Beyond hepatitis: the growing burden of alcohol and MASLD in liver cancer mortality

Abstract Background Liver cancer mortality is increasing in the United States, driven by evolving risk factors. While hepatitis C virus was historically the leading cause, alcohol use and metabolic-associated steatohepatitis are now major contributors. Methods A retrospective cohort analysis was conducted using the Global Burden of Disease 2021 database to assess liver cancer mortality by etiology from 2010–2021. Joinpoint regression identified significant shifts in mortality trends ( P < 0.05). Results Between 2010 and 2021, U.S. liver cancer mortality rose by 53%. Hepatitis C and alcohol use accounted for 39.7% and 29.9% of liver cancer deaths in 2021, respectively. Liver cancer deaths rose by 32.14% from 2010–2016 but slowed to 15.81% from 2016–2021 ( P = 0.0082). Mortality from hepatitis C increased by 32.77% (4.84% AAGR) from 2010–2016 but slowed to 15.15% (2.86% AAGR) from 2016–2021 ( P = 0.0195). Hepatitis B-related mortality declined from 24.72% (3.75% AAGR) in 2010–2016 to 7.12% (1.38% AAGR) in 2016–2021 ( P = 0.0001). Alcohol-related deaths rose by 34.52% (5.07% AAGR) from 2010–2016, tapering to 20.01% (3.72% AAGR) from 2016–2021 ( P = 0.0122). Deaths attributed to MASH increased by 26.64% (8.19% AAGR) from 2010–2013, followed by slower growth of 24.80% (2.81% AAGR) from 2013–2021 ( P = 0.1178). Mortality from other causes rose by 25.16% (3.81% AAGR) in 2010–2016 and by 19.03% (3.55% AAGR) in 2016–2021 ( P = 0.0059). Conclusion Declines in hepatitis-related mortality reflect progress in antiviral treatment. However, persistently rising alcohol- and MASH-related deaths highlight the urgent need for public health strategies targeting modifiable risk factors such as alcohol use and obesity.