Impact of Egypt’s Hepatitis C Elimination Program on Liver Cancer Burden with Projections to 2050

Impact of Egypt’s Hepatitis C Elimination Program on Liver Cancer Burden with Projections to 2050 | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Egypt’s Hepatitis C Elimination Program on Liver Cancer Burden with Projections to 2050 Mohammed Y. Youssef, Mohamed H. Eldesouki, Hazem Abosheaishaa, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8570900/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Primary liver cancer remains a leading cause of cancer-related mortality worldwide, with Egypt representing a uniquely high-burden setting due to historically widespread hepatitis C virus infection. This study aimed to comprehensively evaluate long-term trends in the burden of Primary liver cancer in Egypt from 1990 to 2023, with particular emphasize on the impact of the national HCV elimination campaign, and project future trends through 2050. Methods: Data were obtained from the Global Burden of Disease 2023 database. Age-standardized incidence, mortality, prevalence, and disability-adjusted life years (DALYs) for Primary liver cancer were analyzed by sex and underlying etiology. Future projections to 2050 were generated using the GBD forecasting framework. Results: Between 1990 and 2023, age-standardized incidence, mortality, and DALY rates for PLC in Egypt declined overall, with the steepest reductions observed between 2014 and 2019, coinciding with nationwide HCV eradication efforts. However, a rebound in incidence and mortality was observed after 2019. HCV remained the leading cause of Primary liver cancer mortality throughout the study period, although its contribution declined substantially. Notably, nonalcoholic steatohepatitis surpassed hepatitis B as the second leading cause of Primary liver cancer mortality by 2023. Projections suggest that comprehensive control of viral and metabolic risk factors could reduce Primary liver cancer mortality by nearly half by 2050. Conclusion: Egypt’s HCV elimination campaign substantially reduced the burden of Primary liver cancer; however, long-term surveillance and integrated, multi-etiologic prevention strategies are essential to achieve durable reductions in Primary liver cancer burden. Primary liver cancer Hepatitis C virus Hepatocellular carcinoma Global Burden of Disease Egypt Metabolic liver disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Primary liver cancer (PLC), which is the malignant tumor arising within the liver parenchyma, affects approximately 739,299 new cases worldwide each year ( 1 ). PLC is a pressing global health concern, ranking as the sixth most diagnosed cancer and the third leading cause of cancer-related mortality worldwide. ( 2 ) ( 3 ). Hepatocellular carcinoma (HCC), accounts for approximately 75–86% of primary liver cancer (PLC). The global rise in PLC incidence represents a concerning challenge which underscores the need for targeted prevention, early detection, and robust healthcare infrastructure, particularly in high-burden regions ( 4 ). Egypt represents a uniquely high-risk setting for primary liver cancer, historically bearing one of the highest global burdens of hepatitis C virus (HCV) as one of seven Egyptians have been exposed to HCV by 2008 ( 5 ), a legacy of historical schistosomiasis treatment campaigns ( 6 , 7 ). Additional locally relevant exposures such as Hepatitis B virus (HBV), aflatoxin contamination in food supplies and the rising prevalence of metabolic dysfunction–associated fatty liver disease (MAFLD/NAFLD) driven by increasing obesity and diabetes further compound this risk. The World Health Organization has repeatedly identified Egypt’s viral hepatitis burden as a major public health concern, given its disproportionate contribution to HCC morbidity and mortality in the region. In 2015, Egypt collaborated with the World Health Organization (WHO) to launch a nationwide HCV eradication campaign. The campaign identified more than 1.1 million HCV infections, and 465,922 patients received direct acting antiviral (DAA) ( 8 , 9 ). While Egypt’s nationwide HCV elimination campaign stands as one of the most successful globally, dramatically reducing new infections and improving long-term liver-disease outcomes, the legacy of decades of high transmission continues to influence current HCC incidence ( 10 , 11 ). These factors, alongside limited access to advanced diagnostics and treatments in rural areas, exacerbate the socioeconomic and health impacts of HCC in Egypt ( 12 , 13 ). Worldwide regional disparities in PLC etiology are notable: while HBV and HCV dominate in low- and middle-income settings, alcohol and NAFLD are key drivers in high-income regions ( 14 ). Previous studies have explored global and regional PLC trends, including incidence and mortality predictions, risk factor analyses, and burden assessments up to 2021 ( 15 ). The Global Burden of Disease (GBD) 2021 study reported a global increase in liver cancer prevalence with a slight decline in age-standardized mortality, highlighting significant regional variations ( 16 ). However, national-level analyses for high-burden countries like Egypt are sparse, particularly regarding sex-stratified trends and comprehensive metrics such as disability-adjusted life years (DALYs) ( 17 ). Furthermore, projections beyond 2023 and detailed breakdowns by etiology (e.g., HBV, HCV, NAFLD, alcohol) are lacking, despite Egypt’s ongoing HCV elimination efforts and shifting metabolic risk profiles ( 18 ). This study utilized the GBD 2023 database to systematically analyze the trends of the burden of PLC in Egypt from 1990 to 2023 with risk factor analysis. Analysis was extended by projecting trends to 2050. A further aim was to highlight the impact of Egypt’s HCV elimination campaign on the national burden of primary liver cancer and the critical lessons for other countries with high viral hepatitis burden. Methods Data Source GBD database, developed by international health research collaborations ( 19 ), provides comprehensive estimates of disease, injury, and risk factor effects on health at national and global levels. Data on the age-standardized incidence rate (ASIR), the age-standardized mortality rate (ASMR), the age-standardized Disability-Adjusted Life Year (DALY) of PLC in Egypt were obtained for both sexes between 1990 and 2023. The GBD categorizes PLC etiologies into five groups: HCC due to hepatitis B (HCC-DHB), hepatitis C (HCC-DHC), alcohol use (HCC-DAU), non-alcoholic steatohepatitis (HCC-DNASH), and other causes (HCC-DOC). All estimates are presented with 95% uncertainty intervals (UI). This study adhered to the STROBE reporting guidelines ( 20 ). Statistical Analysis Trends in HCC incidence and mortality by sex and etiology from 1990 to 2023 were analyzed using joinpoint regression. This method identifies time points (“joinpoints”) that segment the timeline into distinct linear trends based on minimizing mean square error. It is widely applied in studying temporal trends in infectious diseases, chronic illnesses, and cancers. Because tumor rates typically follow Poisson distribution, a log-linear model was employed ( 21 ). Models with four joinpoints (five-line segments) were uniformly applied to capture potential trend shifts and facilitate consistent comparisons. Future projections to 2050 were performed using the GBD forecasting framework, which applies mixed-effects regression and autoregressive integrated moving average (ARIMA) models to extend historical disease trends ( 22 ). All analyses were conducted using Joinpoint Regression Software (version 4.9.1.0). Results 1. Overall, Burden of PLC in Egypt 1.1 Mortality Trends The ASMR for PLC in Egypt showed a consistent increase from 1990 to 2023. The age-standardized death rate per 100,000 population decreased from 29.2 (CI: 18.2–43.9) in 1990 to 25.15 (CI:18.35–33.92) by 2023. Males consistently exhibited higher rates than females. In 1990, the age-standardized mortality rate for males was 31 (CI: 16.3–53.7) per 100,000, while females had a rate of approximately 27.7 (CI: 13.7–46.3) per 100,000. By 2023, the ASMR males remained the same of 31.5 (CI: 30.64–46.69) per 100,000 while the ASMR in female declined to 18 (CI: 10.8–29.2) per 100,000 in females (Fig. 1 ) (Table 1 ) Table 1 GBD Comparison: 1990 vs 2023 (Incidence, Prevalence, Mortality, DALYs) EGYPT PLC 1990 2023 Age Incidence Prevalence Deaths DALYs Incidence Prevalence Deaths DALYs Age-standardized 27.972 (17.368–41.848) 29.215 (17.318–43.679) 29.214 (18.211–43.9) 701.919 (435.925–1050.817) 25.12 (18.514–33.807) 26.75 (19.041–36.613) 25.155 (18.351–33.929) 602.133 (436.759–815.864) 15–19 years 0.618 (0.365–0.916) 1.183 (0.64–1.968) 0.433 (0.26–0.625) 31.601 (18.987–45.655) 0.997 (0.592–1.572) 3.267 (1.774–5.271) 0.401 (0.251–0.586) 29.364 (18.409–43.024) 20–24 years 0.904 (0.552–1.337) 1.116 (0.658–1.686) 0.795 (0.49–1.179) 54.041 (33.311–80.114) 1.012 (0.663–1.543) 1.599 (0.965–2.468) 0.732 (0.474–1.077) 49.771 (32.253–73.25) 25–29 years 1.275 (0.774–1.88) 2.117 (1.283–3.127) 0.994 (0.608–1.465) 62.703 (38.38–92.43) 1.283 (0.81–1.85) 2.237 (1.475–3.146) 0.94 (0.595–1.339) 59.254 (37.565–84.436) 30–34 years 2.703 (1.677–4.003) 4.485 (2.742–6.557) 2.009 (1.244–2.979) 116.671 (72.23–173.025) 2.375 (1.586–3.34) 4.01 (2.71–5.735) 1.71 (1.146–2.387) 99.25 (66.453–138.223) 35–39 years 4.807 (2.861–7.02) 7.262 (4.328–10.6) 3.852 (2.295–5.634) 204.487 (121.972–299.253) 3.652 (2.424–5.296) 5.703 (3.805–8.138) 2.825 (1.868–4.077) 149.932 (99.145–216.479) 40–44 years 8.375 (5.216–12.31) 11.97 (7.351–17.682) 7.08 (4.428–10.421) 341.24 (213.228–502.562) 6.455 (4.39–9.349) 9.629 (6.481–13.579) 5.224 (3.557–7.576) 251.487 (171.206–364.541) 45–49 years 19.634 (12.253–29.003) 27.517 (16.159–41.82) 16.754 (10.493–24.838) 724.075 (453.303–1073.582) 13.902 (9.658–19.9) 20.061 (13.873–27.913) 11.417 (7.928–16.307) 493.607 (343.011–705.553) 55–59 years 71.669 (42.691–106.19) 89.138 (52.471–137.234) 65.37 (39.012–96.877) 2204.762 (1314.218–3270.687) 63.154 (44.364–88.353) 78.036 (54.402–112.026) 55.739 (39.119–78.517) 1876.656 (1318.746–2638.719) 60–64 years 105.909 (66.298–158.581) 120.901 (71.717–184.511) 101.56 (63.732–152.259) 2953.878 (1852.487–4430.873) 94.706 (66.747–130.789) 108.094 (73.153–150.503) 87.832 (62.72–120.745) 2550.607 (1823.613–3503.418) 65–69 years 146.994 (92.045–221.241) 154.484 (96.059–229.374) 147.391 (92.7–222.143) 3619.6 (2272.715–5456.583) 147.237 (97.596–212.542) 153.714 (103.634–217.341) 143.377 (95.134–208.464) 3516.195 (2338.972–5102.446) 70–74 years 165.834 (101.751–248.587) 162.89 (99.041–239.9) 173.04 (106.39–259.874) 3506.687 (2157.231–5261.043) 175.913 (119.937–254.383) 169.013 (117.625–240.389) 178.632 (120.654–257.264) 3614.992 (2442.427–5197.264) 75–79 years 198.131 (122.07–301.412) 170.224 (102.313–262.011) 226.07 (140.013–344.653) 3652.993 (2257.439–5560.146) 183.77 (129.097–258.691) 156.579 (105.565–221.99) 203.944 (144.011–287.054) 3302.226 (2336.135–4652.695) 80–84 years 266.195 (155.723–417.439) 181.56 (107.961–274.635) 330.195 (192.272–519.255) 4177.748 (2432.489–6573.692) 205.4 (141.057–282.553) 154.35 (104.495–223.3) 241.675 (170.722–333.875) 3067.712 (2164.005–4230.447) 85–89 years 243.739 (148.455–386.493) 174.316 (99.995–264.912) 333.875 (200.417–530.857) 3367.244 (2020.129–5344.788) 188.896 (130.223–271.405) 131.862 (89.636–185.748) 247.638 (170.722–349.485) 2502.282 (1724.545–3524.455) 90–94 years 231.251 (131.927–348.269) 149.653 (82.727–236.688) 371.152 (211.588–559.583) 3244.003 (1842.291–4868.894) 183.967 (118.806–269.867) 117.964 (79.739–178.142) 292.437 (188.829–429.912) 2558.961 (1660.302–3768.195) 95 + years 207.652 (124.38–322.207) 200.816 (116.791–326.544) 379.316 (227.331–588.504) 3196.446 (1913.019–4953.125) 157.99 (104.31–227.662) 140.926 (85.602–204.192) 286.371 (188.963–413.402) 2408.626 (1590.153–3473.196) Table 2 Age-standardized mortality rates of liver cancer in Egypt by major etiologies in 1990 and 2021. Rates are shown per 100,000 population with 95% uncertainty intervals Cause of Liver Cancer 1990 Male 1990 Female 1990 Both Sexes 2021 Male 2021 Female 2021 Both Sexes Hepatitis B (HBV) 2.10 (1.27–3.66) 1.52 (0.80–2.98) 1.81 (1.06–3.24) 2.83 (1.63–4.44) 1.45 (0.92–2.18) 2.14 (1.27–3.27) Hepatitis C (HCV) 11.93 (8.65–18.85) 11.17 (6.01–21.80) 11.36 (7.35–18.61) 15.78 (11.65–20.45) 10.35 (7.81–13.30) 12.40 (9.31–15.68) Alcohol use 1.44 (0.83–2.59) 0.61 (0.27–1.36) 1.03 (0.57–1.93) 2.58 (1.55–4.18) 0.74 (0.44–1.14) 1.71 (1.03–2.72) NASH 0.93 (0.56–1.63) 1.68 (0.76–3.63) 1.26 (0.66–2.44) 2.35 (1.43–3.51) 3.03 (1.93–4.44) 2.42 (1.50–3.54) Other causes 0.55 (0.32–0.90) 1.07 (0.52–2.26) 0.78 (0.44–1.46) 0.91 (0.54–1.37) 1.28 (0.82–1.87) 1.01 (0.62–1.49) Hepatoblastoma 0.12 (0.07–0.18) 0.14 (0.07–0.23) 0.13 (0.08–0.19) 0.07 (0.05–0.10) 0.05 (0.03–0.06) 0.06 (0.04–0.08) Between 2014 and 2019 there was a steep decline in PLC ASMR where it decreased from 21.86 (CI: 16.7-26.36) to 19.55 (CI: 15.5-24.305), however this is followed by a steep increase afterwards. 1.2 Incidence Trends The age-standardized incidence rate (ASIR) of primary liver cancer (PLC) in Egypt showed a gradual decline from 1990 to 2023. The overall incidence rate per 100,000 population decreased from 28.0 (CI: 17.37–41.85) in 1990 to 25.12 (CI: 18.51–33.81) in 2023. Males consistently exhibited higher incidence rates than females throughout the study period. In 1990, the ASIR among males was 29.63 (CI: 15.67–51.52) per 100,000 compared to 26.50 (CI: 13.23–43.81) per 100,000 among females. While in 2023, the incidence in males slightly increased to 31.50 (CI: 20.93–46.64) per 100,000, in contrast, the incidence among females declined to 18.28 (CI: 10.81–28.75) per 100,000. (Fig. 2 ) Between 2014 and 2019, there was a marked decline in PLC incidence where the ASIR decreased from 27.67 to 23.19 per 100,000, followed by a rebound rise afterwards. 1.3 Prevalence Trends The age-standardized prevalence rate (ASPR) of PLC in Egypt showed a gradual increase from 1990 to 2023. The overall prevalence rate per 100,000 population rose from 15.0 (CI: 9.8–22.5) in 1990 to 22.3 (CI: 15.4–31.8) in 2023. Males consistently exhibited higher prevalence rates than females throughout the study period. In 1990, the ASPR among males was 17.2 (CI: 10.5–26.1) per 100,000 compared to 12.4 (CI: 7.1–20.0) per 100,000 among females. While in 2023, the prevalence in males increased to 25.1 (CI: 17.5–34.9) per 100,000, in contrast, the prevalence among females reached 18.3 (CI: 11.4–26.8) per 100,000. (Fig. 3 ) 1.4 DALYs Trends The age-standardized DALY rate for PLC in Egypt showed a gradual decline from 1990 to 2023. The age-standardized DALY rate per 100,000 population decreased from 701.92 (CI: 435.93–1050.82) in 1990 to 602.13 (CI: 436.76–815.86) by 2023. Males consistently exhibited higher rates than females. In 1990, the age-standardized DALY rate for males was 745.29 (CI: 393.89–1289.69) per 100,000, while females had a rate of approximately 661.04 (CI: 332.73–1089.28) per 100,000. By 2023, the DALY rate in males was 753.60 (CI: 505.16–1117.59) per 100,000 while the DALY rate in females declined to 437.09 (CI: 258.44–692.75) per 100,000 (Fig. 4 Following the same trend as the ASMR and ASIR, there was a significant decline in PLC DALY rates between 2014 and 2019 as it decreased from 526.25 to 473.54 per 100,000, however this is followed by an increase afterwards. 2. Mortality Trends by Underlying Causes The mortality burden of PLC in Egypt is influenced by several key risk factors, most notably viral hepatitis (HBV and HCV), alcohol consumption, and NASH. The following section outlines the trends in mortality attributed to these causes. Liver cancer due to HCV remained the leading cause of PLC mortality throughout the study period, with the death rate decreasing from 18.36 (CI: 11.68–27.75) per 100,000 in 1990 to 14.73 (CI: 9.88–20.68) per 100,000 in 2023. In 1990, HBV was the second leading cause of PLC mortality with a death rate of 3.22 (CI: 1.77–5.31) per 100,000, followed by NASH (2.31, CI: 1.19–3.89), alcohol use (1.79, CI: 0.94–3.09), and hepatoblastoma (0.12, CI: 0.06–0.17). However, by 2012, there was a noticeable epidemiological shift where NASH surpassed HBV as the second leading cause of PLC mortality in Egypt, reflecting the rising burden of metabolic liver disease. By 2023, NASH-related PLC mortality increased to 3.75 (CI: 2.29–5.70) per 100,000, while HBV declined slightly to 3.01 (CI: 1.68–5.17) per 100,000. Alcohol-related liver cancer mortality showed a gradual increase from 1.79 in 1990 to 2.23 per 100,000 in 2023, whereas hepatoblastoma and other causes remained relatively stable with minimal contribution to the overall burden. Between 2014 and 2019, PLC mortality due to HCV markedly decreased from 16.42 to 13.87 per 100,000, likely reflecting the impact of nationwide antiviral therapy programs; however, this decline was offset by a continued rise in NASH-related PLC mortality during the same period. (Fig. 5 ) 3. 2050 projection The 2050 projection shows that following the same trend it is estimated that by 2050 Egypt will have ASMR of 20.11 (CI: 15.20-26.43), with the current scenario while if all the risk factors are controlled including metabolic and vaccination the estimated ASMR will drop to 11.64 (CI: 8.88–15.34) (Fig. 6 ) Discussion Our study findings showed that the ASMR of PLC in Egypt declined continuously reflecting the improvement in health infrastructure and disease awareness, meanwhile this decline is more pronounced between 2015 and 2019 after the implementation of the national HCV eradication campaign, however there is a noticeable rebound after 2019, and the mortality rates increased again. The ASIR and DALY showed a trend parallel to that of the ASMR, with the HCV being the main cause of PLC ( 23 ), or the large reservoir of people with advanced fibrosis prior to HCV treatment, as risk of HCC persists for years post treatment ( 24 ). Also, reinfection remains possible, particularly among high-risk groups such as IV-drug users, dialysis patients, and healthcare workers ( 25 ). Additionally, a small subset of treated patients either did not achieve sustained virologic response or were lost to follow-up ( 26 ). This rebound also could reflect a shift toward more aggressive or advanced hepatocellular carcinoma, particularly among patients with long-standing cirrhosis, resulting in higher mortality and years of life lost despite overall improvements in viral control ( 27 ). Noticeably In recent years, there has been a shift in the underlying risk factors for primary liver cancer, with metabolic risk factors rising sharply. The burden of NASH has shown a steady and sustained increase, overtaking HBV as the second leading cause