S2440 Gender-Based Differences in Liver Disease Mortality Among Adults Aged 15-44 in the United States, 1999-2020

Introduction: Liver disease is a growing public health concern in the United States, especially for young adults. Emerging evidence also points to shifting epidemiologic patterns in women of reproductive age. However, gender-specific analyses in young adults remain limited. This study evaluates national gender trends in liver disease mortality among individuals aged 15-44 over 22 years. Methods: This was a cross-sectional retrospective study using the CDC WONDER database from 1999 to 2020. International Classification of Diseases, Tenth Revision (ICD-10) codes K70-K76 were used to analyze liver-related Age-Adjusted Mortality Rate (AAMR) per 100,000 individuals. Annual percent changes (APCs) with 95% confidence intervals were calculated using Joinpoint regression for both sexes. A test for parallelism (significance threshold of P < 0.05) was also conducted to evaluate whether man and woman trends differed significantly over time. Results: A total of 99,132 deaths (woman: 36,957; man: 62,175) from liver disease were reported in the U.S. from 1999 to 2020. Two joinpoints were identified for both genders, dividing the period into 3 distinct segments. Among women the AAMR declined slightly but not statistically significantly from 1999 to 2009 with an annual percent change (APC) of -1.03% (95% CI: -4.10 to 0.29, P = 0.097), followed by a significant increase of 3.87% per year from 2009 to 2018 (95% CI: 0.37 to 5.90, P = 0.0416), and a sharp rise of 18.23% annually from 2018 to 2020 (95% CI: 6.38 to 24.67, P < 0.0001). In men, mortality declined significantly between 1999 and 2006 (APC = -3.85%, 95% CI: -6.13 to -2.53, P < 0.0001), increased modestly from 2006 to 2018 (APC = 1.21%, 95% CI: 0.50 to 2.05, P = 0.0032), and then surged between 2018 and 2020 with an APC of 25.96% (95% CI: 18.10 to 30.72, P < 0.0001). The most pronounced increases in AAMR occurred after 2018, with the steepest rise in men. The Pairwise Comparison revealed a significant difference between man and woman trends (P = 0.000444) indicating that the observed mortality trajectories were not parallel across genders. Conclusion: Liver disease mortality has increased sharply among young adults in the U.S. particularly in recent years. The post-2018 acceleration was more pronounced in men (+25.96%) than women (+18.23%), however, both were statistically significant. These findings suggest an alarming escalation in mortality underscoring the need for interventions addressing possible causes that intensified including substance use, healthcare access and socioeconomic disparities.