MAFLD but not MASLD increases risk of all-cause mortality in regional Australia, with components of metabolic syndrome exacerbating factors: 20 year longitudinal, cohort study

Karl Vaz; William Kemp; Ammar Majeed; John Lubel; Dianna J Magliano; Kristen M Glenister; Lisa Bourke; David Simmons; Stuart K Roberts

doi:10.1007/s12072-024-10748-5

MAFLD but not MASLD increases risk of all-cause mortality in regional Australia, with components of metabolic syndrome exacerbating factors: 20 year longitudinal, cohort study

Hepatol Int. 2024 Dec 14. doi: 10.1007/s12072-024-10748-5. Online ahead of print.

Authors

Karl Vaz^{1

2}, William Kemp^{3

4}, Ammar Majeed^{3

4}, John Lubel^{3

4}, Dianna J Magliano⁵, Kristen M Glenister⁶, Lisa Bourke⁶, David Simmons^#^{6

7}, Stuart K Roberts^#^{3

4}

Affiliations

¹ Department of Gastroenterology and Hepatology, Alfred Health, Ground Floor Alfred Centre,55 Commercial Road, Melbourne, VIC, 3004, Australia. k.vaz@alfred.org.au.
² Central Clinical School, Monash University, Melbourne, VIC, Australia. k.vaz@alfred.org.au.
³ Department of Gastroenterology and Hepatology, Alfred Health, Ground Floor Alfred Centre,55 Commercial Road, Melbourne, VIC, 3004, Australia.
⁴ Central Clinical School, Monash University, Melbourne, VIC, Australia.
⁵ Diabetes and Population Health, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
⁶ Department of Rural Health, University of Melbourne, Parkville, VIC, Australia.
⁷ Macarthur Clinical School, School of Medicine, Western Sydney University, Penrith, NSW, Australia.

^# Contributed equally.

PMID: 39673677
DOI: 10.1007/s12072-024-10748-5

Abstract

Background and aims: Controversy remains whether the mortality risk in people with fatty liver disease (FLD) including metabolic-(dysfunction) associated steatotic liver disease (MASLD) and metabolic-(dysfunction) associated fatty liver disease (MAFLD) is higher than observed in those without FLD. We aimed to determine the mortality rate and mortality rate ratio (MRR) for these FLDs.

Methods: The study population was a randomly selected cohort of community-dwelling adults in regional Victoria, Australia between 2001 and 2003 with sufficient data evaluable for Fatty Liver Index and determination on alcohol consumption. MASLD and MAFLD were diagnosed by established criteria. The primary outcome was overall mortality and main secondary outcome was major adverse liver outcomes (MALO) (i.e., decompensated liver disease, primary liver cancer and liver-related death). Non-fatal and fatal outcomes were captured via data linkage to hospital admission, cancer registry, and death registries. MRR was calculated with non-FLD participants as the comparator.

Results: 1444 (99.3%) and 1324 (91.1%) individuals from a total of 1454 were included in the final MAFLD and MASLD analyses. The median follow-up was 19.7 years (IQR 19.1-20.1) and there were 298 deaths. The MRR for MAFLD and MASLD was 1.39 (95% CI 1.10-1.76) and 1.25 (95% CI 0.96-1.61), respectively. MAFLD persisted as a risk factor for all-cause death on multivariable models correcting for lifestyle and socioeconomic variables, but not when adjusted for metabolic risk factors. MALOs were increased in MAFLD [incidence rate ratio (IRR) 3.03, 95% CI 1.22-8.18] and MASLD (IRR 2.80, 95% CI 1.05-7.90). Metabolic risk factors increased the risk of overall mortality and MALO, and cancer (34.3-34.6%) and cardiovascular disease (30.1-33.7%) were the most common cause of death in FLD.

Conclusion: In this population-based longitudinal study, MAFLD but not MASLD increases the risk of overall mortality, with metabolic syndrome components key risk factors increasing risk of death.

Keywords: MAFLD; MASLD; Major adverse liver outcome; Metabolic syndrome; NAFLD; Overall mortality.