Escalating mortality and widening disparities in metabolic dysfunction-associated steatotic liver disease and related hepatocellular carcinoma in the US, 1999–2020

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing cause of liver-related mortality, yet long-term, population-based mortality trends on demographic disparities remain poorly characterized. This study analyzed mortality trends for MASLD and MASLD-related hepatocellular carcinoma (HCC) in the United States from 1999 to 2020 using the CDC WONDER database. We identified 72,647 MASLD-related deaths and 1,678 MASLD-related HCC deaths among adults aged ≥ 25 years. The age-adjusted mortality rate (AAMR) for MASLD nearly tripled, increasing from 1.07 to 3.11 per 100,000 population (AAPC: 5.05%). The rise was significantly steeper for MASLD-related HCC between 2011 and 2020 (AAPC: 18.30%). Subgroup analyses revealed widening disparities: mortality rates accelerated most rapidly among Black populations and in rural regions, where the AAMR surpassed that of urban areas by 2015. Additionally, a reversal in gender trends was observed, with female mortality rates exceeding those of males after 2013. These findings indicate a shifting MASLD epidemiological burden toward Black populations, rural communities and women. Public health policy must pivot from specialty-based care to integrated primary care models, specifically by integrating liver disease screening into rural primary care and incorporating liver health metrics into national metabolic management guidelines to mitigate these inequities.