S2778 Trends and Disparities in Mortality From Acute Liver Failure: A CDC WONDER Database Analysis (1999–2023)

Introduction: Acute liver failure (ALF) is a life-threatening syndrome with diverse etiologies, including drug-induced injury (acetaminophen), viral hepatitis, and autoimmune hepatitis. Despite advances in critical care and transplantation, comprehensive analyses of ALF mortality trends and demographic disparities in the U.S. remain limited. Methods: Using the CDC WONDER Multiple Cause of Death database (1999–2023), we extracted ALF-related deaths via International Classification of Diseases, Tenth Revision (ICD-10) code K72.0. Age-adjusted mortality rates (AAMR per 100,000) were stratified by sex, race/ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic, Asian/Pacific Islander [API], American Indian/Alaska Native [AIAN]), age groups, and census regions. Temporal trends were analyzed using joinpoint regression to compute annual percentage changes (APC) and inflection points. Results: From 1999–2023, ALF, age-adjusted mortality rates (AAMR) demonstrated a biphasic trend: an initial decline (APC: −1.2% during 1999–2010) followed by a significant increase (APC: +3.8% from 2010–2023). Striking disparities emerged, with American Indian/Alaska Native (AIAN) populations exhibiting the highest AAMR (4.11 per 100,000) and a steep post-2013 mortality surge (APC: +14.58%). Non-Hispanic Black and Hispanic cohorts maintained persistently elevated rates relative to Non-Hispanic White individuals (rate ratio [RR]: 1.26 in 1999 to 1.15 in 2023), while Asian/Pacific Islander populations recorded the lowest AAMR (3.61). Adults aged 45–64 years experienced the sharpest mortality acceleration (APC: +5.6% during 2015–2023), surpassing rates in those ≥75 years (AAMR: 9.61). Gender and geographic disparities were prominent, with men demonstrating higher mortality than women (AAMR: 2.86 vs 1.41), and the South and West census regions reporting the highest burden (AAMR: 2.23 and 2.24, respectively). Rural areas showed accelerated mortality increases (APC: +2.64%). A pronounced mortality peak occurred in 2020–2021, coinciding with the COVID-19 pandemic and rising drug-induced liver injuries. Conclusion: Since 2010, ALF-related mortality has been on the rise with widening disparities among AIAN, middle-aged, and rural populations. The persistence of such inequities highlights the systemic gaps in prevention, early intervention and access to specialty care. Public health strategies must prioritize and target screening of high-risk subgroups and strengthen regional transplant referral networks.