Abstract / Summary
Background: Hepatic vascular diseases (HVDs)—encompassing portal inflow, sinusoidal microcirculatory, hepatic venous outflow, and hepatic arterial disorders—cause severe portal hypertension, liver failure, and death. Despite major therapeutic advances, national long-term mortality trends and demographic disparities across this spectrum of diseases remain undefined.
Methods: In this nationwide, population-based serial cross-sectional study, we analyzed CDC WONDER Multiple Cause of Death records for U.S. decedents aged ≥25 years from 1999 through 2024. HVD-related deaths were identified by any mention of primary vascular lesions across the four vascular compartments (ICD-10 codes: I81, K75.1, I82.0, K76.5, K76.4, and K76.3). Age-adjusted mortality rates (AAMRs), standardized to the 2000 U.S. population, and Joinpoint regression models were used to estimate annual percent change (APC) and average annual percent change (AAPC).
Results: Among 22,498 HVD-related deaths, annual fatalities increased 4.7-fold, from 433 in 1999 to 2,025 in 2024, while the AAMR rose from 0.233 to 0.735 per 100,000 (overall AAPC, 4.94% [95% CI, 4.60%–5.24%]). Following a decade of relative stability from 1999 to 2011 (APC, 0.85%), mortality underwent a steep upward inflection during 2011–2024 (APC, 8.87% [95% CI, 8.31%–9.52%]). Portal vein thrombosis (PVT) accounted for 80.8% of all deaths (n = 18,189) and increased rapidly (AAPC, 7.48%); notably, excluding PVT abolished the secular upward trend across the remaining HVDs (AAPC, −0.55% [95% CI, −1.62% to 0.60%]). Concurrent mentions of cirrhosis nearly doubled (19.6% to 35.2%), and co-listing of hepatocellular carcinoma more than tripled (6.5% to 20.1%). Persistent disparities were observed: males had higher mortality than females (rate ratio [RR], 1.52; 95% CI, 1.48–1.56), Hispanic individuals bore the highest racial and ethnic burden (AAMR, 0.434), the West had the highest regional mortality rate (AAMR, 0.460), and nonmetropolitan residents experienced excess mortality compared with metropolitan residents (RR, 1.13; 95% CI, 1.08–1.18). Mortality briefly exceeded pre-pandemic projections only in 2021.
Conclusions: Mortality from hepatic vascular diseases in the United States has escalated rapidly since 2011, driven primarily by portal vein thrombosis amid increasing national burdens of cirrhosis and liver cancer. Marked sex, racial and ethnic, and rural–urban disparities highlight the urgent need for targeted vascular surveillance and equitable access to specialized multidisciplinary hepatology and endovascular care.