore, although this study provides valuable evidence for the spatiotemporal heterogeneity of global EOLC, the interpretation of the results still needs to be cautious, and localized analysis and application should be combined with specific social, economic, and health backgrounds in each region.\u003c/p\u003e"},{"header":"5\tConclusion","content":"\u003cp\u003eOur study elucidates the epidemiology and future trends of EOLC, revealing an overall declining disease burden but persistent disparities by gender and region. These findings underscore the need to shift from broad prevention toward equitable, precision-focused strategies, particularly through enhanced etiological research, early screening in high-risk women, and targeted interventions against emerging risk factors. Prioritizing high-burden and underperforming regions is essential to achieving fair and sustainable global EOLC control.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eLC Liver cancer\u003c/p\u003e\n\u003cp\u003eHCC Hepatocellular carcinoma\u003c/p\u003e\n\u003cp\u003eICC Intrahepatic cholangiocarcinoma\u003c/p\u003e\n\u003cp\u003eHBV Hepatitis B virus\u003c/p\u003e\n\u003cp\u003eHCV Hepatitis C virus\u003c/p\u003e\n\u003cp\u003eMASLD Metabolic dysfunction-associated steatotic liver disease\u003c/p\u003e\n\u003cp\u003eALD Alcoholic liver disease\u003c/p\u003e\n\u003cp\u003eEOLC Early-onset liver cancer\u003c/p\u003e\n\u003cp\u003eLOLC Late-onset liver cancer\u003c/p\u003e\n\u003cp\u003eASR Age-standardized rate\u003c/p\u003e\n\u003cp\u003eASIR Age-standardized incidence rate\u003c/p\u003e\n\u003cp\u003eASMR Age-standardized mortality rate\u003c/p\u003e\n\u003cp\u003eASDR Age-standardized disability-adjusted life year rate\u003c/p\u003e\n\u003cp\u003eDALY Disability-adjusted life year\u003c/p\u003e\n\u003cp\u003eUI Uncertainty interval\u003c/p\u003e\n\u003cp\u003eCI Confidence interval\u003c/p\u003e\n\u003cp\u003eAPC Annual percent change\u003c/p\u003e\n\u003cp\u003eAAPC Average annual percent change\u003c/p\u003e\n\u003cp\u003eSDI Socio-demographic Index\u003c/p\u003e\n\u003cp\u003eLOESS Locally estimated scatterplot smoothing\u003c/p\u003e\n\u003cp\u003eGHDx Global Health Data Exchange\u003c/p\u003e\n\u003cp\u003eGBD Global Burden of Disease\u003c/p\u003e\n\u003cp\u003eBAPC Bayesian age-period-cohort\u003c/p\u003e\n\u003cp\u003eWHO World Health Organization\u003c/p\u003e\n\u003cp\u003eNAFLD Nonalcoholic fatty liver disease\u003c/p\u003e\n\u003cp\u003eNASH Nonalcoholic steatohepatitis\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the GBD Study collaborators for their work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYaoge Liu, Junwei Zhang, and Xin Lu contributed to the study conception and design. Material preparation, data collection and analysis were performed by Zhihong Chen and Han Zheng, Shunan Zhou, Shenao Zhang, Yunhan Mao, and Yiyao Xu. The first draft of the manuscript was written by Zhihong Chen and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval and accordance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during the current study are available in the GBD database (https://gbd2021.healthdata.org/gbd-results/).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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Nowcasting and forecasting global aging and cancer burden: analysis of data from the GLOBOCAN and Global Burden of Disease Study. Journal of the National Cancer Center. 2024;4:223\u0026ndash;32. https://doi.org/10.1016/j.jncc.2024.05.002\u003c/li\u003e\n\u003cli\u003eChen W, Altshuler RD, Daschner P, Salvador Morales C, St. Germain DC, Guida J, et al. Older adults with cancer and common comorbidities\u0026mdash;challenges and opportunities in improving their cancer treatment outcomes. JNCI: Journal of the National Cancer Institute. 2024;116:1730\u0026ndash;8. https://doi.org/10.1093/jnci/djae163\u003c/li\u003e\n\u003cli\u003eIslam MT, Saif MSI, Alam N, Pepper S, Ratnayake I, Mudaranthakam DP. Evaluating the risk of comorbidity onset in elderly patients after a cancer diagnosis. BMC Public Health. 2025;25:640. https://doi.org/10.1186/s12889-025-21784-7\u003c/li\u003e\n\u003cli\u003eLi Q, Ding C, Cao M, Yang F, Yan X, He S, et al. Global epidemiology of liver cancer 2022: An emphasis on geographic disparities. Chinese Medical Journal. 2024;137:2334\u0026ndash;42. https://doi.org/10.1097/CM9.0000000000003264\u003c/li\u003e\n\u003cli\u003eJiang Z, Zeng G, Dai H, Bian Y, Wang L, Cao W, et al. Global, regional and national burden of liver cancer 1990\u0026ndash;2021: a systematic analysis of the global burden of disease study 2021. BMC Public Health. 2025;25:931. https://doi.org/10.1186/s12889-025-22026-6\u003c/li\u003e\n\u003cli\u003eTang J, Zheng N, Yan Y-X, Zhang N, Ren X-M. 1990\u0026ndash;2021 global, regional, and national analysis of the burden and trends of non-alcoholic fatty liver disease. Front Med. 2025;12:1609816. https://doi.org/10.3389/fmed.2025.1609816\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp style=\"margin:0cm;text-align:justify;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eTable 1. \u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eThe number, ASR and AAPC of early-onset liver cancer by global, SDI regions, WHO regions in 2021\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border: none;width:1115.0pt;border-collapse:collapse;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width:150.0pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eLocation\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width:40.0pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid black 1.0pt;border-right:none;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eSex\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:284.0pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eIncidence\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:285.0pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eDeaths\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width:356.0pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eDALYs\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:104.8pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eNumber (95%UI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eASR (95%UI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eAAPC (95%CI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eNumber (95%UI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eASR (95%UI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eAAPC (95%CI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eNumber (95%UI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eASR (95%UI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eAAPC (95%CI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:150.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eGlobal\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e59037 (49998-72069)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2.8 (2.4-3.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.565 (-0.64 - -0.49)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e45930 (38909-55822)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2.2 (1.8-2.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.928 (-1.132 - -0.722)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2241536 (1901989-2722915)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n 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style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.024 (-1.175 - -0.873)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eBoth\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e74948 (65248-87630)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n 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5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e70.5 (60.9-83)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.008 (-1.192 - -0.825)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:150.