Temporal Trends in Prevalence of Chronic Liver Disease among Women of Childbearing Age from 1992 to 2021

Temporal Trends in Prevalence of Chronic Liver Disease among Women of Childbearing Age from 1992 to 2021 | 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 Article Temporal Trends in Prevalence of Chronic Liver Disease among Women of Childbearing Age from 1992 to 2021 Hedan Chen, Hongwei Wu, Jiansheng Zhu, Junyan Liu, Ali Li, Weiti Wu, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5594401/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background Chronic liver disease (CLD) is among the foremost contributors to global mortality. This investigation attempted to profoundly analyze temporal trends in CLD prevalence among women of childbearing age (WCBA) over a span of 30 years. Methods An age-period-cohort (APC) model was constructed to determine the overall annual percentage change (net drift [ND], % per year) and annual percentage change within discrete age brackets (local drift, % per year) in CLD prevalence from 1992 to 2021. The APC model accommodates longitudinal age-specific rates while adjusting for deviations across periods from 1992 to 2021 (age effects), as well as period/cohort relative risks (period/cohort effects). Results From 1992 to 2021, the global ND in CLD prevalence among WCBA was 0.057% per year (95% confidence interval [CI]: 0.029%-0.084%), varying across regions (from − 0.27–0.66%). From the local drift perspective, age groups with increasing prevalence were more prevalent in high SDI region (SDIR), while those with decreasing were more common in low SDIR. Age effects showed a consistent patterns across different SDIRs, with an incremental rise in risk associated with advancing age. Period risks were relatively lower in low SDIR, while other regions demonstrated more adverse period risks. Furthermore, across birth cohorts, improvements in prevalence were observed in all regions. Conclusion Over the past 30 years, the global prevalence of CLD among WCBA has demonstrated a predominantly adverse trend. Strategic advancements in prevention, management, and treatment of CLD could mitigate relative risks for successive birth cohorts. Health sciences/Gastroenterology/Hepatology Health sciences/Medical research/Epidemiology Age-period-cohort model Chronic liver disease Global Burden of Disease Sociodemographic index Temporal trend Women of childbearing age Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Cirrhosis and chronic liver disease (hereafter referred to as CLD) can arise from various etiologies, primarily including hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, excessive alcohol consumption, and non-alcoholic fatty liver disease (NAFLD) 1 . CLD ranks among the top ten causes of global mortality 2 . Despite the decline in HBV incidence following vaccination programs 3 , the incidence of NAFLD and alcoholic liver disease (ALD) is on the rise, with the overall prevalence of CLD expected to escalate in the foreseeable future 4 . The World Health Organization (WHO) characterizes WCBA as women aged 15–49 years, a demographic that constitutes approximately one-quarter of the global population. With a global fertility rate of 2.4 children per woman, the health status of women within this age group is closely tied to the well-being of newborns 5 . As the incidence of liver disease continues to rise among WCBA, a concomitant increase in pregnancies in this demographic is noteworthy. Research indicates that the delivery rate among women with cirrhosis has nearly doubled over two decades 6 . CLD significantly and adversely affects maternal morbidity and mortality 7 . Women with CLD are more likely to give birth to infants with low birth weight or preterm birth. Up to two-thirds of pregnant women with CLD may experience preterm birth, with deliveries before 30 weeks occurring in one-fifth of such pregnancies 8 . Pregnant women diagnosed with NAFLD face an elevated risk of developing gestational diabetes and preeclampsia 9 . While there are numerous studies on the prevalence of CLD in specific age groups, there is a lack of information on the trends of CLD prevalence among WCBA and particularly in relation to age, period, and birth cohort effects. The study extracted data on CLD among WCBA from GBD 2021 and utilized an APC model to analyze the temporal trends in CLD prevalence from 1992 to 2021 globally, regionally, and nationally. Methods Data Source The GBD 2021 study, released in 2024, includes health and disease data from 1980 to 2021. It provides epidemiological assessments of 371 diseases and injuries across 204 countries and regions, with continuous data updates 10 . Extensive information on data inputs, processing methodologies, synthesis procedures, and final models are accessible in the associated GBD 2021 publications 10 . The GBD network employed standardized Bayesian tools to integrate a vast array of data spanning time periods, age groups, geographical locations, and health conditions, enabling precisely estimation of disease burden. This methodology allows to estimate in countries lacking primary data sources by "borrowing" information from existing data, enabling comprehensive estimates of chronic disease burden globally. The SDI, derived from overall fertility rates for women under 25 years, average years of education for women aged 15 and above, and per capita income, is used to measure a country's or region's development level. Each country was categorized into five SDI quintiles based on the 2021 SDI value: low, low-middle, middle, high-middle, and high. We extracted the prevalence of CLD among WCBA in 204 countries and regions, categorized by SDI. All rates were per 100,000 population. The 95% uncertainty intervals (UIs) were defined using the 25th and 975th values of 1,000 ordered posterior distributions based on GBD algorithms 11 . Analysis of Temporal Trends in CLD Prevalence among WCBA We examined temporal trends in CLD prevalence among WCBA from 1992 to 2021, utilizing case numbers and age-standardized (AS) rates. AS prevalence rates were derived through direct age standardization, assuming rates follow the weighted sum of independent Poisson random variables. The relative distribution of CLD prevalence was figured out across seven distinct age group (45–49, 40–44, 35–39, 30–34, 25–29, 20–24, and 15–19 years) among WCBA and the changes in prevalence age distribution over time were analyzed. The APC model is commonly employed to investigate the distinct contributions of age, period, and cohort effects on the prevalence and mortality of chronic diseases 12 . In this study, the APC model was employed to examine temporal trends in prevalence, stratified by age, period, and birth cohort 13 . Given the complete linear relationship among age, period, and cohort, model identifiability becomes problematic. To resolve this issue, we derived estimable APC parameters and functions while avoiding arbitrary constraints in the model 13 . Detailed methodologies of the APC model have been discussed elsewhere 14 . In this investigation, estimates of CLD prevalence among WCBA and corresponding population data from the GBD 2021 dataset were utilized as foundational inputs into the APC model. In our analysis, focusing on WCBA (15–49 years), we employed seven distinct age groups (45–49, 40–44, 35–39, 30–34, 25–29, 20–24, and 15–19 years). This age segmentation ensures alignment with the requisite five-year age intervals corresponding to five-year calendar periods, a fundamental requirement for the APC model. By adhering to these specifications, we aimed