Editorial: Liver and Non‐Liver Outcomes Between Different Subtypes of Steatotic Liver Disease

Steatotic liver disease (SLD) is the most prevalent liver non-communicable disease affecting more than one-third of the global population. With the new nomenclature proposed in recent years by the major societies, the elucidation of the disease course and outcomes of SLD is a mandatory task clinically [1, 2]. The specific question is: How're the differences of liver and cardiovascular outcomes between the major subtypes of SLD? The elucidation provides not only an effective risk stratification of the heterogeneous metabolic disorder, but also helps in paving the way for optimal patient management. In this issue Miwa et al., investigated both major adverse liver outcome (MALO), major adverse cardiovascular event (MACE) and all-cause mortality of different subtypes of SLD by using a large-scale open database [3]. The cohort study of long follow-up period tracked outcomes through hospital records and death registries in the UK. The major findings were: (1) There was a clear graded risk progression of MALO, ranging from hazard ratios (HR) 1.23 of metabolic and alcohol-associated liver disease (MetALD) to HR 2.95 of alcohol-associated liver disease (ALD) compared to metabolic dysfunction-associated steatotic liver disease (MASLD); (2) The ALD group had a higher risk of both MACE (HR 1.17) and death (HR 1.52) compared to MASLD, whereas the risks for MACE and all-cause mortality were similar between MASLD and MetALD. The novelty of the investigation lies in its validation and clinical characterisation of the new SLD nomenclature on a massive scale, specifically highlighting the impact of alcohol use. The findings demonstrated that individuals with ALD had a substantially higher risk of death compared with both MASLD and MetALD, underscoring the severe survival disadvantage associated with ALD in the general population. It also suggested that alcohol and metabolic dysfunction act synergistically to accelerate liver damage. In addition, the study consistently demonstrated that diabetes and baseline fibrosis stage were universal predictors of poor outcomes across all subtypes of SLD [4]. Some works remain for further validation of the implications the study demonstrated. First, the UK Biobank cohort mainly recruited relatively healthy individuals aged 40–69 years, who were wealthier, had a lower prevalence of diabetes, and were more likely to be female than the general population. In that case, it may limit the generalisability of the risks, even yielding potential underestimation of absolute risks. Second, alcohol consumption was documented in self-reported questionnaires at baseline, whereas lifestyle factors and cardiometabolic risk factors (CMRFs) were also reported only at baseline. The potential bias may limit the ability to account for the potential changes of drinking behaviours or interventions of CMRFs by cardiometabolic drugs during the long-term observation period. Moreover, potential and possible transitions between SLD subtypes over time may affect SLD progression and outcomes. Collectively, this study provides novel clues for the understanding of the natural course of SLD. It also serves as a benchmark of population-level risk stratification for personalised interventions. The exploration is helpful in constructing an evidence-based patient care guidance across ethnicity, gender, and aetiologies [5]. Jee-Fu Huang: conceptualization, writing – original draft, writing – review and editing. Ming-Lung Yu: writing – review and editing, project administration. Wan-Long Chuang: writing – review and editing, funding acquisition. This work was supported by Kaohsiung Medical University Hospital (Grant KMUH-DK(B)114004-1) and Kaohsiung Medical University (Grant KMU-TC114A08). Jee-Fu Huang consultant for Roche, Sysmex, Boehringer Ingelheim, Novo Nordisk, and Aligos. Speaker for Abbvie, Gilead, Merck, Sysmex, Boehringer Ingelheim, and Novo Nordisk. Ming-Lung Yu research grant from Abbott, BMS, Merck, and Gilead; Consultant of Abbvie, Abbott, Ascletis, BMS, Merck, Gilead, and Roche; Speaker for Abbvie, Abbott, BMS, Merck, Gilead, and IPSEN. Wan-Long Chuang consultant of Gilead, AbbVie, BMS, and PharmaEssentia; Speaker for Gilead, AbbVie, BMS, and PharmaEssentia. This article is linked to Miwa et al. papers. To view this article, visit https://doi.org/10.1111/apt.70711. The data that support the findings of this study are available from the corresponding author upon reasonable request.