of PLC in 2023. There have been multiple national initiatives similar to the Egyptian experience. In 2016, Iceland launched a nationwide HCV treatment program, Treatment as Prevention of Hepatitis C (TraP HepC), aimed at elimination of HCV infections ( 28 ). A pre-post pilot study showed a significant improvement in liver stiffness parameters in 92% of patients after treatment of HCV. ( 29 ) The unrestricted access to DAA in Iceland through the Trap HepC initiative led to a rapid drop in the incidence of all cause cirrhosis by 24% between 2016–2022 ( 30 ). Similarly, Taiwan launched a chronic viral hepatitis treatment program in 2003. Studies showed a significant reduction in mortality from chronic liver disease and HCC by 50% between 2004–2018, along with a targeted new HCV elimination initiative was started in 2017.The DAA programs along with the nationwide HBV vaccination campaign led to a significant reduction in chronic liver disease mortality, HCC incidence and HCC mortality in Taiwan ( 31 , 32 ). The 2050 projection is an alarming sign about the growing burden of preventable cases of liver cancer in Egypt where the ASMR could potentially decrease to half the estimated number with more targeted preventative strategies. Strengths of this study include it highlights the unique experience of Egypt that has big epidemiological lessons, which could be an example for other countries for future campaigns, using GBD data which enabled standardized comparisons across time and sexes, a long time-horizon (1990–2023) capturing both pre- and post-DAA eras, and decomposition of burden by key etiologic categories, However, there are several limitations which include reliance on modeled estimates rather than primary registry data for all parameters; potential misclassification under the broad “PLC” category; absence of individual-level data which limits causal inference. The Egyptian experience demonstrates that, nationwide mass screening, and affordable access to antiviral therapy can dramatically reduce viral hepatitis burden, however this should be paralleled with temporal long-term surveillance and multi-etiologic prevention strategies ( 33 ). In conclusion, despite major progress following Egypt’s national HCV elimination campaign, primary liver cancer remains a significant public health concern. The constant decline in incidence, mortality, and DALY rates before 2019 was followed by a rebound likely driven by residual fibrosis-related risk, reinfection, and the growing impact of metabolic liver disease. Targeted prevention and screening strategies, supported by long-term surveillance, early detection, and comprehensive management of both viral and metabolic etiologies are essential to achieve lasting reductions in liver cancer burden Declarations Consent to participate : Not applicable. The study is based solely on data extracted from previously published articles, and no new human participants were involved. Ethics approval : Not applicable. As this is a secondary analysis of published data, no ethical approval was required. Funding : This study did not receive any specific funding from public, commercial, or not-for-profit funding agencies. None of the authors received any financial support in any form. Human Ethics and Consent to Participate declarations : Not applicable. No direct interaction with human participants occurred, and all data were obtained from published sources. Conflict of Interest : The authors declare that they have no conflicts of interest to disclose, including financial, personal, or institutional relationships that could have influenced the work reported in this manuscript. Clinical Trial Number : not applicable Consent to Publish declaration : not applicable Data Availability Statement : All data used in this study are publicly available from the Global Burden of Disease (GBD) Results Tool and the Global Health Data Exchange (GHDx) maintained by the Institute for Health Metrics and Evaluation (IHME). The data are de-identified and accessible at https://vizhub.healthdata.org/gbd-results/ and https://ghdx.healthdata.org/ Corresponding author: Mohammed Y. Youssef, MD Hunt Regional Medical Center 3201 Kari Ln, 472, Greenville, Tx, USA, 75402 Email: [email protected] Phone: +15072717694 References Jiang Z, Zeng G, Dai H, et al. Global, regional and national burden of liver cancer 1990–2021: 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 . AASLD Practice Guidance on Prevention, Diagnosis, and Treatment of Hepatocellular Carcinoma, Singal AG, Llovet JM, Yarchoan M, et al. Hepatology (Baltimore MD). 2023;78(6):1922–65. 10.1097/HEP.0000000000000466 . AASLD Guidelines for the Treatment of Hepatocellular Carcinoma, Heimbach JK, Kulik LM, Finn RS, et al. Hepatology (Baltimore MD). 2018;67(1):358–80. 10.1002/hep.29086 . 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Incidence, Mortality, and Mortality-to-Incidence Ratio Rates Related to Liver Cancer, 1990–2019: A Longitudinal Analysis Based on the Global Burden of Disease Study. MA BMC Public Health. 2022;22(1):604. 10.1186/s12889-022-12867-w . Global, Regional and National Burden of Liver Cancer, Jiang Z, Zeng G, Dai H, et al. BMC Public Health. 2025;25(1):931. 10.1186/s12889-025-22026-6 . Burden of Disease Using Disability Adjusted Life Years in the Middle East and North Africa (MENA), Mathew S, Sherif M, Al-Rifai RH, et al. Region: Protocol of a Systematic Review. BMJ Open. 2025;15(6):e096214. 10.1136/bmjopen-2024-096214 . Global Trend of Aetiology-Based Primary Liver Cancer Incidence, Liu Z, Xu K, Jiang Y, et al. Int J Epidemiol. 2021;50(1):128–42. 10.1093/ije/dyaa196 . From 1990 to 2030: A Modelling Study. Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2023. (GBD 2023) Results. Seattle (WA): Institute for Health Metrics and Evaluation (IHME); 2024. Available from: https://vizhub.healthdata.org/gbd-results/ von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147:573–7. 10.7326/0003-4819-147-8-200710160-00010 . Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med. 2000;19(3):335 – 51. doi: 10.1002/(sici)1097-0258(20000215)19:33.0.co;2-z. Erratum in: Stat Med 2001;20(4):655. PMID: 10649300. Institute for Health Metrics and Evaluation (IHME). GBD Foresight Visualization. Seattle (WA): IHME, University of Washington. 2024. Available from: https://vizhub.healthdata.org/gbd-foresight Bhattacharya D, Aronsohn A, Price J, Lo Re V, AASLD-IDSA HCV Guidance Panel, Hepatitis CG. 2023 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin Infect Dis. 2023 May 25:ciad319. 10.1093/cid/ciad319 . Epub ahead of print. PMID: 37229695. Luna-Cuadros MA, Chen HW, Hanif H, Ali MJ, Khan MM, Lau DT. Risk of hepatocellular carcinoma after hepatitis C virus cure. World J Gastroenterol. 2022;28(1):96–107. 10.3748/wjg.v28.i1.96 . PMID: 35125821; PMCID: PMC8793019. Read P, Tang BZH, Silins E, Doab A, Cornelisse VJ, Gilliver R, Hepatitis C (HCV) Reinfection and Risk Factors among Clients of a Low-Threshold Primary Healthcare Service for People Who Inject Drugs in Sydney, editors. Australia. Viruses 2024, 16, 957. https://doi.org/10.3390/v16060957 van Dijk M, Drenth JPH. HepNed study group. Loss to follow-up in the hepatitis C care cascade: A substantial problem but opportunity for micro-elimination. J Viral Hepat. 2020;27(12):1270–83. 10.1111/jvh.13399 . Epub 2020 Sep 22. PMID: 32964615; PMCID: PMC7693174. De Poli E. Progression of liver disease and associated risk of hepatocellular carcinoma. Hepatoma Res. 2024;10:15. http://dx.doi.org/10.20517/2394-5079.2023.101 . Olafsson S, Tyrfingsson T, Runarsdottir V, Bergmann OM, Hansdottir I, Björnsson ES, Johannsson B, Sigurdardottir B, Fridriksdottir RH, Löve A, Hellard M, Löve TJ, Gudnason T, Heimisdottir M, Gottfredsson M. Treatment as Prevention for Hepatitis C (TraP Hep C) - a nationwide elimination programme in Iceland using direct-acting antiviral agents. J Intern Med. 2018;283(5):500–7. 10.1111/joim.12740 . Epub 2018 Mar 7. PMID: 29512219. Kristjánsson SF, Olafsson S, Gottfredsson M, Love TJ, Björnsson ES. Clinically Important Decrease in Liver Stiffness Following Treatment for Hepatitis C: Outcome of the TraP HepC Nationwide Elimination Program. J Clin Med. 2025;14(11):3982. 10.3390/jcm14113982 . PMID: 40507745; PMCID: PMC12156237. Haraldsson HA, Olafsson S, Gottfredsson M, Benitez Hernandez U, Bjornsson ES. Incidence of cirrhosis in Iceland-impact of the TraP HepC nationwide HCV elimination program. Scand J Gastroenterol. 2024;59(7):835–42. Epub 2024 Apr 27. PMID: 38676467. Chen CJ, Wu CC, Wei SL, Lin LJ, Lee WC, Chiang CJ, Chien RN, Lu SN. National strategy for elimination of liver diseases in Taiwan. J Formos Med Assoc. 2025 Sep 23:S0929-6646(25)00490-5. doi: 10.1016/j.jfma.2025.09.008. Epub ahead of print. PMID: 40993012. Chiang CJ, Jhuang JR, Yang YW, Zhuang BZ, You SL, Lee WC, Chen CJ. Association of Nationwide Hepatitis B Vaccination and Antiviral Therapy Programs With End-Stage Liver Disease Burden in Taiwan. JAMA Netw Open. 2022;5(7):e2222367. 10.1001/jamanetworkopen.2022.22367 . PMID: 35849394; PMCID: PMC92950. Waked, Shebl,Hepatology 2021;, Razavi et al. J Hepatol., Lancet Gastroenterol Hepatol 2020. