The North American Consortium for the Study of End-Stage Liver Disease's definition of acute-on-chronic liver failure (NACSELD-ACLF) as two or more extrahepatic organ failures has been proposed as a simple bedside tool to assess the risk of mortality in hospitalized patients with cirrhosis. We validated the NACSELD-ACLF's ability to predict 30-day survival (defined as in-hospital death or hospice discharge) in a separate multicenter prospectively enrolled cohort of both infected and uninfected hospitalized patients with cirrhosis. We used the NACSELD database of 14 tertiary care hepatology centers that prospectively enrolled nonelective hospitalized patients with cirrhosis (n = 2,675). The cohort was randomly split 60%/40% into training (n = 1,605) and testing (n = 1,070) groups. Organ failures assessed were (1) shock, (2) hepatic encephalopathy (grade III/IV), (3) renal (need for dialysis), and (4) respiratory (mechanical ventilation). Patients were most commonly Caucasian (79%) men (62%) with a mean age of 57 years and a diagnosis of alcohol-induced cirrhosis (45%), and 1,079 patients had an infection during hospitalization. The mean Model for End-Stage Liver Disease score was 19, and the median Child score was 10. No demographic differences were present between the two split groups. Multivariable modeling revealed that the NACSELD-ACLF score, as determined by number of organ failures, was the strongest predictor of decreased survival after controlling for admission age, white blood cell count, serum albumin, Model for End-Stage Liver Disease score, and presence of infection. The c-statistics were 0.8073 for the training set and 0.8532 for the validation set. Conclusion: Although infection status remains an important predictor of death, NACSELD-ACLF was independently validated in a separate large multinational prospective cohort as a simple, reliable bedside tool to predict 30-day survival in both infected and uninfected patients hospitalized with a diagnosis of cirrhosis. (Hepatology 2018;67:2367-2374).
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