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eSDI regions\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n 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style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e4203 (3213-5777)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2 (1.5-2.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.729 (-0.79 - -0.667)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp 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5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.502 (-0.547 - -0.458)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2083 (1598-2736)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.9 (0.7-1.2)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.521 (-0.626 - -0.416)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e110547 (85051-144711)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e47 (35.6-63)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.5 (-0.602 - -0.397)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eBoth\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e6441 (4977-8558)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.5 (1.1-2)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.67 (-0.724 - -0.616)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e5980 (4607-7965)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 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5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e68.7 (52.5-93.2)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.651 (-0.812 - -0.489)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:150.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eLow-middle SDI\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n 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style=\"width:112.55pt;background:#F4B084;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.139 (0.074 - 0.205)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e6150 (5079-7367)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.3 (1.1-1.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.092 (-0.064 - 0.249)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e305953 (253343-365501)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e64.9 (52.3-81)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n 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style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eBoth\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e10050 (8682-11563)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.1 (0.9-1.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.063 (-0.006 - 0.132)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e9195 (7934-10582)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1 (0.8-1.2)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.024 (-0.171 - 0.123)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e462526 (399447-533079)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e48.8 (41.2-57.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.005 (-0.144 - 0.134)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:150.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eMiddle SDI\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e27139 (21704-35190)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e3.9 (3-5.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.524 (-0.62 - -0.427)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e21077 (16965-26899)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e3 (2.4-3.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.041 (-1.278 - -0.803)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1026487 (830041-1308962)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e149.2 (117.8-192.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.074 (-1.333 - -0.814)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e5710 (4825-6840)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.8 (0.7-1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.416 (-1.504 - -1.329)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e4546 (3864-5392)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.7 (0.6-0.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.84 (-2.107 - -1.572)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e224068 (190890-265331)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e33.4 (28.1-39.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n 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style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1250555 (1047403-1528716)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e91.7 (75.1-113.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.275 (-1.52 - -1.031)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:150.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eHigh-middle SDI\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e15634 (12142-20283)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e4 (3-5.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.496 (-0.635 - -0.357)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e11578 (9059-15048)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2.9 (2.2-3.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.104 (-1.446 - -0.762)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e558314 (438324-724376)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n 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5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2759 (2187-3436)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.7 (0.6-0.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.165 (-1.37 - -0.96)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2083 (1668-2572)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.5 (0.4-0.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.669 (-2.133 - -1.202)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e100963 (81068-124715)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e27.3 (21.5-34.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.715 (-2.175 - -1.254)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eBoth\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e18393 (14838-23253)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2.4 (1.8-3.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.626 (-0.764 - -0.488)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e13661 (11050-17283)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.8 (1.4-2.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.209 (-1.528 - -0.89)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e659278 (532778-833335)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e86.1 (67-110.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n 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style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e5326 (4852-5889)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.7 (1.5-1.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.996 (-1.096 - -0.895)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e3211 (2932-3535)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1 (0.9-1.2)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.852 (-2.138 - -1.566)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e153718 (141204-168465)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e49.9 (44.7-56.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.833 (-2.132 - -1.532)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1862 (1771-1959)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n 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5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e7188 (6677-7806)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.2 (1.1-1.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.646 (-0.729 - -0.563)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e4341 (4041-4694)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.7 (0.7-0.