Alcohol–Related Liver Disease, Followed by Metabolic Dysfunction–Associated Steatotic Liver Disease, Emerges as the Fastest‐Growing Aetiologies for Primary Liver Cancer in the United States

ABSTRACT Objective Primary liver cancer (PLC) is projected to be the third leading cause of cancer mortality in the United States in 2040. We examine the burden of PLC in the United States, stratified by sex, state and aetiological risk factors. Methods Data on PLC prevalence, incidence, death and disability–adjusted life years (DALYs) were extracted from the Global Burden of Disease Study 2021. Changes in these parameters were calculated using the Joinpoint regression model. Results There were 47,970 cases, 31,450 incident cases, 24,770 deaths and 576,920 DALYs from PLC in the United States. The highest prevalence (16,980), incidence (12,040), death (9840) and DALYs (213,410) from PLC were due to chronic hepatitis C virus infection. From 2000 to 2021, PLC incidences increased by 141%, and PLC deaths increased by 136%. Age–standardised incidence rates (ASIRs) and death rates (ASDRs) per 100,000 population for PLC increased, primarily driven by alcohol–related liver disease (ALD) (ASIR: annual percent change [APC]: +2.40%; ASDR: APC: +2.22%) and metabolic dysfunction–associated steatotic liver disease (MASLD) (ASIR: APC: +2.32%; ASDR: APC: +2.04%). Conclusion The burden of PLC in the United States has risen in the past two decades, driven mainly by ALD and followed by MASLD. These findings offer policymakers an accurate assessment of the PLC burden and emphasise the need for targeted risk factor mitigation, especially regarding alcohol related policy.