Trends and disparities in mortality from sideroblastic anemia and liver diseases in US adults (1999–2023): A CDC wonder analysis

Abstract Introduction: Sideroblastic anemia and liver diseases are clinically distinct but often interlinked through similar metabolic pathways such as alcohol toxicity, mitochondrial dysfunction, and altered iron metabolism. Chronic liver disease contributes to anemia through impaired haematopoiesis, while sideroblastic anemia exhibits ineffective erythropoiesis and iron overload. These overlapping mechanisms are rapidly emerging in clinical settings. However, mortality trends and demographic disparities involving these conditions in the United States remain underexplored. This study analyses national CDC WONDER mortality data from 1999 to 2023 to assess patterns across age, sex, race and ethnicity, region, and urbanization status. Methods: We conducted a retrospective analysis of the CDC WONDER mortality data using the publicly available death certificates from 1999 to 2023 for individuals aged ≥ 25 years. Sideroblastic anemia and liver diseases were identified using the International Classification of Disease, tenth revision (ICD-10) codes D64 and K70-K76, respectively. Death certificates were identified where sideroblastic anemia and liver diseases were listed as contributing causes of death. Age-adjusted mortality rates (AAMRs) were extracted per 100,000 of the population. Joinpoint regression was used to calculate Annual Percent Changes (APCs) in AAMRs and trends were analyzed by gender, race, regions, urbanization and states. Results: A total of 60,093 deaths were reported from 1999 to 2023 attributed to sideroblastic anemia and liver diseases in US adults. The overall AAMR increased from 0.75 in 1999 to 1.16 in 2018 (APC: 1.81; 95% CI: 1.53 to 2.09) and then increased again during the COVID-19 pandemic to 1.7 in 2021 (APC: 15.22; 95% CI: 7.81 to 23.13), before slightly decreasing to 1.61 in 2023 (APC: -1.17; 95% CI: -8.5 to 6.82). The AAMRs were higher in men (1.29) than in women (0.83). Individuals of Hispanic ancestry demonstrated the highest AAMR (1.69) throughout the study period, followed by Non-Hispanic (NH) Black (1.15), NH White (1.03), and NH Asians or Pacific Islanders (0.71). Non-metropolitan areas had slightly higher AAMRs than metropolitan areas (1.05 vs 0.93), while among the census regions, the West had the highest mortality burden (AAMR: 1.25) and the Northeast had the lowest mortality rates (AAMR: 0.8). Older adults aged 65 or above had the highest mortality rates among different age groups. Among the states, Texas, California, West Virginia, North Dakota, New Mexico, and South Carolina were among the top 90th percentile of deaths due to sideroblastic anemia and liver diseases. Conclusion: Over the past 24 years, mortality linked to coexisting sideroblastic anemia and liver diseases has increased in the U.S., with a pronounced increase in recent years. The burden remains highest among males, and non-Hispanic Whites, and residents of non-metropolitan areas underscoring persistent demographic disparities. The upward trend highlights the need for greater clinical awareness of their co-occurrence, particularly in populations facing barriers to early diagnosis and care. Expanding access to timely screening, particularly in individuals with alcohol consumption or metabolic dysfunction, may improve outcomes. Public health strategies must address shared risk factors and healthcare inequities to reduce future mortality rates from these concurrent conditions.