Geographical Variations in Mortality Rates From Chronic Liver Disease and Cirrhosis in the US in Younger Adults: A Time-Trend Analysis Using the CDCs National Center of Health Statistics Database, 2000-2020

Introduction: Previous data showed increasing mortality from chronic liver disease and cirrhosis (CLDC) in younger adults in the US. However, there are limited data on geographical variations of sex-specific CLDC-related mortality trends. The aim of this study was to conduct a time-trend analysis of CLDC mortality rates in younger adults using a nationwide US database, the CDC’s NCHS database. Methods: Data were collected from the NCHS database, which is the most comprehensive source of mortality statistics in the US, covering 100% of the US population. CLDC mortality rates in younger adults (aged < 55 years) were age-adjusted to the standard 2000 US population using SEER*Stat software and were categorized by sex and US state. Time-trends, reported as annual percentage change (APC) and average APC (AAPC), were calculated using Joinpoint Regression Software utilizing Monte Carlo permutation analysis to estimate the best-fit trend. Sex-specific pairwise comparison was conducted using the tests of parallelism and coincidence, and the absolute AAPC difference was evaluated using parametric estimations (2-sided P-value cut-off at 0.05). Results: CLDC mortality rates in younger men (165,619 deaths) varied based on state and were either increasing, stable, or decreasing. On the other hand, in younger women (80,530 deaths), CDLC mortality rates were increasing in most states and stable in a few. A greater increase in CLDC mortality rates in younger women compared to counterpart men with non-parallel data was seen in Alabama, Arizona, Arkansas, Colorado, Florida, Louisiana, Maryland, Massachusetts, Missouri, Ohio, Oklahoma, Pennsylvania, South Carolina, Virginia, Washington, and West Virginia (P-values< 0.05) (Table 1). The biggest AAPC-difference in sex-specific trends was seen in West Virginia (AAPC-difference=4.08, P< 0.001) and Pennsylvania (AAPC-difference=3.84, P< 0.001). Conclusion: Our nationwide analysis of nearly 100% of deaths attributed to CLDC in younger adults showed that West Virginia and Pennsylvania, which are part of UNOS Region 2, were the states with the biggest disparities in CLDC outcomes between younger women and men. Previous data showed that UNOS Region 2 had shortage in living donors, longer waitlist for liver transplantation, and accounted for significant number of annual deaths on liver transplant waitlist. Future studies are warranted to further investigate the disparities in younger adults with the goal to improve outcomes in all US states. Table 1. - Sex-Specific Trends for Chronic Liver Disease and Cirrhosis (CLDC) Mortality in Younger Adults Categorized by US State US State Deaths (N=716,651)a Trendsb Sex-specific AAPC differencec (95% CI) Pairwise comparison P-values Time period APC (95% CI) AAPC (95% CI) Sex-specific AAPC difference Coincidenced Parallelisme Alabama Women 1,368 (0.19%) 2000-2010 0.04 (-3.46 to 3.67) 3.80 (1.62 to 6.03) -2.73 (-5.11 to -0.36) 0.02 < 0.001 < 0.001 2010-2020 7.70 (4.61 to 10.88) Men 2,619 (0.36%) 2000-2013 -0.67 (-1.54 to 0.21) 1.07 (0.19 to 1.96) 2013-2020 4.38 (2.15 to 6.65) Arizona Women 2,685 (0.37%) 2000-2020 3.21 (2.41 to 4.02) 3.21 (2.41 to 4.02) -3.51 (-4.74 to -2.27) < 0.001 < 0.001 < 0.001 Men 4,700 (0.65%) 2000-2008 -3.50 (-5.49 to -1.46) -0.30 (-1.26 to 0.68) 2008-2020 1.90 (0.80 to 3.01) Arkansas Women 739 (0.10%) 2000-2020 4.26 (2.56 to 5.99) 4.26 (2.60 to 6.00) -2.22 (-4.12 to -0.33) 0.02 < 0.001 0.008 Men 1,436 (0.20%) 2000-2020 2.04 (0.97 to 3.12) 2.03 (0.97 to 3.12) Colorado Women 2,071 (0.28%) 2000-2020 4.62 (3.69 to 5.55) 4.61 (3.70 to 5.54) -2.06 (-3.22 to -0.88) 0.001 < 0.001 0.03 Men 3,635 (0.51%) 2000-2020 2.56 (1.74 to 3.40) 2.56 (1.73 to 3.40) Florida Women 5,831 (0.81%) 2000-2020 1.26 (0.71 to 1.82) 1.26 (0.70 to 1.81) -2.45 (-3.48 to -1.42) < 0.001 < 0.001 < 0.001 Men 11,084 (1.54% 2000-2011 -2.74 (-3.89 to -1.59) -1.19 (-2.07 to -0.29) 2011-2020 -0.74 (-0.87 to 2.38) 2017-2020 7.31 (5.48 to 9.18) Louisiana Women 1,016 (0.14%) 2000-2020 2.95 (1.55 to 4.37) 2.95 (1.55 to 4.36) -3.15 (-4.62 to -1.68) < 0.001 < 0.001 < 0.001 Men 2,148 (0.30%) 2000-2020 -0.19 (-0.89 to 0.50) -0.195 (-0.88 to 0.50) Maryland Women 1,086 (0.15%) 2000-2017 -1.52 (-2.79 to -0.24) 2.09 (-0.45 to 4.68) -3.40 (-6.47 to -2.16) 0.03 < 0.001 0.008 2017-2020 25.19 (6.08 to 47.75) Men 2,140 (0.29%) 2000-2014 -4.56 (-5.87 to -3.23) -1.31 (-2.99 to 0.40) 2014-2020 6.72 (1.23 to 12.51) Massachusetts Women 1,392 (0.19%) 2000-2015 0.73 (-0.62 to 2.11) 3.86 (2.16 to 5.58) -3.60 (-5.60 to -1.59) < 0.001 < 0.001 < 0.001 2015-2020 13.84 (7.37 to 20.69) Men 2,853 (0.40%) 2000-2020 0.27 (-0.84 to 1.39) 0.266 (-0.84 to 1.38) Missouri Women 1,246 (0.17%) 2000-2015 2.59 (0.90 to 4.32) 4.69 (2.64 to 6.77) -3.43 (-5.73 to -1.12) 0.004 < 0.001 0.03 2015-2020 11.24 (3.79 to 19.22) Men 2,634 (0.36%) 2000-2020 1.26 (0.17 to 2.36) 1.26 (0.17 to 2.38) Ohio Women 2,835 (0.39%) 2000-2008 0.87 (-2.01 to 3.82) 3.40 (2.07 to 4.76) -2.59 (-4.02 to -1.16) < 0.001 < 0.001 < 0.001 2008-2020 5.14 (3.74 to 6.55) Men 5,834 (0.81%) 2000-2020 0.82 (0.30 to 1.34) 0.82 (0.30 to 1.34) Oklahoma Women 1,452(0.20%) 2000-2020 3.92 (2.91 to 4.94) 3.92 (2.91 to 4.94) -3.72 (-0.96 to -3.31) 0.001 < 0.001 0.003 Men 2,695 (0.37% 2000-2020 1.59 (0.51 to 2.67) 1.59 (0.51 to 2.67) Pennsylvania Women 2,385 (0.33%) 2000-2020 2.82 (2.05 to 3.60) 2.81 (2.04 to 3.59) -3.84 (-4.86 to -2.82) < 0.001 < 0.001 < 0.001 Men 5,099 (0.71%) 2000-2020 -1.02 (-1.78 to -0.26) -1.02 (-1.77 to -0.25) South Carolina Women 1,379 (0.19%) 2000-2020 3.01 (1.84 to 4.19) 3.00 (1.84 to 4.19) -2.87 (-4.18 to -1.55) < 0.001 < 0.001 < 0.001 Men 2,763 (0.38%) 2000-2020 0.14 (-0.63 to 0.92) 0.14 (-0.62 to 0.91) Virginia Women 1,608 (0.22%) 2000-2020 3.44 (2.46 to 4.43) 3.44 (2.46 to 4.42) -3.38 (-4.58 to -2.18) < 0.001 < 0.001 < 0.001 Men 3,391 (0.47%) 2000-2020 0.06 (-0.76 to 0.88) 0.05 (-0.76 to 0.88) Washington Women 2,231 (0.31%) 2000-2020 3.88 (2.88 to 4.88) 3.877 (2.88 to 4.88) -1.45 (-2.67 to -0.23) 0.02 < 0.001 0.01 Men 3,784 (0.52%) 2000-2020 2.42 (1.60 to 3.26) 2.42 (1.60 to 3.26) West Virginia Women 485 (0.06%) 2000-2020 4.96 (3.32 to 6.63) 4.96 (3.32 to 6.62) -4.08 (-5.94 to -2.22) < 0.001 < 0.001 0.001 Men 1,313 (0.18%) 2000-2020 0.88 (-0.21 to 2.00) 0.88 (-0.21 to 1.99) aData are presented as death count numbers followed by percentages of the death count numbers from the total cases of deaths attributed to CLDC in the database.bTime-trends were computed using Joinpoint Regression Program (v4.9.0.1, NCI) with 3 maximum joinpoints allowed (4-line segments).cA negative value indicates a greater AAPC in women compared to men.dTests whether sex-specific trends were identical. A significant P-value indicates that the trends were not identical (i.e., they had different mortality rates and coincidence was rejected).eTests whether sex-specific trends were parallel. A significant P-value indicates that the trends were not parallel (i.e., parallelism was rejected). * Indicates that there were too few CLDC-related deaths per 1 calendar year at least hindering the calculation of a rate and thus a trend.