to capture comprehensive insights into how CLD prevalence evolves across different stages of reproductive age, thereby illuminating potential avenues for targeted intervention and policy formulation. Correspondingly, the study period (1992–2021) was divided into six five-year periods: 1992–1996, 1997–2001, 2002–2006, 2007–2011, 2012–2016, and 2017–2021. Thus, 12 partially overlapping 10-year birth cohorts were used: 1942–1951, 1947–1956, 1952–1961, 1957–1966, 1962–1971, 1967–1976, 1972–1981, 1977–1986, 1982–1991, 1987–1996, 1992–2001, and 1997–2006. The APC model also estimates the overall annual percentage change in prevalence (ND, % per year) and he annual percentage change in prevalence within specific age groups (local drift, % per year). This reflects trends influenced by birth cohort effects 14 . The significance of these annual percentage changes was figured out through Wald χ 2 test 14 . In the APC model, the age effects were represented by fitted longitudinal age-specific rates adjusted for period deviations. The period and cohort influences were elucidated by the computation of period/cohort relative risks, which formulated as the ratios of prevalence rates associated with specific ages across each period/cohort relative to an arbitrarily selected reference period/cohort. It is noteworthy that the utilization of this reference period/cohort was inherently arbitrary and exerted no influence on the analytical robustness of the outcomes. It was attempted to process and visualize data through R 4.3.1 software. P-values < 0.05 indicated statistical significance. Results Trends in CLD prevalence in WCBA, 1992–2021 The global and regional prevalence rates of CLD, AS prevalence rates, and NDs were shown in Table 1 . From 1992 to 2021, the global prevalence of CLD among WCBA surged by 53.42%, resulting in 413.67 million cases (95% UI: 377.66-459.28) in 2021, a reflection of the growing global population. The percentage variation in CLD prevalence was elevated across all SDIRs. In 2021, the global age-standardized prevalence rate of CLD among WCBA was 20,877.84 per 100,000 (95% UI: 17,250.33-25,044.54), an increase of 4.4% from 1992. Relative increases in age-standardized prevalence rate were observed in low-middle, high-middle, and high SDIRs. The APC model further estimated a global ND in CLD prevalence among WCBA at 0.057% per year (95% CI: 0.029%-0.084%), varying from − 0.27% (95% CI: -0.32% to -0.23%) in middle SDIR to 0.66% (95% CI: 0.62%-0.70%) in high SDIR. National prevalence rates and age-standardized prevalence rates of CLD among WCBA in 2021 and NDs of prevalence trends from 1992 to 2021 were demonstrated in Fig. 1 and online supplemental table S1 . In 2021, 66 countries and regions had a CLD prevalence of at least 1 million, with China, India, Indonesia, Nigeria, and Brazil accounting for 47.35% of the global CLD prevalence among WCBA. In 103 countries, age-standardized prevalence rates reached at least the global average, with 21 countries, including Egypt, Qatar, and Kuwait, exceeding 1.5 times the global average prevalence, most of which were high and high-middle SDI countries. From 1992 to 2021, the United Arab Emirates had the highest increase in age-standardized prevalence (25.91%), with an annual ND of 0.92% (95% CI: 0.89%-0.94%). Age-standardized prevalence rates have declined in 90 countries. Although China and India had the highest CLD prevalence due to their large populations, their age-standardized prevalence rates decreased, with relatively minor changes in ND. Among the 204 countries and regions, the APC model estimated ND trends indicating an upward trend in 99 countries and regions, a downward trend in 86 countries, and a relatively stable trend in 19 countries, demonstrating strong heterogeneity in CLD prevalence trends globally. The annual percentage change in age-specific prevalence of CLD among WCBA, calculated by the APC model as local drifts was presented in Fig. 2 A and online supplemental table S2. Globally, the prevalence of CLD among WCBA declined in the 15–19 and 20–24 age groups but increased from the 30–34 to 45–49 age groups. The decline in the 15–19 and 20–24 age groups diminished with age. The prevalence of CLD in adolescents (15–19 years) showed a declining trend across all SDIRs, with the steepest decline in high-middle SDIR (-1.66%, 95% CI: -1.41% to -1.91%) and the smallest decline in high SDIR (-0.24%, 95% CI: -0.11% to -0.36%). Moreover, in high SDIR, prevalence increased in all age groups except 15–19 years. The local drifts in CLD prevalence for each age group across different countries were shown in online supplemental table S3. The temporal changes in age distribution of CLD prevalence among WCBA were shown in Fig. 2 B. Globally, CLD prevalence transitioned from 15–19 years to 20–49 years, a trend evident across all SDIR except low SDI. Additionally, older age groups represented a larger share of the prevalence, with over 50% of CLD prevalence in 2021 concentrated among women aged 35 years and older in all regions except low and low-middle SDIRs. Composition of CLD Causes among WCBA from 1992 to 2021 across Different SDI Regions In all five SDIRs, NAFLD consistently constituted the largest proportion of CLD, accounting for over 50% of all liver diseases (Fig. 3 ). Globally, the prevalence of HBV declined, whereas NAFLD significantly increased, rising from 61.11% in 1992 to 74.24% in 2021, while HBV decreased from 27.34–17.26%. This trend was consistent across all SDIR. HCV showed a slow decline globally and across SDIR, but in low SDIR, the decrease in HBV and increase in NAFLD were relatively moderate (HBV from 32.63% in 1992 to 29.81% in 2021, and NAFLD from 50.60% in 1992 to 59.19% in 2021). The proportion of ALD cases showed relatively minor changes, decreasing from 0.057% in 1992 to 0.052% in 2021 (online supplemental table S4). Age, period and birth cohort effects on CLD prevalence in WCBA Age, period, and birth cohort effects derived from the APC model were shown in Fig. 4 and online supplemental tables S5-S7. Age effects demonstrated uniform patterns across diverse SDIRs, exhibiting a minimal risk in the 15-19-year group that progressively elevated with advancing age. Specifically, high SDIRs consistently reported lower overall prevalence rates among all age-based groups relative to their lower SDI counterparts. Period effects revealed a remarkable trend: the prevalence initially attenuated before rising across most SDIRs, with notable exceptions in high and low SDIRs. During the study period, all regions except high and low SDIRs had more adverse period risks in most periods. In high SDIR, the risk increased gradually over time, while in low SDIR, the risk decreased gradually in later periods and stabilized thereafter. When comparing the 2017–2021 period to the reference period of 2007–2011, the relative period risk was 1.098 (95% CI: 1.086–1.110) in high SDIRs, 1.054 (95% CI: 1.034–1.075) in high-middle SDIRs, 1.036 (95% CI: 1.022–1.050) in middle SDIRs, and 0.997 (95% CI: 0.993-1.000) in low SDIRs. Regarding birth cohort effects, the prevalence risk for successive birth cohorts globally initially increased and then decreased, with overall improvements in prevalence across all SDIRs for successive birth cohorts. Relative to individuals born in the 1982–1991 cohort, the relative cohort risk for those form the 1997–2006 cohort was 0.836 (95% CI: 0.828–0.844) in low-middle SDIR and 0.908 (95% CI: 0.872–0.945) in high SDIR. The influence of age, period, and birth cohort on CLD prevalence among WCBA in each country was presented in online