Trends in Sepsis-Related Mortality among Individuals with Liver Disease in the United States: 1999–2020

Background: Sepsis and liver disease represent significant and intersecting public health challenges, yet trends in sepsis-related mortality among individuals with liver disease remain poorly characterized. This study examines national mortality trends from 1999 to 2020, evaluating disparities by sex, race/ethnicity, and geographic location. Methods: Using CDC WONDER data, we analyzed age-adjusted mortality rates (AAMRs) for sepsis-related deaths among individuals with liver disease (ICD-10 codes K70-K76 and A40-A41). Joinpoint regression identified temporal trends, and annual percent change (APC) quantified rate variations. Analyses were stratified by sex, race/ethnicity, urbanization level, and census region. Results: Mortality rates showed a significant nationwide increase, particularly accelerating after 2009. Disparities emerged across demographic groups, with American Indian/Alaska Native populations experiencing the highest mortality rates overall, while Black/African American communities saw alarming late-period surges. Geographic patterns revealed particular challenges in rural areas and Midwestern states, where mortality rates climbed most steeply. Urban-rural divides widened over time, with non-metropolitan areas eventually surpassing urban mortality rates. Sex-based differences persisted, with males maintaining higher baseline mortality but females experiencing faster rate increases in recent years. These patterns suggest evolving epidemiological challenges that disproportionately affect certain populations and regions. The findings highlight the complex interplay between clinical, geographic, and socioeconomic factors influencing outcomes for this vulnerable patient population. Conclusions: Sepsis-related mortality among individuals with liver disease has risen markedly, with inequitable burdens across demographic and geographic subgroups. The findings underscore the need for targeted interventions addressing systemic disparities in healthcare access, social determinants, and clinical management.