Prevalence and short-term mortality of acute-on-chronic liver failure: A national cohort study from the USA

•Of 72,316 ethnically diverse patients from 127 Veterans Affairs facilities in the US, 19,082 (26.39%) met ACLF criteria. •Patients with ACLF had high 28- and 90-day mortality (25.52% and 40.02%, respectively). •Mortality risk increased in parallel with the number of OFs, ranging from 17–53% at 28 days and 31–69% at 90 days. •African-American race and being seen at a transplant centre were associated with a lower risk of ACLF mortality. Background & Aims Acute-on-chronic liver failure (ACLF) is characterised by the presence of organ failure in patients with decompensated cirrhosis and is associated with high short-term mortality. However, there are limited data on the prevalence and short-term outcomes of ACLF in patients with cirrhosis seen in the US. We aimed to study the prevalence and risk factors associated with the development and short term mortality in a large cohort of patients in the US. Methods Using the US Department of Veterans Affairs (VA) Corporate Data Warehouse, we identified patients with ACLF during hospitalisation for decompensated cirrhosis at any of the 127 VA hospitals between January 1, 2004, and December 31, 2014. We examined the prevalence of ACLF and variables associated with 28- and 90-day mortality in ACLF, and trends in prevalence and survival over time. Results Of 72,316 patients hospitalised for decompensated cirrhosis, 19,082 (26.4%) patients met the criteria of ACLF on admission. Of these, 12.8% had 1, 10.1% had 2, and 3.5% had 3 or more organ failures. Overall, 25.5% and 40.0% of ACLF patients died within 28 days and 90 days of admission, respectively. Older age, White race, liver cancer, higher model for end-stage liver disease sodium corrected score, and non-liver transplant centre were associated with increased risk of death in ACLF. Over the study period, the prevalence of ACLF decreased, and all grades but ACLF-3 had improvement in survival. Conclusions In a US cohort of hospitalised patients with decompensated cirrhosis, ACLF was common and associated with high short-term mortality. Over a decade, ACLF prevalence decreased but survival improvement of ACLF-3 was not seen. Early recognition and aggressive management including timely referral to transplant centres may lead to improved outcomes in ACLF. Lay summary Acute-on-chronic liver failure (ACLF) is a condition marked by multiple organ failures in patients with cirrhosis and associated with a high risk of death. In this study of US patients hospitalised with cirrhosis, 1 in 4 patients developed ACLF. In total, 25% of patients with ACLF died within 1 month and 40% died within 3 months. Thus, early recognition of ACLF is important for the initiation of aggressive management, which is required to save these patients’ lives. Acute-on-chronic liver failure (ACLF) is characterised by the presence of organ failure in patients with decompensated cirrhosis and is associated with high short-term mortality. However, there are limited data on the prevalence and short-term outcomes of ACLF in patients with cirrhosis seen in the US. We aimed to study the prevalence and risk factors associated with the development and short term mortality in a large cohort of patients in the US. Using the US Department of Veterans Affairs (VA) Corporate Data Warehouse, we identified patients with ACLF during hospitalisation for decompensated cirrhosis at any of the 127 VA hospitals between January 1, 2004, and December 31, 2014. We examined the prevalence of ACLF and variables associated with 28- and 90-day mortality in ACLF, and trends in prevalence and survival over time. Of 72,316 patients hospitalised for decompensated cirrhosis, 19,082 (26.4%) patients met the criteria of ACLF on admission. Of these, 12.8% had 1, 10.1% had 2, and 3.5% had 3 or more organ failures. Overall, 25.5% and 40.0% of ACLF patients died within 28 days and 90 days of admission, respectively. Older age, White race, liver cancer, higher model for end-stage liver disease sodium corrected score, and non-liver transplant centre were associated with increased risk of death in ACLF. Over the study period, the prevalence of ACLF decreased, and all grades but ACLF-3 had improvement in survival. In a US cohort of hospitalised patients with decompensated cirrhosis, ACLF was common and associated with high short-term mortality. Over a decade, ACLF prevalence decreased but survival improvement of ACLF-3 was not seen. Early recognition and aggressive management including timely referral to transplant centres may lead to improved outcomes in ACLF.