supplemental tables S8-S10. The temporal trends in global CLD prevalence, highlighting several typical countries with relatively favorable and unfavorable age, period, and birth cohort effects across different SDI quintiles were illustrated in Fig. 5 . The United States, a high SDI country, demonstrated unfavorable trends, with no observed decline in prevalence across all age groups in recent years, and worsening period and cohort risks. In contrast, Australia showed more favorable trends in cohort risks among high SDI countries. China and Spain serve as examples of high-middle SDI countries, demonstrating a transition in prevalence from adolescence to adulthood. In both China and Spain, the prevalence rates among the elderly population were rising. China showed an early decline in risk followed by an increase in later stages, while Spain exhibited a sustained increase, and the birth cohort risks in both countries tended to decrease in later stages. Among low SDI countries, Sierra Leone and the Central African Republic showed declining prevalence across all age groups, with period risks initially decreasing then increasing, and gradually decreasing cohort risks. Discussion Globally, CLD stands as a profound determinant of morbidity and mortality, and 2 million deaths are attributed to liver disease annually 15 . CLD can lead to severe complications and death, significantly impacting quality of life and imposing a substantial economic burden 16 . Despite various conditions leading to CLD, HBV, HCV, NAFLD, and ALD are the most common culprits 17 . In 2015, the United Nations established defined objectives under Sustainable Development Goal 3, with a target to decrease the global maternal mortality ratio to less than 70 per 100,000 live births by 2030 18 . In comparison to the broader obstetric population, expectant mothers with CLD confront elevated risks of adverse outcomes affecting both maternal health and fetal well-being. These include gestational hypertension, gestational diabetes, preeclampsia, preterm birth, and low birth weight 6 , 7 . Such severe complications not only pose significant challenges to maternal survival but also impede progress towards achieving the United Nations' Sustainable Development Goals. This study explored the relative influence of age, period, and birth cohort on the prevalence trends of CLD among WCBA. Age effects demonstrated consistent patterns across various SDIRs, with risks escalating with advancing age. This is understandable, as CLD develops over time due to continuous damage to liver cells, and prolonged exposure to risk factors with age ultimately leads to CLD 19 . Globally, we observed adverse period effects and favorable birth cohort effects. CLD period effects have been rising over the past decade. Period effects reflect changes in incidence or mortality rates due to societal, economic, cultural, or environmental changes 20 . Over time, with improvements in socio-economic conditions, education, and living standards, the overall incidence of CLD has increased. Recent studies indicated that the rising prevalence of CLD is mainly driven by the increasing prevalence of NAFLD 21 . The global prevalence of obesity and type 2 diabetes is a major contributor to the rising prevalence and progression of NAFLD 22 . Factors such as increased calorie intake, dietary changes, reduced physical activity levels, and alterations in gut microbiota contribute to this trend 23 . Air pollution has also recently been identified as a potential risk factor for liver disease 24 . Future health education on NAFLD and the promotion of healthy lifestyles and dietary habits for individuals over 30 years old are recommended 4 . It is encouraging to note that the prevalence of HBV is declining. With improved access to HBV vaccines globally, implementation of mother-to-child transmission prevention programs, and approval of antiviral medications for children and adolescents, the incidence of chronic viral hepatitis has significantly reduced 25 , 26 . This is consistent with our findings, although the decline was slower in low SDIR. In low SDIR, limited access to antiviral medications 27 , challenges in standardizing screening and diagnosis, and low HBV vaccine coverage exacerbate the prevention and treatment burden of liver diseases among WCBA 28 . As of 2016, nearly half of children aged 1 to 6 in India had not been administered the hepatitis B vaccine 29 . Expanding screening for HBV, increasing vaccine coverage, and improving access to antiviral drugs are crucial in these regions. Regarding birth cohort effects, individuals born after 1980–1989 generally exhibited lower risks than those born earlier, consistent with the introduction and widespread use of HBV vaccines. In the 1980s and 1990s, many countries adopted this vaccine 30 . The WHO recommends routine HBV immunization for newborns globally and has been promoting the inclusion of HBV vaccines in national immunization programs since 1992. Surveys indicated that between 1990 and 2019, the prevalence of HBV surface antigen among infants and children aging under five years old declined by 77% 3 . Additionally, with social progress, significant improvements in healthcare services for newborns have been observed. Firstly, it describes the prevalence trends of CLD among WCBA, but significant socio-economic and clinical changes worldwide over the past three decades may have altered the impact of each type of CLD, which this article does not detail. Secondly, in some underdeveloped countries with lower healthcare standards, misdiagnosis and underdiagnosis of diseases may lead to underestimation. The GBD collaborators use extensive statistical modeling methods, which may affect the accuracy of age, period, and birth cohort effect estimates. Thirdly, the lagging nature of GBD data should be noted. In summary, nearly half of the countries worldwide were experiencing an upward trend in CLD. Concurrently, worsening risks in many countries indicated a significant shortfall in resources allocated to WCBA CLD healthcare. It is noteworthy that while HBV is declining, NAFLD is rapidly increasing. Abbreviations ALD alcoholic liver disease APC age-period-cohort AS age-standardized CI confidence interval CLD chronic liver disease GBD Global Burden of Disease HBV hepatitis B virus HCV hepatitis C virus NAFLD non-alcoholic fatty liver disease ND net drift SDI sociodemographic index UI uncertainty interval WCBA women of childbearing age WHO World Health Organization. Declarations Funding This investigation was made possible through the financial backing provided by the Key Research and Development Project of Zhejiang Province (2023C03046) and further bolstered by the Taizhou Science and Technology Program (1901ky14). Contributors H.D.C and H.W.W were instrumental in conceptualizing and designing the study, as well as in acquiring the raw data, conducting the analysis, and preparing the visual representations. The initial drafting of the manuscript was undertaken by H.D.C. H.W.W, A.L.L, and J.Y.L provided in-depth critical review and revisions. Y.H.L, L.L, N.Z, and Y.C contributed to data collection, analysis, and visualization. Y.Z.T, H.S, and W.T.W oversaw the final manuscript preparation. All authors, who engaged in this investigation, granted their approval of the final manuscript, and endorsed its submission. H.S assumes ultimate responsibility as the guarantor for the overall integrity of the content. Competing interests The authors affirmed the absence of competing interest. Ethics approval The University of Washington’s Institutional Review Board has authorized a waiver of informed consent for the utilization of deidentified data in the GBD study. Data availability Data of the study are accessible via the Institute for Health Metrics and Evaluation (IHME)’s online platform, found at https://vizhub.healthdata.org/gbd-results/. References Kulik, L. & El-Serag, H. B. Epidemiology and Management of Hepatocellular Carcinoma. Gastroenterology 156 , 477-491 e471, doi:10.1053/j.gastro.2018.08.065 (2019). Asrani, S. 