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Youssef","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIiWNgGAWjYFACHjDJ2ADhycnxszcwMJOixdhYsucAiVoSN8xIwK9Ft7334KebOTayG473GH/8UWGQuEHyjeHnggobBv727gRsWszOnEuWzt2WZrzhzBkzaZ4zBsbbpXOMpWecSWOQOHN2A1YtN3IMgFoOJ264kWPGzNj2R3bnbKAIb9thBgOJXFxajH/nbvsP0mL88ec/A8YNN88Y/yagxQxoywGQFgMJ3gYDxQ03eMzw2wL0gnXutmTjmWeOlUnzHDMABnJamTXPmTQenH4BBtTt3G12sn3Hmzd//FFjAIzKw5tv81TYyPG392LVAgcKB+BMDgMQyYNXOQjIN8CZ7A8Iqh4Fo2AUjIIRBQB9bWrNHYNv2AAAAABJRU5ErkJggg==","orcid":"","institution":"Hunt Regional Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Mohammed","middleName":"Y.","lastName":"Youssef","suffix":""},{"id":587888663,"identity":"dfe24ca4-e5d7-4b03-be35-2644592150f7","order_by":1,"name":"Mohamed H. Eldesouki","email":"","orcid":"","institution":"New York Medical College at Saint Michael’s Medical","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"H.","lastName":"Eldesouki","suffix":""},{"id":587888666,"identity":"2fbb0f06-25ce-42d8-ad2e-15ab70dddcdb","order_by":2,"name":"Hazem Abosheaishaa","email":"","orcid":"","institution":"Brooklyn Hospital Center","correspondingAuthor":false,"prefix":"","firstName":"Hazem","middleName":"","lastName":"Abosheaishaa","suffix":""},{"id":587888668,"identity":"17296eb7-1e82-43d6-912d-69aff0af14d9","order_by":3,"name":"Mohamed Elgozair","email":"","orcid":"","institution":"Danbury Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"","lastName":"Elgozair","suffix":""},{"id":587888669,"identity":"8de1d82b-b3cb-46d0-821c-7d7f879a9c09","order_by":4,"name":"Mahmoud F. Hammad","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Mahmoud","middleName":"F.","lastName":"Hammad","suffix":""},{"id":587888670,"identity":"9beb7a89-eb38-4af1-9d18-60e63f2576e9","order_by":5,"name":"Ahmed Abomhya","email":"","orcid":"","institution":"University of Kentucky","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Abomhya","suffix":""},{"id":587888672,"identity":"4b2a524e-959e-4661-9e03-df64c7cb0104","order_by":6,"name":"Eslam Elhossieny","email":"","orcid":"","institution":"Maimonides Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Eslam","middleName":"","lastName":"Elhossieny","suffix":""},{"id":587888674,"identity":"b6fc8e7a-af28-47c8-a1bb-bfdbea0970f6","order_by":7,"name":"Mona A. Ali","email":"","orcid":"","institution":"Ministry of Health and Population","correspondingAuthor":false,"prefix":"","firstName":"Mona","middleName":"A.","lastName":"Ali","suffix":""},{"id":587888677,"identity":"709203ae-2cbc-454f-a0a9-51a5fb097ec6","order_by":8,"name":"Ehab Faheid","email":"","orcid":"","institution":"Hunt Regional Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ehab","middleName":"","lastName":"Faheid","suffix":""},{"id":587888678,"identity":"b5fcf4ed-f762-42b8-adfc-ad22824381af","order_by":9,"name":"Sherif E Elhanafi","email":"","orcid":"","institution":"Texas Tech University Health Sciences Center El Paso","correspondingAuthor":false,"prefix":"","firstName":"Sherif","middleName":"E","lastName":"Elhanafi","suffix":""}],"badges":[],"createdAt":"2026-01-11 01:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8570900/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8570900/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102245847,"identity":"6385b9a1-b518-4586-a862-b8e21121e319","added_by":"auto","created_at":"2026-02-09 17:56:43","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":279698,"visible":true,"origin":"","legend":"\u003cp\u003eASMR of PLC in Egypt from 1990–2023 for males, females, and both sexes combined, with solid lines showing annual estimates and shaded areas indicating 95% uncertainty intervals.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8570900/v1/198fb5c0b5baa9ddcf280d9d.jpeg"},{"id":102245844,"identity":"2393f720-02ac-44e2-88d2-937529a6fb8f","added_by":"auto","created_at":"2026-02-09 17:56:43","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":280511,"visible":true,"origin":"","legend":"\u003cp\u003eASIR of PLC in Egypt from 1990–2023 for males, females, and both sexes combined, with solid lines showing annual estimates and shaded areas indicating 95% uncertainty intervals.\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8570900/v1/ef7e888cc55e714b3571696f.jpeg"},{"id":102245846,"identity":"4d696aca-82e4-479b-807e-c80db2b05159","added_by":"auto","created_at":"2026-02-09 17:56:43","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":407928,"visible":true,"origin":"","legend":"\u003cp\u003eASPR of PLC in Egypt from 1990–2023 for males, females, and both sexes combined, with solid lines showing annual estimates and shaded areas indicating 95% uncertainty intervals.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8570900/v1/9b625e4b6d2b5c7b56c34814.jpeg"},{"id":102297527,"identity":"afa17f0d-63f0-4613-b7d3-c5f0cbd05240","added_by":"auto","created_at":"2026-02-10 10:28:00","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":296093,"visible":true,"origin":"","legend":"\u003cp\u003eAge-standardized DALY rates for PLC in Egypt from 1990–2023 for males, females, and both sexes combined, with solid lines showing annual estimates and shaded areas indicating 95% uncertainty intervals.\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8570900/v1/2993a7d2289cfa66b8927876.jpeg"},{"id":102245845,"identity":"b130fb96-6095-40e9-adfd-05affdeae39e","added_by":"auto","created_at":"2026-02-09 17:56:43","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":278803,"visible":true,"origin":"","legend":"\u003cp\u003eAge-standardized PLC mortality attributable to major risk factors in Egypt from 1990–2023, with annual estimates and 95% uncertainty intervals shown for HBV, HCV, alcohol use, NASH, other causes, and hepatoblastoma.\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8570900/v1/f577912ee5b9bfa6e1a76e1b.jpeg"},{"id":102245848,"identity":"6a545a55-3850-4b11-9fcf-bb863b2ba605","added_by":"auto","created_at":"2026-02-09 17:56:43","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":133306,"visible":true,"origin":"","legend":"\u003cp\u003eObserved (1990–2023) and projected (2024–2050) age-standardized liver cancer mortality in Egypt, with the dashed line representing the controlled-risk-factor scenario and the solid line representing the reference scenario, and shaded areas indicating uncertainty intervals.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-8570900/v1/b798660764d46e7515500924.png"},{"id":108079405,"identity":"e54d1656-c030-4265-a2c2-2b5f3235681e","added_by":"auto","created_at":"2026-04-29 07:27:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2006782,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8570900/v1/cd58b649-a76f-45dc-9a83-0c04c2ed911a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Impact of Egypt’s Hepatitis C Elimination Program on Liver Cancer Burden with Projections to 2050","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePrimary liver cancer (PLC), which is the malignant tumor arising within the liver parenchyma, affects approximately 739,299 new cases worldwide each year (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). PLC is a pressing global health concern, ranking as the sixth most diagnosed cancer and the third leading cause of cancer-related mortality worldwide. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Hepatocellular carcinoma (HCC), accounts for approximately 75–86% of primary liver cancer (PLC). The global rise in PLC incidence represents a concerning challenge which underscores the need for targeted prevention, early detection, and robust healthcare infrastructure, particularly in high-burden regions (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEgypt represents a uniquely high-risk setting for primary liver cancer, historically bearing one of the highest global burdens of hepatitis C virus (HCV) as one of seven Egyptians have been exposed to HCV by 2008 (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e), a legacy of historical schistosomiasis treatment campaigns (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Additional locally relevant exposures such as Hepatitis B virus (HBV), aflatoxin contamination in food supplies and the rising prevalence of metabolic dysfunction–associated fatty liver disease (MAFLD/NAFLD) driven by increasing obesity and diabetes further compound this risk. The World Health Organization has repeatedly identified Egypt’s viral hepatitis burden as a major public health concern, given its disproportionate contribution to HCC morbidity and mortality in the region. In 2015, Egypt collaborated with the World Health Organization (WHO) to launch a nationwide HCV eradication campaign. The campaign identified more than 1.1\u0026nbsp;million HCV infections, and 465,922 patients received direct acting antiviral (DAA) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). While Egypt’s nationwide HCV elimination campaign stands as one of the most successful globally, dramatically reducing new infections and improving long-term liver-disease outcomes, the legacy of decades of high transmission continues to influence current HCC incidence (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). These factors, alongside limited access to advanced diagnostics and treatments in rural areas, exacerbate the socioeconomic and health impacts of HCC in Egypt (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWorldwide regional disparities in PLC etiology are notable: while HBV and HCV dominate in low- and middle-income settings, alcohol and NAFLD are key drivers in high-income regions (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). Previous studies have explored global and regional PLC trends, including incidence and mortality predictions, risk factor analyses, and burden assessments up to 2021 (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The Global Burden of Disease (GBD) 2021 study reported a global increase in liver cancer prevalence with a slight decline in age-standardized mortality, highlighting significant regional variations (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). However, national-level analyses for high-burden countries like Egypt are sparse, particularly regarding sex-stratified trends and comprehensive metrics such as disability-adjusted life years (DALYs) (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Furthermore, projections beyond 2023 and detailed breakdowns by etiology (e.g., HBV, HCV, NAFLD, alcohol) are lacking, despite Egypt’s ongoing HCV elimination efforts and shifting metabolic risk profiles (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study utilized the GBD 2023 database to systematically analyze the trends of the burden of PLC in Egypt from 1990 to 2023 with risk factor analysis. Analysis was extended by projecting trends to 2050. A further aim was to highlight the impact of Egypt’s HCV elimination campaign on the national burden of primary liver cancer and the critical lessons for other countries with high viral hepatitis burden.