Dynamic Transitions in Steatotic Liver Disease Subtypes and Risk of Liver-Related Events: A Nationwide Cohort Study

Introduction: Although steatotic liver disease (SLD) is a dynamic condition, the prognostic impact of subtype transitions over time remains unclear. We investigated the association between SLD subtype transitions and the risk of long-term liver-related events (LREs). Methods: From the Korean National Health Insurance Service database, adults who underwent national health checkups in both 2015 and 2017 were recruited. SLD subtypes included metabolic dysfunction-associated SLD, metabolic and alcohol-related SLD, and alcohol-related liver disease. Transitions were classified into no transitions, transitions to more advanced subtypes, and transitions to less advanced subtypes. LREs included incident cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related mortality. Subdistribution hazard ratios (sHRs) were estimated using Fine-Gray competing-risk models. Results: Among 1,988,878 individuals, 21.7% transitioned over two years: 11.3% transitioned to more advanced subtypes, whereas 10.4% transitioned to less advanced subtypes. In each SLD subtype, transitions to more advanced subtypes showed a higher risk of LREs, whereas transitions to less advanced subtypes showed a lower risk of LREs. In SLD, the transitions to more advanced subtypes showed a higher risk of LREs (sHR, 1.34; 95% confidence interval [CI], 1.28-1.40), whereas transitions to less advanced subtypes showed a lower risk (sHR, 0.86; 95% CI, 0.83-0.88). Sensitivity analyses stratified by sex, BMI, and a fatty liver index threshold of >60 demonstrated comparable findings. Conclusion: We found that transitions to more advanced SLD subtypes showed increased risks of LREs, whereas transitions to less advanced subtypes showed risk reduction. The findings highlight the need for management schemes considering SLD subtype changes over time.