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Tables Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Supplementaryfiles.pdf Table1GlobalandregionalprevalenceratesofCLDamongWCBA.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 04 Mar, 2025 Reviews received at journal 25 Feb, 2025 Reviewers agreed at journal 25 Feb, 2025 Reviewers invited by journal 24 Feb, 2025 Editor assigned by journal 17 Feb, 2025 Editor invited by journal 20 Dec, 2024 Submission checks completed at journal 19 Dec, 2024 First submitted to journal 06 Dec, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5594401","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":392958466,"identity":"a35f378b-db5f-4acb-bbbb-f27f82308d4f","order_by":0,"name":"Hedan Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYDACCQYGZjBib2x8kFAhISdPvBaew4cNHpyxMDZsIFqLRFqa5MO2ikSGAwR08M9uPva4oMJa3pwhx0AicZ5EAmMD88NHN/BZcudYuvGMM+mGOxvOGBgkbpPIY2dgMzbOwaPFQCLHTJq37TDjhoM9BglALcWMDTxs0vi15H+T5v132H7DYR6DA4lzJBIbDhDUksMmzdtwOHHDMbbEhsQGIrRI3Egzk+Y5lp684QzzYYaEYxLGhs0E/MI/I/mZNE+Nte2G+w/bf/6oqZOTZ29++BifFiyAmTTlo2AUjIJRMAqwAADhlEx5DYex5wAAAABJRU5ErkJggg==","orcid":"","institution":"Affiliated Taizhou Hospital of Wenzhou Medical University","correspondingAuthor":true,"prefix":"","firstName":"Hedan","middleName":"","lastName":"Chen","suffix":""},{"id":392958467,"identity":"65b254b8-c661-402e-8acd-52d386f6ce28","order_by":1,"name":"Hongwei Wu","email":"","orcid":"","institution":"Taizhou Enze Medical Center (Group) Enze Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hongwei","middleName":"","lastName":"Wu","suffix":""},{"id":392958468,"identity":"bbc1aa05-375f-4dc5-b560-29f182f4e60d","order_by":2,"name":"Jiansheng Zhu","email":"","orcid":"","institution":"Affiliated Taizhou Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jiansheng","middleName":"","lastName":"Zhu","suffix":""},{"id":392958469,"identity":"2fb90e44-7f6c-443b-878e-4d2509939d2e","order_by":3,"name":"Junyan Liu","email":"","orcid":"","institution":"Affiliated Taizhou Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Junyan","middleName":"","lastName":"Liu","suffix":""},{"id":392958470,"identity":"0df4f0de-a243-48f7-a6ea-51db763c9566","order_by":4,"name":"Ali Li","email":"","orcid":"","institution":"Affiliated Taizhou Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ali","middleName":"","lastName":"Li","suffix":""},{"id":392958471,"identity":"b5a09cfb-a988-4a77-a2af-14fe8f5442a0","order_by":5,"name":"Weiti Wu","email":"","orcid":"","institution":"Affiliated Taizhou Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Weiti","middleName":"","lastName":"Wu","suffix":""},{"id":392958472,"identity":"dd7ad409-618a-48b7-91a6-9896017a8290","order_by":6,"name":"Ling Lin","email":"","orcid":"","institution":"Affiliated Taizhou Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ling","middleName":"","lastName":"Lin","suffix":""},{"id":392958473,"identity":"4ffa0d5e-fa3e-42ac-8f9c-dd0ec3707698","order_by":7,"name":"Ni Zhou","email":"","orcid":"","institution":"Affiliated Taizhou Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Ni","middleName":"","lastName":"Zhou","suffix":""},{"id":392958474,"identity":"fedcdf2b-a8a3-4837-bc60-063cbcc0b22d","order_by":8,"name":"Yan Chen","email":"","orcid":"","institution":"Affiliated Taizhou Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Chen","suffix":""},{"id":392958475,"identity":"6ba97bdc-d713-416b-b6f9-b1fda295c011","order_by":9,"name":"Yonghui Lu","email":"","orcid":"","institution":"Affiliated Taizhou Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yonghui","middleName":"","lastName":"Lu","suffix":""},{"id":392958476,"identity":"cbbc8549-8615-4555-b818-f1c4ad08b62b","order_by":10,"name":"Yongzhi Tang","email":"","orcid":"","institution":"Affiliated Taizhou Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yongzhi","middleName":"","lastName":"Tang","suffix":""},{"id":392958477,"identity":"bd8a2b70-d066-4117-9b26-a53b201e1a3a","order_by":11,"name":"Hui Shao","email":"","orcid":"","institution":"Affiliated Taizhou Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Shao","suffix":""}],"badges":[],"createdAt":"2024-12-06 14:23:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5594401/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5594401/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72170513,"identity":"0aea828b-2945-4225-b90d-c58b4b98a5ac","added_by":"auto","created_at":"2024-12-23 11:00:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1065753,"visible":true,"origin":"","legend":"\u003cp\u003eAS prevalence rates and ND of prevalence for CLD among WCBA in 204 countries and regions in 2021. (A) AS prevalence rates of CLD among WCBA in 2021 worldwide. (B) NDs of CLD prevalence among WCBA from 1992 to 2021 worldwide.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-5594401/v1/3ff84cf65b59e66db41ce247.png"},{"id":72170517,"identity":"4540665b-1785-4244-a748-e8684e05f52e","added_by":"auto","created_at":"2024-12-23 11:00:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":385438,"visible":true,"origin":"","legend":"\u003cp\u003eLocal drifts and temporal changes in age distribution of CLD prevalence among WCBA from 1992 to 2021 across SDIRs quintiles. (A) Local drifts in CLD prevalence among WCBA across seven age groups. (B) Temporal changes in the age distribution of CLD prevalence among WCBA from 1992 to 2021.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-5594401/v1/e903f236d4b152c27c7a8525.png"},{"id":72171000,"identity":"c9dab1ac-0199-4cb3-bca8-d24da615c9a7","added_by":"auto","created_at":"2024-12-23 11:08:11","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":97715,"visible":true,"origin":"","legend":"\u003cp\u003eComposition of HBV, HCV, ALD, NAFLD, and other CLD among WCBA in different SDIRs from 1992 to 2021.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-5594401/v1/3b7c775d761d00670f8a77c5.png"},{"id":72170520,"identity":"326d059f-a8fa-4abf-85e7-0b6dbd07ba0f","added_by":"auto","created_at":"2024-12-23 11:00:11","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":437120,"visible":true,"origin":"","legend":"\u003cp\u003eEffects of age, period, and birth cohort on CLD prevalence among WCBA across SDI quintiles. (A) Age Effects; (B) Period Effects; (C) Birth Cohort Effects.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-5594401/v1/ad7d5abdbc2346c3fea875ed.png"},{"id":72170528,"identity":"fc09d22e-3b99-45a5-9c84-f6491aa1987b","added_by":"auto","created_at":"2024-12-23 11:00:11","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":784726,"visible":true,"origin":"","legend":"\u003cp\u003eThe effects of age, period, and birth cohort on prevalence of CLD among WCBA in the typical countries.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-5594401/v1/cceb84a9ada4703b9a7cdb47.png"},{"id":72172144,"identity":"68ad2bb1-b13e-4a54-a4d8-e1e86163bf1d","added_by":"auto","created_at":"2024-12-23 11:16:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3168274,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5594401/v1/da764c80-91a0-4584-b01e-8bea67a90ef9.pdf"},{"id":72170518,"identity":"4b8107c0-fdbf-486a-a60b-6f07908c58c4","added_by":"auto","created_at":"2024-12-23 11:00:11","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":758530,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfiles.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5594401/v1/9e512f3f0e87a3e22a7db73b.pdf"},{"id":72170515,"identity":"4c1df6e7-cd7f-44c1-860d-45adf358fc81","added_by":"auto","created_at":"2024-12-23 11:00:11","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":19960,"visible":true,"origin":"","legend":"","description":"","filename":"Table1GlobalandregionalprevalenceratesofCLDamongWCBA.docx","url":"https://assets-eu.researchsquare.com/files/rs-5594401/v1/2d4f9e889a9111cd1e93450a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Temporal Trends in Prevalence of Chronic Liver Disease among Women of Childbearing Age from 1992 to 2021","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCirrhosis and chronic liver disease (hereafter referred to as CLD) can arise from various etiologies, primarily including hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, excessive alcohol consumption, and non-alcoholic fatty liver disease (NAFLD) \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. CLD ranks among the top ten causes of global mortality \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Despite the decline in HBV incidence following vaccination programs \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e, the incidence of NAFLD and alcoholic liver disease (ALD) is on the rise, with the overall prevalence of CLD expected to escalate in the foreseeable future \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe World Health Organization (WHO) characterizes WCBA as women aged 15\u0026ndash;49 years, a demographic that constitutes approximately one-quarter of the global population. With a global fertility rate of 2.4 children per woman, the health status of women within this age group is closely tied to the well-being of newborns \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. As the incidence of liver disease continues to rise among WCBA, a concomitant increase in pregnancies in this demographic is noteworthy. Research indicates that the delivery rate among women with cirrhosis has nearly doubled over two decades \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. CLD significantly and adversely affects maternal morbidity and mortality \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Women with CLD are more likely to give birth to infants with low birth weight or preterm birth. Up to two-thirds of pregnant women with CLD may experience preterm birth, with deliveries before 30 weeks occurring in one-fifth of such pregnancies \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Pregnant women diagnosed with NAFLD face an elevated risk of developing gestational diabetes and preeclampsia \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWhile there are numerous studies on the prevalence of CLD in specific age groups, there is a lack of information on the trends of CLD prevalence among WCBA and particularly in relation to age, period, and birth cohort effects. The study extracted data on CLD among WCBA from GBD 2021 and utilized an APC model to analyze the temporal trends in CLD prevalence from 1992 to 2021 globally, regionally, and nationally.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eData Source\u003c/h2\u003e \u003cp\u003eThe GBD 2021 study, released in 2024, includes health and disease data from 1980 to 2021. It provides epidemiological assessments of 371 diseases and injuries across 204 countries and regions, with continuous data updates \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Extensive information on data inputs, processing methodologies, synthesis procedures, and final models are accessible in the associated GBD 2021 publications \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. The GBD network employed standardized Bayesian tools to integrate a vast array of data spanning time periods, age groups, geographical locations, and health conditions, enabling precisely estimation of disease burden. This methodology allows to estimate in countries lacking primary data sources by \"borrowing\" information from existing data, enabling comprehensive estimates of chronic disease burden globally.\u003c/p\u003e \u003cp\u003eThe SDI, derived from overall fertility rates for women under 25 years, average years of education for women aged 15 and above, and per capita income, is used to measure a country's or region's development level. Each country was categorized into five SDI quintiles based on the 2021 SDI value: low, low-middle, middle, high-middle, and high. We extracted the prevalence of CLD among WCBA in 204 countries and regions, categorized by SDI. All rates were per 100,000 population. The 95% uncertainty intervals (UIs) were defined using the 25th and 975th values of 1,000 ordered posterior distributions based on GBD algorithms \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAnalysis of Temporal Trends in CLD Prevalence among WCBA\u003c/h3\u003e\n\u003cp\u003eWe examined temporal trends in CLD prevalence among WCBA from 1992 to 2021, utilizing case numbers and age-standardized (AS) rates. AS prevalence rates were derived through direct age standardization, assuming rates follow the weighted sum of independent Poisson random variables. The relative distribution of CLD prevalence was figured out across seven distinct age group (45\u0026ndash;49, 40\u0026ndash;44, 35\u0026ndash;39, 30\u0026ndash;34, 25\u0026ndash;29, 20\u0026ndash;24, and 15\u0026ndash;19 years) among WCBA and the changes in prevalence age distribution over time were analyzed.\u003c/p\u003e \u003cp\u003eThe APC model is commonly employed to investigate the distinct contributions of age, period, and cohort effects on the prevalence and mortality of chronic diseases \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. In this study, the APC model was employed to examine temporal trends in prevalence, stratified by age, period, and birth cohort \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Given the complete linear relationship among age, period, and cohort, model identifiability becomes problematic. To resolve this issue, we derived estimable APC parameters and functions while avoiding arbitrary constraints in the model \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Detailed methodologies of the APC model have been discussed elsewhere \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. In this investigation, estimates of CLD prevalence among WCBA and corresponding population data from the GBD 2021 dataset were utilized as foundational inputs into the APC model.\u003c/p\u003e \u003cp\u003eIn our analysis, focusing on WCBA (15\u0026ndash;49 years), we employed seven distinct age groups (45\u0026ndash;49, 40\u0026ndash;44, 35\u0026ndash;39, 30\u0026ndash;34, 25\u0026ndash;29, 20\u0026ndash;24, and 15\u0026ndash;19 years). This age segmentation ensures alignment with the requisite five-year age intervals corresponding to five-year calendar periods, a fundamental requirement for the APC model. By adhering to these specifications, we aimed to capture comprehensive insights into how CLD prevalence evolves across different stages of reproductive age, thereby illuminating potential avenues for targeted intervention and policy formulation. Correspondingly, the study period (1992\u0026ndash;2021) was divided into six five-year periods: 1992\u0026ndash;1996, 1997\u0026ndash;2001, 2002\u0026ndash;2006, 2007\u0026ndash;2011, 2012\u0026ndash;2016, and 2017\u0026ndash;2021. Thus, 12 partially overlapping 10-year birth cohorts were used: 1942\u0026ndash;1951, 1947\u0026ndash;1956, 1952\u0026ndash;1961, 1957\u0026ndash;1966, 1962\u0026ndash;1971, 1967\u0026ndash;1976, 1972\u0026ndash;1981, 1977\u0026ndash;1986, 1982\u0026ndash;1991, 1987\u0026ndash;1996, 1992\u0026ndash;2001, and 1997\u0026ndash;2006.