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003e \u003cb\u003eData Source\u003c/b\u003e \u003c/p\u003e\u003cp\u003eGBD database, developed by international health research collaborations (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), provides comprehensive estimates of disease, injury, and risk factor effects on health at national and global levels. Data on the age-standardized incidence rate (ASIR), the age-standardized mortality rate (ASMR), the age-standardized Disability-Adjusted Life Year (DALY) of PLC in Egypt were obtained for both sexes between 1990 and 2023. The GBD categorizes PLC etiologies into five groups: HCC due to hepatitis B (HCC-DHB), hepatitis C (HCC-DHC), alcohol use (HCC-DAU), non-alcoholic steatohepatitis (HCC-DNASH), and other causes (HCC-DOC). All estimates are presented with 95% uncertainty intervals (UI). This study adhered to the STROBE reporting guidelines (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eTrends in HCC incidence and mortality by sex and etiology from 1990 to 2023 were analyzed using joinpoint regression. This method identifies time points (“joinpoints”) that segment the timeline into distinct linear trends based on minimizing mean square error. It is widely applied in studying temporal trends in infectious diseases, chronic illnesses, and cancers. Because tumor rates typically follow Poisson distribution, a log-linear model was employed (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eModels with four joinpoints (five-line segments) were uniformly applied to capture potential trend shifts and facilitate consistent comparisons. Future projections to 2050 were performed using the GBD forecasting framework, which applies mixed-effects regression and autoregressive integrated moving average (ARIMA) models to extend historical disease trends (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). All analyses were conducted using Joinpoint Regression Software (version 4.9.1.0).\u003c/p\u003e"},{"header":"Results","content":"\n\u003ch3\u003e1. Overall, Burden of PLC in Egypt\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e1.1 Mortality Trends\u003c/h2\u003e \u003cp\u003eThe ASMR for PLC in Egypt showed a consistent increase from 1990 to 2023. The age-standardized death rate per 100,000 population decreased from 29.2 (CI: 18.2\u0026ndash;43.9) in 1990 to 25.15 (CI:18.35\u0026ndash;33.92) by 2023. Males consistently exhibited higher rates than females. In 1990, the age-standardized mortality rate for males was 31 (CI: 16.3\u0026ndash;53.7) per 100,000, while females had a rate of approximately 27.7 (CI: 13.7\u0026ndash;46.3) per 100,000. By 2023, the ASMR males remained the same of 31.5 (CI: 30.64\u0026ndash;46.69) per 100,000 while the ASMR in female declined to 18 (CI: 10.8\u0026ndash;29.2) per 100,000 in females (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u003cb\u003eGBD Comparison: 1990 vs 2023 (Incidence, Prevalence, Mortality, DALYs)\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003eEGYPT PLC\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e1990\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIncidence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePrevalence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDeaths\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDALYs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIncidence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePrevalence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eDeaths\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDALYs\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge-standardized\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.972 (17.368\u0026ndash;41.848)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.215 (17.318\u0026ndash;43.679)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.214 (18.211\u0026ndash;43.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e701.919 (435.925\u0026ndash;1050.817)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e25.12 (18.514\u0026ndash;33.807)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e26.75 (19.041\u0026ndash;36.613)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e25.155 (18.351\u0026ndash;33.929)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e602.133 (436.759\u0026ndash;815.864)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u0026ndash;19 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.618 (0.365\u0026ndash;0.916)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.183 (0.64\u0026ndash;1.968)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.433 (0.26\u0026ndash;0.625)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.601 (18.987\u0026ndash;45.655)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.997 (0.592\u0026ndash;1.572)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.267 (1.774\u0026ndash;5.271)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.401 (0.251\u0026ndash;0.586)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e29.364 (18.409\u0026ndash;43.024)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u0026ndash;24 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.904 (0.552\u0026ndash;1.337)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.116 (0.658\u0026ndash;1.686)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.795 (0.49\u0026ndash;1.179)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54.041 (33.311\u0026ndash;80.114)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.012 (0.663\u0026ndash;1.543)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.599 (0.965\u0026ndash;2.468)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.732 (0.474\u0026ndash;1.077)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e49.771 (32.253\u0026ndash;73.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25\u0026ndash;29 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.275 (0.774\u0026ndash;1.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.117 (1.283\u0026ndash;3.127)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.994 (0.608\u0026ndash;1.465)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62.703 (38.38\u0026ndash;92.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.283 (0.81\u0026ndash;1.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.237 (1.475\u0026ndash;3.146)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.94 (0.595\u0026ndash;1.339)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e59.254 (37.565\u0026ndash;84.436)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30\u0026ndash;34 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.703 (1.677\u0026ndash;4.003)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.485 (2.742\u0026ndash;6.557)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.009 (1.244\u0026ndash;2.979)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e116.671 (72.23\u0026ndash;173.025)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.375 (1.586\u0026ndash;3.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.01 (2.71\u0026ndash;5.735)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.71 (1.146\u0026ndash;2.387)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e99.25 (66.453\u0026ndash;138.223)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e35\u0026ndash;39 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.807 (2.861\u0026ndash;7.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.262 (4.328\u0026ndash;10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.852 (2.295\u0026ndash;5.634)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e204.487 (121.972\u0026ndash;299.253)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.652 (2.424\u0026ndash;5.296)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.703 (3.805\u0026ndash;8.138)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.825 (1.868\u0026ndash;4.077)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e149.932 (99.145\u0026ndash;216.479)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u0026ndash;44 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.375 (5.216\u0026ndash;12.