Mortality, Hepatic Decompensation, and Cardiovascular Outcomes in Lean vs. Non-lean MASLD Cirrhosis: A Veterans Affairs Cohort Study

Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) has a global prevalence of 25%. Studies on incident liver and cardiovascular outcomes in lean (Body mass index: BMI < 25 kg/m², or < 23 kg/m² for Asians) vs. non-lean individuals with MASLD have reported mixed results. We aimed to compare incident clinical outcomes and mortality between lean and non-lean individuals with compensated MASLD cirrhosis in a large national cohort.

Methods: This was a retrospective cohort study of patients with newly diagnosed compensated MASLD cirrhosis in the Veterans Health Administration between 01/2008 and 05/2021. The primary outcome was incident hepatic decompensation, and secondary outcomes were incident major adverse cardiovascular events (MACE) and all-cause mortality. Multivariable Cox proportional hazard models were used to assess association. Fine and Gray competing risk regression was used where applicable.

Results: The study included 15155 patients with MASLD cirrhosis: 1,597 lean and 13558 non-lean patients. Included patients were mostly male (95%), median age was 67 years, and 72.8% were non-Hispanic white. At baseline, the prevalence of diabetes was lower in lean vs. non-lean individuals (46.7 vs. 73.9%, p < 0.001). In multivariable models, lean status was associated with a 64% increased risk of all-cause mortality (aHR = 1.64) but decreased risk of hepatic decompensation (aSHR = 0.67). Lean individuals experienced significantly higher rates of cardiovascular-related mortality (aHR = 1.40).

Conclusion: Lean MASLD patients with compensated cirrhosis had a higher mortality risk but a lower risk of hepatic decompensation than non-lean patients. Despite having a better baseline cardiometabolic profile and similar rates of MACE, lean individuals with MASLD cirrhosis have a higher risk of cardiovascular mortality.