\u003c/p\u003e \u003cp\u003eThe APC model also estimates the overall annual percentage change in prevalence (ND, % per year) and he annual percentage change in prevalence within specific age groups (local drift, % per year). This reflects trends influenced by birth cohort effects \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. The significance of these annual percentage changes was figured out through Wald χ\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e test \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. In the APC model, the age effects were represented by fitted longitudinal age-specific rates adjusted for period deviations. The period and cohort influences were elucidated by the computation of period/cohort relative risks, which formulated as the ratios of prevalence rates associated with specific ages across each period/cohort relative to an arbitrarily selected reference period/cohort. It is noteworthy that the utilization of this reference period/cohort was inherently arbitrary and exerted no influence on the analytical robustness of the outcomes. It was attempted to process and visualize data through R 4.3.1 software. P-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicated statistical significance.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003eTrends in CLD prevalence in WCBA, 1992\u0026ndash;2021\u003c/h2\u003e\n \u003cp\u003eThe global and regional prevalence rates of CLD, AS prevalence rates, and NDs were shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. From 1992 to 2021, the global prevalence of CLD among WCBA surged by 53.42%, resulting in 413.67 million cases (95% UI: 377.66-459.28) in 2021, a reflection of the growing global population. The percentage variation in CLD prevalence was elevated across all SDIRs. In 2021, the global age-standardized prevalence rate of CLD among WCBA was 20,877.84 per 100,000 (95% UI: 17,250.33-25,044.54), an increase of 4.4% from 1992. Relative increases in age-standardized prevalence rate were observed in low-middle, high-middle, and high SDIRs. The APC model further estimated a global ND in CLD prevalence among WCBA at 0.057% per year (95% CI: 0.029%-0.084%), varying from \u0026minus;\u0026thinsp;0.27% (95% CI: -0.32% to -0.23%) in middle SDIR to 0.66% (95% CI: 0.62%-0.70%) in high SDIR.\u003c/p\u003e\n \u003cp\u003eNational prevalence rates and age-standardized prevalence rates of CLD among WCBA in 2021 and NDs of prevalence trends from 1992 to 2021 were demonstrated in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e and online supplemental table \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e. In 2021, 66 countries and regions had a CLD prevalence of at least 1 million, with China, India, Indonesia, Nigeria, and Brazil accounting for 47.35% of the global CLD prevalence among WCBA. In 103 countries, age-standardized prevalence rates reached at least the global average, with 21 countries, including Egypt, Qatar, and Kuwait, exceeding 1.5 times the global average prevalence, most of which were high and high-middle SDI countries. From 1992 to 2021, the United Arab Emirates had the highest increase in age-standardized prevalence (25.91%), with an annual ND of 0.92% (95% CI: 0.89%-0.94%). Age-standardized prevalence rates have declined in 90 countries. Although China and India had the highest CLD prevalence due to their large populations, their age-standardized prevalence rates decreased, with relatively minor changes in ND. Among the 204 countries and regions, the APC model estimated ND trends indicating an upward trend in 99 countries and regions, a downward trend in 86 countries, and a relatively stable trend in 19 countries, demonstrating strong heterogeneity in CLD prevalence trends globally.\u003c/p\u003e\n \u003cp\u003eThe annual percentage change in age-specific prevalence of CLD among WCBA, calculated by the APC model as local drifts was presented in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA and online supplemental table S2. Globally, the prevalence of CLD among WCBA declined in the 15\u0026ndash;19 and 20\u0026ndash;24 age groups but increased from the 30\u0026ndash;34 to 45\u0026ndash;49 age groups. The decline in the 15\u0026ndash;19 and 20\u0026ndash;24 age groups diminished with age. The prevalence of CLD in adolescents (15\u0026ndash;19 years) showed a declining trend across all SDIRs, with the steepest decline in high-middle SDIR (-1.66%, 95% CI: -1.41% to -1.91%) and the smallest decline in high SDIR (-0.24%, 95% CI: -0.11% to -0.36%). Moreover, in high SDIR, prevalence increased in all age groups except 15\u0026ndash;19 years. The local drifts in CLD prevalence for each age group across different countries were shown in online supplemental table S3.\u003c/p\u003e\n \u003cp\u003eThe temporal changes in age distribution of CLD prevalence among WCBA were shown in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB. Globally, CLD prevalence transitioned from 15\u0026ndash;19 years to 20\u0026ndash;49 years, a trend evident across all SDIR except low SDI. Additionally, older age groups represented a larger share of the prevalence, with over 50% of CLD prevalence in 2021 concentrated among women aged 35 years and older in all regions except low and low-middle SDIRs.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eComposition of CLD Causes among WCBA from 1992 to 2021 across Different SDI Regions\u003c/h3\u003e\n\u003cp\u003eIn all five SDIRs, NAFLD consistently constituted the largest proportion of CLD, accounting for over 50% of all liver diseases (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Globally, the prevalence of HBV declined, whereas NAFLD significantly increased, rising from 61.11% in 1992 to 74.24% in 2021, while HBV decreased from 27.34\u0026ndash;17.26%. This trend was consistent across all SDIR. HCV showed a slow decline globally and across SDIR, but in low SDIR, the decrease in HBV and increase in NAFLD were relatively moderate (HBV from 32.63% in 1992 to 29.81% in 2021, and NAFLD from 50.60% in 1992 to 59.19% in 2021). The proportion of ALD cases showed relatively minor changes, decreasing from 0.057% in 1992 to 0.052% in 2021 (online supplemental table S4).\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eAge, period and birth cohort effects on CLD prevalence in WCBA\u003c/h2\u003e\n \u003cp\u003eAge, period, and birth cohort effects derived from the APC model were shown in Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and online supplemental tables S5-S7. Age effects demonstrated uniform patterns across diverse SDIRs, exhibiting a minimal risk in the 15-19-year group that progressively elevated with advancing age. Specifically, high SDIRs consistently reported lower overall prevalence rates among all age-based groups relative to their lower SDI counterparts. Period effects revealed a remarkable trend: the prevalence initially attenuated before rising across most SDIRs, with notable exceptions in high and low SDIRs. During the study period, all regions except high and low SDIRs had more adverse period risks in most periods. In high SDIR, the risk increased gradually over time, while in low SDIR, the risk decreased gradually in later periods and stabilized thereafter. When comparing the 2017\u0026ndash;2021 period to the reference period of 2007\u0026ndash;2011, the relative period risk was 1.098 (95% CI: 1.086\u0026ndash;1.110) in high SDIRs, 1.054 (95% CI: 1.034\u0026ndash;1.075) in high-middle SDIRs, 1.036 (95% CI: 1.022\u0026ndash;1.050) in middle SDIRs, and 0.997 (95% CI: 0.993-1.000) in low SDIRs. Regarding birth cohort effects, the prevalence risk for successive birth cohorts globally initially increased and then decreased, with overall improvements in prevalence across all SDIRs for successive birth cohorts. Relative to individuals born in the 1982\u0026ndash;1991 cohort, the relative cohort risk for those form the 1997\u0026ndash;2006 cohort was 0.836 (95% CI: 0.828\u0026ndash;0.844) in low-middle SDIR and 0.908 (95% CI: 0.872\u0026ndash;0.945) in high SDIR.