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.97 (7.351\u0026ndash;17.682)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.08 (4.428\u0026ndash;10.421)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e341.24 (213.228\u0026ndash;502.562)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.455 (4.39\u0026ndash;9.349)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9.629 (6.481\u0026ndash;13.579)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.224 (3.557\u0026ndash;7.576)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e251.487 (171.206\u0026ndash;364.541)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45\u0026ndash;49 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.634 (12.253\u0026ndash;29.003)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.517 (16.159\u0026ndash;41.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.754 (10.493\u0026ndash;24.838)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e724.075 (453.303\u0026ndash;1073.582)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.902 (9.658\u0026ndash;19.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20.061 (13.873\u0026ndash;27.913)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e11.417 (7.928\u0026ndash;16.307)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e493.607 (343.011\u0026ndash;705.553)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e55\u0026ndash;59 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.669 (42.691\u0026ndash;106.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.138 (52.471\u0026ndash;137.234)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.37 (39.012\u0026ndash;96.877)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2204.762 (1314.218\u0026ndash;3270.687)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e63.154 (44.364\u0026ndash;88.353)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e78.036 (54.402\u0026ndash;112.026)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e55.739 (39.119\u0026ndash;78.517)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1876.656 (1318.746\u0026ndash;2638.719)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e60\u0026ndash;64 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e105.909 (66.298\u0026ndash;158.581)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120.901 (71.717\u0026ndash;184.511)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.56 (63.732\u0026ndash;152.259)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2953.878 (1852.487\u0026ndash;4430.873)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e94.706 (66.747\u0026ndash;130.789)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e108.094 (73.153\u0026ndash;150.503)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e87.832 (62.72\u0026ndash;120.745)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2550.607 (1823.613\u0026ndash;3503.418)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e65\u0026ndash;69 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e146.994 (92.045\u0026ndash;221.241)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e154.484 (96.059\u0026ndash;229.374)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e147.391 (92.7\u0026ndash;222.143)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3619.6 (2272.715\u0026ndash;5456.583)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e147.237 (97.596\u0026ndash;212.542)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e153.714 (103.634\u0026ndash;217.341)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e143.377 (95.134\u0026ndash;208.464)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3516.195 (2338.972\u0026ndash;5102.446)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e70\u0026ndash;74 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e165.834 (101.751\u0026ndash;248.587)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e162.89 (99.041\u0026ndash;239.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e173.04 (106.39\u0026ndash;259.874)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3506.687 (2157.231\u0026ndash;5261.043)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e175.913 (119.937\u0026ndash;254.383)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e169.013 (117.625\u0026ndash;240.389)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e178.632 (120.654\u0026ndash;257.264)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3614.992 (2442.427\u0026ndash;5197.264)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e75\u0026ndash;79 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e198.131 (122.07\u0026ndash;301.412)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e170.224 (102.313\u0026ndash;262.011)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e226.07 (140.013\u0026ndash;344.653)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3652.993 (2257.439\u0026ndash;5560.146)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e183.77 (129.097\u0026ndash;258.691)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e156.579 (105.565\u0026ndash;221.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e203.944 (144.011\u0026ndash;287.054)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3302.226 (2336.135\u0026ndash;4652.695)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e80\u0026ndash;84 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e266.195 (155.723\u0026ndash;417.439)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e181.56 (107.961\u0026ndash;274.635)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e330.195 (192.272\u0026ndash;519.255)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4177.748 (2432.489\u0026ndash;6573.692)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e205.4 (141.057\u0026ndash;282.553)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e154.35 (104.495\u0026ndash;223.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e241.675 (170.722\u0026ndash;333.875)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3067.712 (2164.005\u0026ndash;4230.447)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e85\u0026ndash;89 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e243.739 (148.455\u0026ndash;386.493)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e174.316 (99.995\u0026ndash;264.912)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e333.875 (200.417\u0026ndash;530.857)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3367.244 (2020.129\u0026ndash;5344.788)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e188.896 (130.223\u0026ndash;271.405)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e131.862 (89.636\u0026ndash;185.748)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e247.638 (170.722\u0026ndash;349.485)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2502.282 (1724.545\u0026ndash;3524.455)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90\u0026ndash;94 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e231.251 (131.927\u0026ndash;348.269)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e149.653 (82.727\u0026ndash;236.688)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e371.152 (211.588\u0026ndash;559.583)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3244.003 (1842.291\u0026ndash;4868.894)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e183.967 (118.806\u0026ndash;269.867)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e117.964 (79.739\u0026ndash;178.142)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e292.437 (188.829\u0026ndash;429.912)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2558.961 (1660.302\u0026ndash;3768.195)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e95\u0026thinsp;+\u0026thinsp;years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e207.652 (124.38\u0026ndash;322.207)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200.816 (116.791\u0026ndash;326.544)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e379.316 (227.331\u0026ndash;588.504)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3196.446 (1913.019\u0026ndash;4953.125)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e157.99 (104.31\u0026ndash;227.662)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e140.926 (85.602\u0026ndash;204.192)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e286.371 (188.963\u0026ndash;413.402)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2408.626 (1590.153\u0026ndash;3473.196)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAge-standardized mortality rates of liver cancer in Egypt by major etiologies in 1990 and 2021. Rates are shown per 100,000 population with 95% uncertainty intervals\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCause of Liver Cancer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1990 Male\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1990 Female\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1990 Both Sexes\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2021 Male\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2021 Female\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2021 Both Sexes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatitis B (HBV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.10 (1.27\u0026ndash;3.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.52 (0.80\u0026ndash;2.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.81 (1.06\u0026ndash;3.