Risk of all-cause mortality and adverse outcomes from steatotic liver disease and its subgroups in the general population

Background and Aims: With the implementation of the new nomenclature on steatotic liver disease (SLD), three main subgroups consisting of metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with increased alcohol intake (MetALD), and alcohol-related liver disease (ALD) have been defined. However, the risk of SLD for all-cause mortality and adverse outcomes as well as the different risks between MASLD, MetALD, and ALD needs further clarification.

Methods: Data from 13,599 participants of the population-based Gutenberg Health Study were cross-sectionally and prospectively analysed. The fatty liver index (FLI) with a score of ≥60 was used to define SLD. The subgroups of SLD were defined according to the new nomenclature. The fibrosis-4 score (FIB-4) was calculated to determine patients at risk of fibrosis (≥1.3). All-cause mortality and several adverse outcomes were analysed and compared across the subgroups of SLD. Cox regression models were used to estimate adjusted hazard ratios (aHR) and their 95% confidence intervals (CIs). Adjustments were made for age, sex, socioeconomic status, education, and smoking.

Results: The overall prevalence of SLD was 37.3% (n=5,074), and the prevalence of MASLD, MetALD, and ALD were 30.5% (n=4,154), 5.3% (n=717) and 1.5% (n=202), respectively. Almost half of the population were women (48.9%), and the mean age was 54.3(±11.0) years. An elevated FIB-4 ≥1.3 was present in 20.2% with SLD. The cumulative incidence of all-cause mortality was higher in SLD and all its subgroups compared to no SLD (p<0.0001) ([Fig. 1]). Stratification by FIB-4 ≥1.3 revealed a higher risk of all-cause mortality across all investigated SLD subgroups compared to FIB-4 <1.3 (p<0.0001). Each subgroup of SLD was associated with a higher risk of all-cause mortality (MASLD: aHR 1.6, 95%CI 1.4-1.9; MetALD: aHR 1.6, 95%CI 1.3-2.1; ALD: aHR 1.6 95%CI 1.0-2.5). The risk of adverse outcomes was increased in MASLD (hepatic decompensation: aHR 1.2, 95% CI 1.0-1.5; major adverse cardiac events: aHR 1.5, 95%CI 1.2-1.8), whereas no differences were seen for MetALD and ALD.

Fig. 1  

Conclusion: The prevalence of SLD and especially MASLD is high in the general population. Patients with SLD and any of its three main subgroups show a higher risk of all-cause mortality, whereas the risk for adverse outcomes is particularly increased in those with MASLD. These results highlight the importance of screening for SLD and related risk factors to improve outcomes.

Publication History

Article published online:
26 September 2024