Steatotic liver disease subtypes and risk of hospitalization for sepsis: a nationwide cohort study

Background The recent reclassification of steatotic liver disease (SLD) into metabolic dysfunction-associated SLD (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-related liver disease (ALD) provides a clinically relevant framework for distinguishing heterogeneous etiologic subtypes. However, whether these newly defined SLD subtypes differ in their susceptibility to sepsis remains unclear. We assessed the incidence and risk of hospitalization for sepsis across the SLD spectrum in a nationwide cohort.Methods We conducted a retrospective cohort study using the Korean National Health Insurance Service database, including 4,389,734 adults who underwent health screening in 2012. SLD was defined as a fatty liver index (FLI) ≥30 and subtyped as MASLD, MetALD, or ALD based on cardiometabolic risk profiles and alcohol intake; FLI <30 defined the non-SLD reference group. Sepsis was identified using hospitalization claims and ICD-10 codes from 2013 to 2022. Adjusted hazard ratios (aHRs) were estimated using multivariable Cox proportional hazards models, with subgroup and sensitivity analyses.Results The cohort comprised MASLD (n = 1,332,944; 30.4%), MetALD (n = 164,387; 3.7%), and ALD (n = 79,445; 1.8%). Sepsis incidence per 1,000 person-years was 3.11, 2.25, and 4.49, respectively, compared with 2.20 in the non-SLD group. After adjusting for established sepsis risk factors, all subtypes remained associated with higher risk, greatest in ALD (aHR 1.53), followed by MetALD (1.11) and MASLD (1.07) (all p < 0.001). MetALD showed lower crude incidence than MASLD but a higher adjusted risk in multivariable models. In sensitivity analyses restricted to individuals without comorbidities, associations persisted: ALD (aHR 1.60), MetALD (1.16), and MASLD (1.09) (all p < 0.001).Conclusions All SLD subtypes were associated with increased but distinct risks of hospitalization for sepsis, with ALD conferring the highest risk. These findings support subtype-specific risk stratification and may inform infection-prevention strategies and clinical surveillance in individuals with SLD.