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.438 (-1.686 - -1.189)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e209167 (195748-225096)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e35.2 (32.3-38.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.411 (-1.71 - -1.112)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:150.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cstrong\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eWHO regions\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:112.55pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:112.95pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width:114.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:150.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eAfrican Region\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e5813 (4537-7592)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2.7 (2-3.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.725 (-0.791 - -0.659)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e5372 (4178-7095)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2.5 (1.9-3.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.755 (-0.861 - -0.649)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e272799 (212823-360219)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e122.5 (92.5-165.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n 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5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.2 (0.9-1.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.875 (-0.927 - -0.823)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2620 (2033-3367)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.1 (0.8-1.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.887 (-1.044 - -0.729)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e138131 (106939-177152)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e56.3 (43.2-73.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.877 (-1.04 - -0.713)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eBoth\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e8645 (6793-11096)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.9 (1.5-2.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.808 (-0.899 - -0.716)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e7992 (6248-10352)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.8 (1.4-2.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.846 (-0.993 - -0.698)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e410930 (321576-532186)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e88.5 (68.4-116.2)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.799 (-0.915 - -0.683)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n 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style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1675 (1364-1985)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.9 (0.7-1.2)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.377 (-0.427 - -0.327)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1509 (1224-1793)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.8 (0.6-1.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.505 (-0.685 - -0.325)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e77617 (62876-92732)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e42.3 (32.9-53.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.44 (-0.709 - -0.169)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eBoth\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e3931 (3389-4579)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1 (0.9-1.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.126 (-0.168 - -0.085)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e3537 (3042-4125)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.9 (0.8-1.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.197 (-0.425 - 0.031)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e178240 (154300-207380)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n 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style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2570 (2417-2726)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1 (0.9-1.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#F4B084;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.56 (0.436 - 0.685)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1863 (1745-1983)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.7 (0.7-0.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0 (-0.462 - 0.465)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e89555 (84036-95170)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e35.1 (32.5-38.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.019 (-0.488 - 0.452)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1139 (1080-1201)\u003c/span\u003e\u003c/p\u003e\n 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style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eBoth\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e3709 (3518-3900)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.7 (0.7-0.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#F4B084;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.504 (0.402 - 0.607)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2730 (2579-2892)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.5 (0.5-0.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.012 (-0.421 - 0.398)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e132120 (125089-139813)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e26.1 (24.5-27.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.028 (-0.432 - 0.377)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:150.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eRegion of the Americas\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2052 (1972-2140)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.8 (0.7-0.8)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#F4B084;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.632 (0.572 - 0.692)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1381 (1319-1444)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.5 (0.5-0.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#F4B084;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.255 (0.05 - 0.46)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e68798 (65856-72026)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e26.1 (24.5-27.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#F4B084;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.3 (0.1 - 0.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1230 (1167-1302)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.4 (0.4-0.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#F4B084;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.573 (0.529 - 0.617)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e910 (858-970)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.3 (0.3-0.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#F4B084;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.348 (0.177 - 0.519)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e45306 (42700-48215)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e16.5 (15.5-17.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#F4B084;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.329 (0.154 - 0.505)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eBoth\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e3282 (3161-3423)\u003c/span\u003e\u003c/p\u003e\n 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(109131-119696)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e21.2 (20.1-22.4)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.201 (-0.215 - 0.619)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width:150.