25-Year Mortality Trends of Hepatorenal Syndrome Vs Portal Hypertension in Older U.S. Adults with Liver Diseases: A CDC WONDER and “ARIMA Based” Analysis

Introduction: As of 2019, liver cirrhosis has been ranked as the 11th leading cause of death in the U.S. Despite medical advances and available therapies, overall survival outcomes remain limited for hepatorenal syndrome (HRS) and portal hypertension (PH) have remain poor. This study seeks to evaluate the comparative disparities among liver disease patients with HRS or PH. Methodology: Mortality data from the CDC WONDER database (1999–2023) was retrieved for individuals aged ≥55 years with liver disease (ICD-10 K70–K76), focusing on HRS (K76.7) and PH (K76.6) as the contributing causes of death. Joinpoint regression analysis (JPR) was used to estimate Annual Percent Change (APC) with 95% confidence intervals (CI), stratified by age, sex, race/ethnicity, U.S. Census regions, and 2013 urbanization framework. Autoregressive Integrated Moving Average ARIMA: (0,2,1) approach was used to predict AAMRs up to 2035 along with their 95% confidence intervals. We applied Ljung-Box test to validate the model’s efficacy. A threshold for statistical significance was set at <0.05. Results: From 1999–2023, there were 14,104 PH-related deaths (AAMR: 0.69) and 47,139 HRS-related deaths (AAMR: 2.35). AAMRs for HRS group and PH group are projected to reach 3.58 (95% CI: 1.48-5.67; Ljung-Box test p-value = 0.948) and 1.63 (95% CI: 0.44-2.81; Ljung-Box test p-value = 0.155) up to 2035, respectively. In HRS, males (2007-2023) and non-Hispanics (2018-2021) showed significant upward trends in mortality , with APC of 2.09 (95% CI: 1.58-2.78; p=0.001) and 7.80 (95% CI: 1.81-9.67; p=0.01), respectively. Among those with portal hypertension, females (2010-2023) and Hispanics (2009-2021) displayed significant increases in mortality trends with APC of 7.07 (95% CI: 5.22-10.88; p=0.001) and 5.78 (95% CI: 0.43-11.60; p=0.04), respectively. Whites exhibited significant rising trends in mortality from 2008-2023 with APC of 3.28 (95% CI: 2.85-3.84; p=0.001) in HRS group. Census Region 4: West showed the highest mean AAMRs of 2.81 and 0.76 in HRS and PH group, respectively. Alaska displayed the highest AAMR of 4.2 in HRS group while North Dakota stood highest in PH group with AAMR of 1.4. Conclusion: Our study reported notable disparities , particularly the substantial rise s in APCs of Males and non-Hispanics in HRS group and females and Hispanics in PH- group, highlighting the distinct mortality patterns associated with these conditions. Furthermore, the rising AAMRs predicted by ARIMA suggest the need for targeted interventions and subtle healthcare policies.