S2635 Rising Trends and Mortality Predictors in MASLD-Associated Cirrhosis: A Nationwide Analysis

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the leading cause of chronic liver disease, driven by rising rates of obesity, diabetes, and metabolic syndrome. As MASLD-related cirrhosis becomes more prevalent, hospitalizations and complications such as hepatic encephalopathy and acute-on-chronic liver failure (ACLF) are increasing. Yet, outcome data specific to MASLD-cirrhosis remain limited. This study analyzes national trends, complication rates, and in-hospital mortality predictors in MASLD-associated cirrhosis using a large, representative inpatient dataset. Methods: A retrospective analysis of the National Inpatient Sample (2018–2022) was conducted. Adult hospitalizations with cirrhosis were identified and stratified by MASLD etiology using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Outcomes included in-hospital mortality and complications such as acute-on-chronic liver failure (ACLF), hepatic encephalopathy (HE), and hepatocellular carcinoma (HCC). Weighted logistic regression identified independent mortality predictors. Results: Out of 2.1 million cirrhosis-related hospitalizations, 303,210 (14.4%) involved MASLD. Between 2018 and 2022, ACLF cases in MASLD patients increased by 180% (from 1,565 to 4,385). Despite rising complication rates, in-hospital mortality for MASLD-cirrhosis remained consistently lower than non-MASLD cirrhosis (1.10% vs 1.40% in 2022). Multivariate analysis identified adrenal insufficiency (OR 1.75, 95% CI: 1.25–2.45) and congestive heart failure (OR 1.10, 95% CI: 1.00–1.21) as significant predictors of inpatient death. Interestingly, comorbid obesity (OR 0.88), hypertension (OR 0.66), and dyslipidemia (OR 0.62) were independently associated with reduced mortality risk. Conclusion: Despite rising rates of ACLF and other complications, MASLD-cirrhosis patients demonstrated lower inpatient mortality than those with other cirrhosis etiologies. This paradox may reflect earlier detection, differing comorbidity profiles, or improved inpatient management of MASLD-related complications. Notably, adrenal insufficiency emerged as a strong and under-recognized risk factor for mortality, suggesting a gap in current diagnostic and treatment protocols. The identification of CHF as another independent predictor underscores the role of cardiovascular-metabolic interplay in MASLD outcomes. These findings support enhanced inpatient vigilance and multidisciplinary evaluation, including endocrine assessment.