\u003c/p\u003e\n \u003cp\u003eThe influence of age, period, and birth cohort on CLD prevalence among WCBA in each country was presented in online supplemental tables S8-S10. The temporal trends in global CLD prevalence, highlighting several typical countries with relatively favorable and unfavorable age, period, and birth cohort effects across different SDI quintiles were illustrated in Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e. The United States, a high SDI country, demonstrated unfavorable trends, with no observed decline in prevalence across all age groups in recent years, and worsening period and cohort risks. In contrast, Australia showed more favorable trends in cohort risks among high SDI countries. China and Spain serve as examples of high-middle SDI countries, demonstrating a transition in prevalence from adolescence to adulthood. In both China and Spain, the prevalence rates among the elderly population were rising. China showed an early decline in risk followed by an increase in later stages, while Spain exhibited a sustained increase, and the birth cohort risks in both countries tended to decrease in later stages. Among low SDI countries, Sierra Leone and the Central African Republic showed declining prevalence across all age groups, with period risks initially decreasing then increasing, and gradually decreasing cohort risks.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eGlobally, CLD stands as a profound determinant of morbidity and mortality, and 2\u0026nbsp;million deaths are attributed to liver disease annually \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. CLD can lead to severe complications and death, significantly impacting quality of life and imposing a substantial economic burden \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Despite various conditions leading to CLD, HBV, HCV, NAFLD, and ALD are the most common culprits \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn 2015, the United Nations established defined objectives under Sustainable Development Goal 3, with a target to decrease the global maternal mortality ratio to less than 70 per 100,000 live births by 2030 \u003csup\u003e18\u003c/sup\u003e. In comparison to the broader obstetric population, expectant mothers with CLD confront elevated risks of adverse outcomes affecting both maternal health and fetal well-being. These include gestational hypertension, gestational diabetes, preeclampsia, preterm birth, and low birth weight \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Such severe complications not only pose significant challenges to maternal survival but also impede progress towards achieving the United Nations' Sustainable Development Goals. This study explored the relative influence of age, period, and birth cohort on the prevalence trends of CLD among WCBA.\u003c/p\u003e \u003cp\u003eAge effects demonstrated consistent patterns across various SDIRs, with risks escalating with advancing age. This is understandable, as CLD develops over time due to continuous damage to liver cells, and prolonged exposure to risk factors with age ultimately leads to CLD \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Globally, we observed adverse period effects and favorable birth cohort effects. CLD period effects have been rising over the past decade. Period effects reflect changes in incidence or mortality rates due to societal, economic, cultural, or environmental changes \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Over time, with improvements in socio-economic conditions, education, and living standards, the overall incidence of CLD has increased. Recent studies indicated that the rising prevalence of CLD is mainly driven by the increasing prevalence of NAFLD \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. The global prevalence of obesity and type 2 diabetes is a major contributor to the rising prevalence and progression of NAFLD \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Factors such as increased calorie intake, dietary changes, reduced physical activity levels, and alterations in gut microbiota contribute to this trend \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Air pollution has also recently been identified as a potential risk factor for liver disease \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Future health education on NAFLD and the promotion of healthy lifestyles and dietary habits for individuals over 30 years old are recommended \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt is encouraging to note that the prevalence of HBV is declining. With improved access to HBV vaccines globally, implementation of mother-to-child transmission prevention programs, and approval of antiviral medications for children and adolescents, the incidence of chronic viral hepatitis has significantly reduced \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. This is consistent with our findings, although the decline was slower in low SDIR. In low SDIR, limited access to antiviral medications \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e, challenges in standardizing screening and diagnosis, and low HBV vaccine coverage exacerbate the prevention and treatment burden of liver diseases among WCBA \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. As of 2016, nearly half of children aged 1 to 6 in India had not been administered the hepatitis B vaccine \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Expanding screening for HBV, increasing vaccine coverage, and improving access to antiviral drugs are crucial in these regions.\u003c/p\u003e \u003cp\u003eRegarding birth cohort effects, individuals born after 1980\u0026ndash;1989 generally exhibited lower risks than those born earlier, consistent with the introduction and widespread use of HBV vaccines. In the 1980s and 1990s, many countries adopted this vaccine \u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. The WHO recommends routine HBV immunization for newborns globally and has been promoting the inclusion of HBV vaccines in national immunization programs since 1992. Surveys indicated that between 1990 and 2019, the prevalence of HBV surface antigen among infants and children aging under five years old declined by 77% \u003csup\u003e3\u003c/sup\u003e. Additionally, with social progress, significant improvements in healthcare services for newborns have been observed.