S2470 Silent Synergy: A 25-Year US Analysis of Sepsis-Related Mortality in Older Adults With Chronic Liver Disease

Introduction: Chronic liver disease (CLD) compromises immune surveillance, gut barrier integrity, and systemic inflammatory regulation, rendering patients highly susceptible to severe infections, particularly sepsis. Older adults with CLD face a disproportionately high risk due to age-related immunosenescence and frequent co-morbidities. Sepsis not only accelerates hepatic decompensation but also dramatically worsens outcomes, often leading to multi-organ failure and death. Despite the growing recognition of sepsis as a leading cause of hospitalization in CLD, national mortality trends in this vulnerable subgroup remain poorly characterized. This study analyzes long-term trends and disparities in CLD and sepsis-related deaths among U.S. adults aged 55+ from 1999 to 2023. Methods: We extracted mortality data from CDC WONDER (1999–2023) using International Classification of Diseases, Tenth Revision codes for CLD and sepsis. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated using the 2000 U.S. standard population. Joinpoint regression estimated Annual Percent Change (APC) and Average APC (AAPC), with P < 0.05 considered significant. Results: There were 137,129 deaths from CLD and sepsis among adults ≥55, with 82% occurring in inpatient settings. The AAMR more than doubled, rising from 4.12 (1999) to 9.88 (2023) (AAPC: 4.0%, 95% CI: 3.6–4.4, P < 0.000001). Men had nearly twice the mortality of women (8.3 vs 4.9), though women had a steeper increase (AAPC: 4.6% vs 4.2%). Adults aged 55–74 had higher AAMRs than those 75+, but older adults showed faster increases (AAPC: 4.5% vs 3.6%). Non-Hispanic American Indians had the highest AAMR (17.1) and steepest rise (AAPC: 4.7%, P < 0.00001). Regionally, the West had the highest AAMR (8.33) and fastest increase (AAPC: 4.4%). Kentucky reported the highest state-level AAMR (13.9), while Maine had the lowest (3.2). Urban areas had slightly higher mortality (6.5 vs 5.8), but rural areas saw faster growth (AAPC: 5.9% vs 3.6%). Conclusion: Mortality from CLD and sepsis in older adults has surged over 2 decades, with marked disparities by sex, age, race, and geography. Sharp increases among women, the elderly, NH American Indians, and rural populations highlight the need for tailored interventions. Elevated and rising rates in regions like the West and states like Kentucky reveal urgent care gaps. These findings underscore the importance of early recognition, integrated care models, and targeted public health strategies to reduce preventable deaths.