Mortality, Hepatic Decompensation, and Cardiovascular- and Renal-Related Outcomes in Lean Versus Non-lean Patients Hospitalized With Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is an important cause of cirrhosis and end-stage liver disease. In addition, there have been reports of worse extrahepatic outcomes, especially cardiovascular events, in patients with lean patients' fatty liver disease compared to the non-lean group. There is limited data on hepatic, cardiac, and renal outcomes in lean compared to non-lean patients with MASH. This study aims to evaluate the cardiovascular, renal, and hepatic outcomes in hospitalized US adults with MASH, focusing on a comprehensive comparison between lean and non-lean patients. Methods: The National Inpatient Sample (NIS) database was queried from 2016 to 2020 to identify hospitalizations with MASH. Hospitalizations with a history of overweight and obesity (lean body mass index (BMI) <25 vs. lean BMI >25) were also identified. The primary outcome was in-hospital mortality. Secondary outcomes were major adverse cardiovascular outcomes (MACE: a composite of acute myocardial infarction, cardiac arrest, stroke, heart failure, and atrial fibrillation); major adverse kidney outcome (MAKE: a composite outcome of acute kidney injury (AKI), renal replacement therapy, and renal cancer), and hepatic decompensation (esophageal varices with bleeding, ascites, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, and hepatorenal syndrome) Multivariate logistic regression analysis was used to derive risk ratios for clinical outcomes. Results: We included 539,275 MASH patients in our sample; 324,330 (60%) were lean. The included patients were mostly female (61%), the mean age was 64 years, and 76% were White. At baseline, non-lean patients had a higher prevalence of heart failure, hypertension, and hyperlipidemia. There was no difference in the prevalence of smoking among both groups. In a multivariate analysis, with adjustment for age, sex, race, sarcopenia, cardiometabolic risk factors, hospital characteristics, admission type, socioeconomic factors, and all comorbidities (including 31 Elixhauser comorbidities), lean status was associated with a 40% increased risk of mortality (adjusted odds ratio (aOR) 1.40, confidence interval (CI) 1.29-1.53), 19% increased risk of MACE (aOR 1.19; 95% CI 1.14-1.24), 20% increased risk of renal decompensation (aOR 1.25; 95% CI 1.20-1.30), and 33% increased risk of hepatic decompensation (aOR 1.33 CI 1.28-1.38). Conclusion: Lean patients with MASH are at higher risk of cardiovascular and renal outcomes and may benefit from enhanced screening for early identification and treatment to improve outcomes.