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

Abstract

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.

Keywords: Hepatic decompensation; Lean; Mortality; Non-alcoholic steatohepatitis; Non-lean.

Fig. 1

Temporal Trends in Lean and Non-Lean MASLD Diagnosis

Fig. 2

BMI Trajectory During Pre-Baseline and Study Follow-up for Lean and Non-Lean MASLD Cirrhosis Patients

Fig. 3

Unadjusted Kaplan–Meier Failure Curves and Adjusted Cumulative Incidence Function Curves for Primary and Secondary Outcomes for Lean and Non-Lean MASLD Cirrhosis

Fig. 4

Sensitivity Analyses* for Primary and Secondary Outcomes. *Primary models adjust for age, sex, race, history of diabetes mellitus, MELD-Na, smoking status, and time-updated AUDIT-C. Sensitivity analysis 1 (sens. 1) additionally adjusts for history of coronary artery disease, heart failure, cerebrovascular accident. Sensitivity analysis 2 additionally adjusts for baseline use of metformin, insulin, selective beta blockers, non-selective beta blockers, statins, distal tubule diuretics, and loop diuretics. Sensitivity analysis 3 additionally limits the cohort to patients with diabetes at baseline. Sensitivity analysis 4 additionally restricts the cohort to patients with 2 or more outpatient VHA visits in the year prior to the index date. ** Decompensation and MACE hospitalization outcomes models account for competing risk of liver transplantation and death

Fig. 5

Cause-Specific Hazard Analysis for Liver-Related, CV-Related, and Non-Liver/Non-CV-Related Mortality

Fig. 6

Exploratory Analysis of ICD-10 Cause of Death Category Data by Lean Status*. * Data available for 24.4% of cohort deaths