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.83 (1.63\u0026ndash;4.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.45 (0.92\u0026ndash;2.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.14 (1.27\u0026ndash;3.27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatitis C (HCV)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11.93 (8.65\u0026ndash;18.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.17 (6.01\u0026ndash;21.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11.36 (7.35\u0026ndash;18.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e15.78 (11.65\u0026ndash;20.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e10.35 (7.81\u0026ndash;13.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e12.40 (9.31\u0026ndash;15.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.44 (0.83\u0026ndash;2.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.61 (0.27\u0026ndash;1.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.03 (0.57\u0026ndash;1.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.58 (1.55\u0026ndash;4.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.74 (0.44\u0026ndash;1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.71 (1.03\u0026ndash;2.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNASH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.93 (0.56\u0026ndash;1.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.68 (0.76\u0026ndash;3.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.26 (0.66\u0026ndash;2.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.35 (1.43\u0026ndash;3.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.03 (1.93\u0026ndash;4.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.42 (1.50\u0026ndash;3.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther causes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.55 (0.32\u0026ndash;0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.07 (0.52\u0026ndash;2.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.78 (0.44\u0026ndash;1.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.91 (0.54\u0026ndash;1.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.28 (0.82\u0026ndash;1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e1.01 (0.62\u0026ndash;1.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatoblastoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.12 (0.07\u0026ndash;0.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.14 (0.07\u0026ndash;0.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.13 (0.08\u0026ndash;0.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.07 (0.05\u0026ndash;0.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.05 (0.03\u0026ndash;0.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.06 (0.04\u0026ndash;0.08)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBetween 2014 and 2019 there was a steep decline in PLC ASMR where it decreased from 21.86 (CI: 16.7-26.36) to 19.55 (CI: 15.5-24.305), however this is followed by a steep increase afterwards.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e1.2 Incidence Trends\u003c/h2\u003e \u003cp\u003eThe age-standardized incidence rate (ASIR) of primary liver cancer (PLC) in Egypt showed a gradual decline from 1990 to 2023. The overall incidence rate per 100,000 population decreased from 28.0 (CI: 17.37\u0026ndash;41.85) in 1990 to 25.12 (CI: 18.51\u0026ndash;33.81) in 2023.\u003c/p\u003e \u003cp\u003eMales consistently exhibited higher incidence rates than females throughout the study period. In 1990, the ASIR among males was 29.63 (CI: 15.67\u0026ndash;51.52) per 100,000 compared to 26.50 (CI: 13.23\u0026ndash;43.81) per 100,000 among females. While in 2023, the incidence in males slightly increased to 31.50 (CI: 20.93\u0026ndash;46.64) per 100,000, in contrast, the incidence among females declined to 18.28 (CI: 10.81\u0026ndash;28.75) per 100,000. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBetween 2014 and 2019, there was a marked decline in PLC incidence where the ASIR decreased from 27.67 to 23.19 per 100,000, followed by a rebound rise afterwards.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e1.3 Prevalence Trends\u003c/h2\u003e \u003cp\u003eThe age-standardized prevalence rate (ASPR) of PLC in Egypt showed a gradual increase from 1990 to 2023. The overall prevalence rate per 100,000 population rose from 15.0 (CI: 9.8\u0026ndash;22.5) in 1990 to 22.3 (CI: 15.4\u0026ndash;31.8) in 2023.\u003c/p\u003e \u003cp\u003eMales consistently exhibited higher prevalence rates than females throughout the study period. In 1990, the ASPR among males was 17.2 (CI: 10.5\u0026ndash;26.1) per 100,000 compared to 12.4 (CI: 7.1\u0026ndash;20.0) per 100,000 among females. While in 2023, the prevalence in males increased to 25.1 (CI: 17.5\u0026ndash;34.9) per 100,000, in contrast, the prevalence among females reached 18.3 (CI: 11.4\u0026ndash;26.8) per 100,000. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e1.4 DALYs Trends\u003c/h2\u003e \u003cp\u003eThe age-standardized DALY rate for PLC in Egypt showed a gradual decline from 1990 to 2023. The age-standardized DALY rate per 100,000 population decreased from 701.92 (CI: 435.93\u0026ndash;1050.82) in 1990 to 602.13 (CI: 436.76\u0026ndash;815.86) by 2023. Males consistently exhibited higher rates than females. In 1990, the age-standardized DALY rate for males was 745.29 (CI: 393.89\u0026ndash;1289.69) per 100,000, while females had a rate of approximately 661.04 (CI: 332.73\u0026ndash;1089.28) per 100,000. By 2023, the DALY rate in males was 753.60 (CI: 505.16\u0026ndash;1117.59) per 100,000 while the DALY rate in females declined to 437.09 (CI: 258.44\u0026ndash;692.75) per 100,000 (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFollowing the same trend as the ASMR and ASIR, there was a significant decline in PLC DALY rates between 2014 and 2019 as it decreased from 526.25 to 473.54 per 100,000, however this is followed by an increase afterwards.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003e2. Mortality Trends by Underlying Causes\u003c/h3\u003e\n\u003cp\u003eThe mortality burden of PLC in Egypt is influenced by several key risk factors, most notably viral hepatitis (HBV and HCV), alcohol consumption, and NASH. The following section outlines the trends in mortality attributed to these causes.\u003c/p\u003e \u003cp\u003eLiver cancer due to HCV remained the leading cause of PLC mortality throughout the study period, with the death rate decreasing from 18.36 (CI: 11.68\u0026ndash;27.75) per 100,000 in 1990 to 14.73 (CI: 9.88\u0026ndash;20.68) per 100,000 in 2023.\u003c/p\u003e \u003cp\u003eIn 1990, HBV was the second leading cause of PLC mortality with a death rate of 3.22 (CI: 1.77\u0026ndash;5.31) per 100,000, followed by NASH (2.31, CI: 1.19\u0026ndash;3.89), alcohol use (1.79, CI: 0.94\u0026ndash;3.09), and hepatoblastoma (0.12, CI: 0.06\u0026ndash;0.17).\u003c/p\u003e \u003cp\u003eHowever, by 2012, there was a noticeable epidemiological shift where NASH surpassed HBV as the second leading cause of PLC mortality in Egypt, reflecting the rising burden of metabolic liver disease. By 2023, NASH-related PLC mortality increased to 3.75 (CI: 2.29\u0026ndash;5.70) per 100,000, while HBV declined slightly to 3.01 (CI: 1.68\u0026ndash;5.17) per 100,000. Alcohol-related liver cancer mortality showed a gradual increase from 1.79 in 1990 to 2.23 per 100,000 in 2023, whereas hepatoblastoma and other causes remained relatively stable with minimal contribution to the overall burden. Between 2014 and 2019, PLC mortality due to HCV markedly decreased from 16.42 to 13.87 per 100,000, likely reflecting the impact of nationwide antiviral therapy programs; however, this decline was offset by a continued rise in NASH-related PLC mortality during the same period. (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003e3. 2050 projection\u003c/h3\u003e\n\u003cp\u003eThe 2050 projection shows that following the same trend it is estimated that by 2050 Egypt will have ASMR of 20.11 (CI: 15.20-26.43), with the current scenario while if all the risk factors are controlled including metabolic and vaccination the estimated ASMR will drop to 11.64 (CI: 8.88\u0026ndash;15.34) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study findings showed that the ASMR of PLC in Egypt declined continuously reflecting the improvement in health infrastructure and disease awareness, meanwhile this decline is more pronounced between 2015 and 2019 after the implementation of the national HCV eradication campaign, however there is a noticeable rebound after 2019, and the mortality rates increased again. The ASIR and DALY showed a trend parallel to that of the ASMR, with the HCV being the main cause of PLC (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e), or the large reservoir of people with advanced fibrosis prior to HCV treatment, as risk of HCC persists for years post treatment (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Also, reinfection remains possible, particularly among high-risk groups such as IV-drug users, dialysis patients, and healthcare workers (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Additionally, a small subset of treated patients either did not achieve sustained virologic response or were lost to follow-up (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). This rebound also could reflect a shift toward more aggressive or advanced hepatocellular carcinoma, particularly among patients with long-standing cirrhosis, resulting in higher mortality and years of life lost despite overall improvements in viral control (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNoticeably In recent years, there has been a shift in the underlying risk factors for primary liver cancer, with metabolic risk factors rising sharply. The burden of NASH has shown a steady and sustained increase, overtaking HBV as the second leading cause of PLC in 2023.