Background and aimsPrevious studies show that mortality from chronic liver disease (CLD) and cirrhosis is increasing in the U.S. However, there are limited data on sex-specific mortality trends by age, race, and geographical location. The aim of this study was to conduct a comprehensive time-trend analysis of liver disease related mortality rates in the National-Center-of-Health-Statistics(NCHS) database. MethodsCLD and cirrhosis mortality rates between 2000-2020(age-adjusted to the 2000-standard-U.S.-population) were collected from the NCHS database and categorized by sex and age into older adults(≥55 years) and younger adults(<55 years), race (Non-Hispanic-White, Non-Hispanic-Black, Hispanic, Non-Hispanic-America- Indian/Alaska-Native, and Non-Hispanic-Asian/Pacific-Islander), U.S. state, and cirrhosis etiology. Time-trends, annual percentage change (APC) and average APC (AAPC), were estimated using Joinpoint Regression utilizing Monte Carlo permutation analysis. We used tests for parallelism and identicalness for sex-specific pairwise comparisons of mortality trends(two-sided P-value cut-off=0.05). ResultsBetween 2000-2020, there were 716,651 deaths attributed to CLD and cirrhosis in the U.S. (35.68% women). In the overall population and in older adults, CLD and cirrhosis-related mortality rates were increasing similarly in men and women. However, in younger adults (246,149 deaths, %32.72 women), the rate of increase was greater in women compared to men(AAPC=3.04 vs 1.08, AAPC-Difference=1.96,P<0.001), with non-identical non-parallel data(P-values<0.001). The disparity was driven by Non-Hispanic-White(AAPC=4.51 vs 1.79, AAPC-difference=2.71,P<0.001) and Hispanic(AAPC=1.89 vs -0.65,AAPC-difference=2.54,P=0.001) individuals. The disparity varied between U.S. states and was seen in 16 states, mostly in West Virginia(AAPC=4.96 vs 0.88, AAPC-difference=4.08,P<0.001) and Pennsylvania(AAPC=2.81 vs -1.02, AAPC-difference=3.84,P<0.001). Etiology-specific analysis did not show significant sex disparity in younger adults. ConclusionMortality rates due to CLD and cirrhosis in the U.S. are increasing disproportionately in younger women. This finding was driven by higher rates in Non-Hispanic White and Hispanic individuals, with variation between U.S. states. Future studies are warranted to identify the reasons for these trends with the ultimate goal of improving outcomes.
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