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:center;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eSouth-East Asia Region\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eMale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e7305 (6047-8848)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.3 (1.1-1.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#F4B084;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.103 (0.05 - 0.156)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e6572 (5425-7973)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1.2 (0.9-1.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.013 (-0.262 - 0.29)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e320582 (264532-389286)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e57.6 (46.2-71.9)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.004 (-0.274 - 0.283)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eFemale\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2586 (2087-3074)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.5 (0.4-0.6)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.023 (-0.056 - 0.009)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e2311 (1877-2758)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.4 (0.3-0.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.169 (-0.257 - -0.082)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e117035 (96571-138727)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e21.4 (16.8-26.3)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.173 (-0.262 - -0.084)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:40.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eBoth\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:104.8pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e9891 (8525-11599)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.65pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.9 (0.8-1.1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.55pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.038 (-0.004 - 0.08)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:105.2pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e8884 (7643-10406)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:66.85pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e0.8 (0.7-1)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:112.95pt;background:#BFBFBF;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-0.115 (-0.274 - 0.045)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e437617 (378152-511082)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e39.7 (33.4-47.7)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;background:#BFBFBF;padding:0cm 5.4pt 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style=\"width:112.95pt;border:none;border-bottom:solid windowtext 1.0pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.241 (-1.602 - -0.88)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:143.45pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e1598491 (1299717-2008652)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:97.75pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e146.7 (115.3-186.5)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:114.8pt;border:none;border-bottom:solid windowtext 1.0pt;background:#9BC2E6;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003e-1.187 (-1.492 - -0.881)\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"11\" style=\"width:1115.0pt;border:none;padding:0cm 5.4pt 0cm 5.4pt;height:13.9pt;\"\u003e\n \u003cp style=\"margin:0cm;text-align:left;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-size:13px;font-family:\"Arial\",sans-serif;color:black;'\u003eDALYs, the disability-adjusted life years; ASR, age-standardizedrate; AAPC, average annual percent change; SDI, socio-demographic index; WHO, world health organization.\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"margin:0cm;text-align:justify;font-size:14px;font-family:DengXian;\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Early-onset liver cancer, Global burden of disease study, Incidence, Mortality, Disability adjusted life years","lastPublishedDoi":"10.21203/rs.3.rs-8329191/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8329191/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003eEarly-onset liver cancer (EOLC), occurring in individuals aged 15-49, is an emerging global health challenge. This study aims to assess health inequalities in EOLC burden across regions and sexes and to inform targeted interventions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eUsing Global Burden of Disease (GBD) 2021 data, we analyzed global EOLC incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. Analyses included Joinpoint regression, decomposition, locally estimated scatterplot smoothing (LOESS), and frontier efficiency assessment. Trends to 2050 were projected via a gender-stratified Bayesian age-period-cohort (BAPC) model.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eAbsolute EOLC burden increased globally, though age-standardized rates (ASRs) declined overall. Notably, age-standardized incidence rates (ASIRs) rose among women in high socio-demographic index (SDI) regions and among men in low-middle SDI regions. Hepatitis B virus (HBV) remained the leading cause, but alcohol, hepatitis C virus (HCV), and nonalcoholic steatohepatitis (NASH), especially in young women, showed increasing contributions. Population growth and aging drove increases in the absolute burden. Frontier analysis identified Mongolia as the lowest-performing country, while Somalia, Burundi, and Ethiopia achieved relatively efficient control. The BAPC model projects continued ASR declines by 2050, yet female ASIR is expected to rise modestly due to rising NASH.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eDespite an overall declining EOLC burden, persistent gender and regional inequities and the growing impact of metabolic risks like NASH call for precision public health approaches, including etiology-specific strategies, early screening for high-risk groups (particularly young women), and strengthened health systems in underperforming regions.\u003c/p\u003e","manuscriptTitle":"Trends in global early-onset liver cancer from 1990 to 2050: an analysis of the Global Burden of Disease Study 2021","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-29 08:18:51","doi":"10.21203/rs.3.rs-8329191/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-09T14:04:12+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-05T19:02:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"249747214524251285369725451580564813601","date":"2026-01-30T08:30:14+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-26T16:23:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"270225828884253069388144072549400079523","date":"2026-01-25T05:24:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"191287400630106280989242466037031584684","date":"2026-01-24T16:34:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"28993785779765949459661271705671747381","date":"2026-01-21T15:09:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-26T06:34:10+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-24T05:46:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-17T04:05:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-16T13:12:20+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Oncology","date":"2025-12-16T05:27:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"dion","sideBox":"Learn more about [Discover Oncology](https://www.springer.com/12672)","snPcode":"","submissionUrl":"","title":"Discover Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8c55d712-c416-4bfe-b565-d8f8e61e6a2b","owner":[],"postedDate":"December 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-01T05:40:37+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-29 08:18:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8329191","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8329191","identity":"rs-8329191","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}