\u003c/p\u003e \u003cp\u003eThere have been multiple national initiatives similar to the Egyptian experience. In 2016, Iceland launched a nationwide HCV treatment program, Treatment as Prevention of Hepatitis C (TraP HepC), aimed at elimination of HCV infections (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA pre-post pilot study showed a significant improvement in liver stiffness parameters in 92% of patients after treatment of HCV. (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) The unrestricted access to DAA in Iceland through the Trap HepC initiative led to a rapid drop in the incidence of all cause cirrhosis by 24% between 2016\u0026ndash;2022 (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Similarly, Taiwan launched a chronic viral hepatitis treatment program in 2003. Studies showed a significant reduction in mortality from chronic liver disease and HCC by 50% between 2004\u0026ndash;2018, along with a targeted new HCV elimination initiative was started in 2017.The DAA programs along with the nationwide HBV vaccination campaign led to a significant reduction in chronic liver disease mortality, HCC incidence and HCC mortality in Taiwan (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe 2050 projection is an alarming sign about the growing burden of preventable cases of liver cancer in Egypt where the ASMR could potentially decrease to half the estimated number with more targeted preventative strategies.\u003c/p\u003e \u003cp\u003eStrengths of this study include it highlights the unique experience of Egypt that has big epidemiological lessons, which could be an example for other countries for future campaigns, using GBD data which enabled standardized comparisons across time and sexes, a long time-horizon (1990\u0026ndash;2023) capturing both pre- and post-DAA eras, and decomposition of burden by key etiologic categories, However, there are several limitations which include reliance on modeled estimates rather than primary registry data for all parameters; potential misclassification under the broad \u0026ldquo;PLC\u0026rdquo; category; absence of individual-level data which limits causal inference.\u003c/p\u003e \u003cp\u003eThe Egyptian experience demonstrates that, nationwide mass screening, and affordable access to antiviral therapy can dramatically reduce viral hepatitis burden, however this should be paralleled with temporal long-term surveillance and multi-etiologic prevention strategies (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn conclusion, despite major progress following Egypt\u0026rsquo;s national HCV elimination campaign, primary liver cancer remains a significant public health concern. The constant decline in incidence, mortality, and DALY rates before 2019 was followed by a rebound likely driven by residual fibrosis-related risk, reinfection, and the growing impact of metabolic liver disease. Targeted prevention and screening strategies, supported by long-term surveillance, early detection, and comprehensive management of both viral and metabolic etiologies are essential to achieve lasting reductions in liver cancer burden\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e: Not applicable. The study is based solely on data extracted from previously published articles, and no new human participants were involved.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e: Not applicable. As this is a secondary analysis of published data, no ethical approval was required.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This study did not receive any specific funding from public, commercial, or not-for-profit funding agencies. None of the authors received any financial support in any form.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations\u003c/strong\u003e: Not applicable. No direct interaction with human participants occurred, and all data were obtained from published sources.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e: The authors declare that they have no conflicts of interest to disclose, including financial, personal, or institutional relationships that could have influenced the work reported in this manuscript.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e: not applicable\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eConsent to Publish declaration\u003c/strong\u003e: not applicable\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e: All data used in this study are publicly available from the Global Burden of Disease (GBD) Results Tool and the Global Health Data Exchange (GHDx) maintained by the Institute for Health Metrics and Evaluation (IHME). The data are de-identified and accessible at https://vizhub.healthdata.org/gbd-results/ and https://ghdx.healthdata.org/\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMohammed Y. Youssef, MD\u003c/p\u003e\n\u003cp\u003eHunt Regional Medical Center\u003c/p\u003e\n\u003cp\u003e3201 Kari Ln, 472,\u003c/p\u003e\n\u003cp\u003eGreenville, Tx, USA, 75402\u003c/p\u003e\n\u003cp\u003eEmail: [email protected]\u003c/p\u003e\n\u003cp\u003ePhone: +15072717694\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJiang Z, Zeng G, Dai H, et al. Global, regional and national burden of liver cancer 1990\u0026ndash;2021: a systematic analysis of the global burden of disease study 2021. 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JAMA Netw Open. 2022;5(7):e2222367. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamanetworkopen.2022.22367\u003c/span\u003e\u003cspan address=\"10.1001/jamanetworkopen.2022.22367\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 35849394; PMCID: PMC92950.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWaked, Shebl,Hepatology 2021;, Razavi et al. J Hepatol., Lancet Gastroenterol Hepatol 2020.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Primary liver cancer, Hepatitis C virus, Hepatocellular carcinoma, Global Burden of Disease, Egypt, Metabolic liver disease","lastPublishedDoi":"10.21203/rs.3.rs-8570900/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8570900/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction:\u003c/strong\u003e\u003cbr\u003e\nPrimary liver cancer remains a leading cause of cancer-related mortality worldwide, with Egypt representing a uniquely high-burden setting due to historically widespread hepatitis C virus infection. This study aimed to comprehensively evaluate long-term trends in the burden of Primary liver cancer in Egypt from 1990 to 2023, with particular emphasize on the impact of the national HCV elimination campaign, and project future trends through 2050.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003cbr\u003e\nData were obtained from the Global Burden of Disease 2023 database. Age-standardized incidence, mortality, prevalence, and disability-adjusted life years (DALYs) for Primary liver cancer were analyzed by sex and underlying etiology. Future projections to 2050 were generated using the GBD forecasting framework.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003cbr\u003e\nBetween 1990 and 2023, age-standardized incidence, mortality, and DALY rates for PLC in Egypt declined overall, with the steepest reductions observed between 2014 and 2019, coinciding with nationwide HCV eradication efforts. However, a rebound in incidence and mortality was observed after 2019. HCV remained the leading cause of Primary liver cancer mortality throughout the study period, although its contribution declined substantially. Notably, nonalcoholic steatohepatitis surpassed hepatitis B as the second leading cause of Primary liver cancer mortality by 2023. Projections suggest that comprehensive control of viral and metabolic risk factors could reduce Primary liver cancer mortality by nearly half by 2050.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003cbr\u003e\nEgypt’s HCV elimination campaign substantially reduced the burden of Primary liver cancer; however, long-term surveillance and integrated, multi-etiologic prevention strategies are essential to achieve durable reductions in Primary liver cancer burden.\u003c/p\u003e","manuscriptTitle":"Impact of Egypt’s Hepatitis C Elimination Program on Liver Cancer Burden with Projections to 2050","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-09 17:56:38","doi":"10.21203/rs.3.rs-8570900/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"702c4ad4-30cd-4d27-871b-5a3b05a8dc5f","owner":[],"postedDate":"February 9th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Withdrawn","date":"2026-04-29T07:19:20+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-29T07:26:48+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-09 17:56:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8570900","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8570900","identity":"rs-8570900","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}