Incidence and Mortality of Acute‐on‐Chronic Liver Failure Using Two Definitions in Patients with Compensated Cirrhosis

Abstract

The term acute-on-chronic liver failure (ACLF) is intended to identify patients with chronic liver disease who develop rapid deterioration of liver function and high short-term mortality after an acute insult. The two prominent definitions (European Association for the Study of the Liver [EASL] and Asian Pacific Association for the Study of the Liver [APASL]) differ, and existing literature applies to narrow patient groups. We sought to compare ACLF incidence and mortality among a diverse cohort of patients with compensated cirrhosis, using both definitions. This was a retrospective cohort study of patients with incident compensated cirrhosis in the Veterans Health Administration from 2008 to 2016. First ACLF events were identified for each definition. Incidence rates were computed as events per 1,000 person-years, and mortality was calculated at 28 and 90 days. Among 80,383 patients with cirrhosis with 3.35 years median follow-up, 783 developed EASL and APASL ACLF, 4,296 developed EASL ACLF alone, and 574 developed APASL ACLF alone. The incidence rate of APASL ACLF was 5.7 per 1,000 person-years (95% confidence interval [CI]: 5.4-6.0), and the incidence rate of EASL ACLF was 20. 1 (95% CI: 19.5-20.6). The 28-day and 90-day mortalities for APASL ACLF were 41.9% and 56.1%, respectively, and were 37.6% and 50.4% for EASL ACLF. The median bilirubin level at diagnosis of EASL-alone ACLF was 2.0 mg/dL (interquartile range: 1.1-4.0). Patients with hepatitis C or nonalcoholic fatty liver disease had among the lowest ACLF incidence rates but had the highest short-term mortality. Conclusion: There is significant discordance in ACLF events by EASL and APASL criteria. The majority of patients with EASL-alone ACLF have preserved liver function, suggesting the need for more liver-

Mixed Fibrinolytic Phenotypes in Decompensated Cirrhosis and Acute‐on‐Chronic Liver Failure with Hypofibrinolysis in Those With Complications and Poor Survival

“…Patients with acute decompensation of cirrhosis (AD) or acute‐on‐chronic liver failure (ACLF) have progressive changes in their hemostatic system and are at particular risk for bleeding and thrombotic complications . Patients with ACLF are characterized by development of organ failure and high short‐term mortality . An intense systemic inflammatory response that is often complicated (or precipitated) by infection is one of the hallmarks of ACLF .…”

Letter to the Editor: Tale of Two ACLF Definitions: Choices Are Getting Clearer

“…The median bilirubin and creatinine at presentation in the EASL-defined cohort were around 2 mg/dL each, and the 28-day mortality was 37%. (3) The median bilirubin and creatinine using APASL criteria were 6.5 mg/dL and 0.8 mg/dL, respectively, with a 28-day mortality of 40%. The causes of death would be different.…”

“…Likewise, Mahmud et al state that APASL criteria identify high short-term mortality events with liver-specific injury, whereas the EASL criteria identify nonhepatotropic causes. (3) In fact, the most commonly identified organ failure EASL grade was the kidney, whereas liver was the most infrequent. Indeed, a patient with cirrhosis may have three organ failures (circulatory, pulmonary, and renal) with normal bilirubin, and die.…”

Reply:

“…We appreciate the interest in our manuscript evaluating and comparing the characteristics of Asian Pacific Association for the Study of the Liver (APASL) acute-on-chronic liver failure (ACLF) and European Association for the Study of the Liver (EASL) ACLF definitions in a large cohort of diverse patients with chronic liver disease (1) and would like to respond to several queries raised by the hepatology community. First, Choudhury et al echo our concern that EASL ACLF, which provides multiple pathways to meet criteria based on organ failures (OFs), is nonspecific and identifies many patients with high-mortality events who ultimately die with near-normal liver labs.…”

“…We would like to congratulate Zhou et al (1) for performing the largest meta-analysis to date on nonalcoholic fatty liver disease (NAFLD) in China. However, we have several concerns with their findings because of the methods they used to determine and report the prevalence.…”