Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and the risk of hepatocellular carcinoma: a nationwide cohort study.

Background/Aims:To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort. Methods:Information on study participants were derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. Association of evolutionary changes in MASLD status as assessed by fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using the multivariable-adjusted Cox proportional hazards regression. Results:Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68-3.21; P<0.001), incident (aHR, 1.85; 95% CI, 1.63-2.10; P<0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18-1.50; P<0.001) had an increased risk of HCC than that of persistent non-MASLD. Conclusions:The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.