\u003c/p\u003e \u003cp\u003eFirstly, it describes the prevalence trends of CLD among WCBA, but significant socio-economic and clinical changes worldwide over the past three decades may have altered the impact of each type of CLD, which this article does not detail. Secondly, in some underdeveloped countries with lower healthcare standards, misdiagnosis and underdiagnosis of diseases may lead to underestimation. The GBD collaborators use extensive statistical modeling methods, which may affect the accuracy of age, period, and birth cohort effect estimates. Thirdly, the lagging nature of GBD data should be noted. In summary, nearly half of the countries worldwide were experiencing an upward trend in CLD. Concurrently, worsening risks in many countries indicated a significant shortfall in resources allocated to WCBA CLD healthcare. It is noteworthy that while HBV is declining, NAFLD is rapidly increasing.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ealcoholic liver disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAPC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eage-period-cohort\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eage-standardized\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econfidence interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCLD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003echronic liver disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGBD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlobal Burden of Disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHBV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehepatitis B virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHCV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehepatitis C virus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNAFLD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enon-alcoholic fatty liver disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eND\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003enet drift\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSDI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esociodemographic index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003euncertainty interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWCBA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ewomen of childbearing age\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Health Organization.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eThis investigation was made possible through the financial backing provided by the Key Research and Development Project of Zhejiang Province (2023C03046) and further bolstered by the Taizhou Science and Technology Program (1901ky14).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContributors\u0026nbsp;\u003c/strong\u003eH.D.C and H.W.W were instrumental in conceptualizing and designing the study, as well as in acquiring the raw data, conducting the analysis, and preparing the visual representations. The initial drafting of the manuscript was undertaken by H.D.C. H.W.W, A.L.L, and J.Y.L provided in-depth critical review and revisions. \u0026nbsp;Y.H.L, L.L, N.Z, and Y.C contributed to data collection, analysis, and visualization. Y.Z.T, H.S, and W.T.W oversaw the final manuscript preparation. All authors, who engaged in this investigation, granted their approval of the final manuscript, and endorsed its submission. H.S assumes ultimate responsibility as the guarantor for the overall integrity of the content.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e The authors affirmed the absence of competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003eThe University of Washington\u0026rsquo;s Institutional Review Board has authorized a waiver of informed consent for the utilization of deidentified data in the GBD study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e Data of the study are accessible via the Institute for Health Metrics and Evaluation (IHME)\u0026rsquo;s online platform, found at https://vizhub.healthdata.org/gbd-results/.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKulik, L. \u0026amp; El-Serag, H. B. 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Progress towards hepatitis B prevention through vaccination in the Western Pacific, 1990-2014. \u003cem\u003eVaccine\u003c/em\u003e \u003cstrong\u003e34\u003c/strong\u003e, 2855-2862, doi:10.1016/j.vaccine.2016.03.060 (2016).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Age-period-cohort model, Chronic liver disease, Global Burden of Disease, Sociodemographic index, Temporal trend, Women of childbearing age","lastPublishedDoi":"10.21203/rs.3.rs-5594401/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5594401/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChronic liver disease (CLD) is among the foremost contributors to global mortality. This investigation attempted to profoundly analyze temporal trends in CLD prevalence among women of childbearing age (WCBA) over a span of 30 years.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAn age-period-cohort (APC) model was constructed to determine the overall annual percentage change (net drift [ND], % per year) and annual percentage change within discrete age brackets (local drift, % per year) in CLD prevalence from 1992 to 2021. The APC model accommodates longitudinal age-specific rates while adjusting for deviations across periods from 1992 to 2021 (age effects), as well as period/cohort relative risks (period/cohort effects).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFrom 1992 to 2021, the global ND in CLD prevalence among WCBA was 0.057% per year (95% confidence interval [CI]: 0.029%-0.084%), varying across regions (from \u0026minus;\u0026thinsp;0.27\u0026ndash;0.66%). From the local drift perspective, age groups with increasing prevalence were more prevalent in high SDI region (SDIR), while those with decreasing were more common in low SDIR. Age effects showed a consistent patterns across different SDIRs, with an incremental rise in risk associated with advancing age. Period risks were relatively lower in low SDIR, while other regions demonstrated more adverse period risks. Furthermore, across birth cohorts, improvements in prevalence were observed in all regions.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eOver the past 30 years, the global prevalence of CLD among WCBA has demonstrated a predominantly adverse trend. Strategic advancements in prevention, management, and treatment of CLD could mitigate relative risks for successive birth cohorts.\u003c/p\u003e","manuscriptTitle":"Temporal Trends in Prevalence of Chronic Liver Disease among Women of Childbearing Age from 1992 to 2021","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-23 11:00:06","doi":"10.21203/rs.3.rs-5594401/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-03-04T05:53:19+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-02-26T03:26:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"135301097020404594459148026860378153611","date":"2025-02-26T01:32:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-02-24T08:28:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-02-17T18:15:58+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-12-20T16:54:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-12-19T12:43:41+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-12-06T14:21:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2391a6e6-8581-4943-9931-511b44eb355a","owner":[],"postedDate":"December 23rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":41896203,"name":"Health sciences/Gastroenterology/Hepatology"},{"id":41896204,"name":"Health sciences/Medical research/Epidemiology"}],"tags":[],"updatedAt":"2025-05-06T08:23:47+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-23 11:00:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5594401","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5594401","identity":"rs-5594401","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}