S2926 Trends and Predictors of Acute-on-Chronic Liver Failure Among Cirrhosis-Related Hospitalizations in the United States: An Updated Nationwide Analysis

Introduction: Acute-on-chronic liver failure (ACLF) is a critical condition marked by acute deterioration in cirrhosis with multi-system organ failure, leading to high morbidity and mortality. Despite reports of increasing cirrhosis prevalence, contemporary data on rates of ACLF and etiological trends remain scarce. Methods: Using the National Inpatient Sample (2016–2020), we identified adult patients admitted for cirrhosis-related conditions and categorized them by etiology: viral-related, alcohol-related (ALD), nonalcoholic steatohepatitis (NASH), and other causes. ACLF was defined as cirrhosis with ≥2 organ system failures: respiratory failure requiring mechanical ventilation, shock, grade ≥3 hepatic encephalopathy, or renal failure requiring dialysis/replacement therapy. Trends in ACLF rates were analyzed using Cochrane-Armitage test and multivariable logistic regression identified predictors of ACLF among etiology, demographics and comorbidities (Charleson Comorbidity Index [CCI]) while using hospital characteristics as confounders. Results: A total of 690,481 adult hospitalizations were included with 4.7% (n = 32,311) meeting the criteria for ACLF. The mean age was 60 years (SEM, ± 8) with 61% men and 62% non-Hispanic White. The highest proportion of ACLF was in ALD (6%), followed by other causes (3.9%), viral-related (3.6%) and NASH-related (3.5%). Similarly, respiratory failure (82%) and shock (82%) were the most common organ system failures followed by renal failure (40%) and hepatic encephalopathy (20%). The rates of ACLF significantly increased from 2016 to 2020 (4.53% vs 5.16%, P < 0.001). This trend was also observed across all etiologies with the most increase in ACLF arising from other causes (3.74% vs 4.42%, P < 0.001). Among various predictors, ALD (OR [95% CI] : 1.9 [1.83-1.98]), other causes (OR [95% CI] : 1.20 [1.15-1.25]), female sex (OR [95% CI] : 1.03 [1.01-1.06]), African-American race (AA) (OR [95% CI] : 1.22[1.17-1.27]), other races (OR [95% CI] : 1.25 [1.19-1.31]), CCI 4-6 (OR [95% CI]: 1.71 [1.65-1.77]) and CCI ≥7 (OR [95% CI] : 2.47 [2.37-2.57]) were significantly associated with increasing odds of developing ACLF. Conclusion: The rates of ACLF in cirrhosis-related hospitalizations continues to rise in the US with significant increases noted across all etiologies. Factors like ALD, female sex, AA race, and comorbidity burden are associated with higher odds of ACLF. The causal implication of these factors needs to be further studied.