Epidemiological Characteristics of Acute‐on‐Chronic Liver Failure in Patients With Compensated Liver Disease: A Systematic Review and Meta‐Analysis

ABSTRACT Aims Acute‐on‐chronic liver failure (ACLF) frequently develops in patients with compensated liver disease. We aimed to characterize the epidemiological features and mortality rates of ACLF in this population and their changes over time. Methods We performed a meta‐analysis of cohort studies on patients with ACLF and compensated liver disease to evaluate pooled baseline characteristics and mortality rates. Literature searches were conducted using EMBASE, PubMed, and the Cochrane Library, covering the period from January 1, 2012, to December 31, 2023. Following Freeman–Tukey double arcsine transformation, pooled estimates of mortality rates and etiological distributions were derived using a random‐effects model. Subgroup analyses were performed according to country and period (pre‐ and post‐2014). Results Twenty‐four studies involving 4,398 patients were included. The mean age was 48.7 years and 80.4% (3017/3824) were men, after excluding one study based on veterans. The mean Model for End‐Stage Liver Disease score was 24.0. Viral hepatitis (42.2%, 2070/4398) and alcohol‐related liver disease (ALD) (35.6%, 1328/4283) were the major etiologies of underlying chronic liver disease. Flare‐ups of viral hepatitis (24.6%, 788/2263) and alcohol consumption (33.1%, 675/2263) were the predominant acute precipitants. The etiologies of ACLF and types of acute precipitants showed significant regional variation. The pooled 28‐day mortality rate among patients with ACLF was 38.6% (1200/3225, 95% confidence interval [CI] 31.5%–45.8%), and the 90‐day mortality rate was 45.8% (1625/3565, 95% CI 40.3%–51.4%). Temporal analyses demonstrated a decline in virus‐related ACLF, from 42.4% (1012/1761) in the pre‐2014 period to 28.2% (490/1169) post‐2014, and an increase in ALD‐related ACLF, from 31.7% (439/1761) to 48.2% (469/1169). Conclusion The number of patients with ACLF and compensated liver disease remained high, with no improvement over time. The rising prevalence of ALD‐related ACLF over the past decade underscores the need for effective therapies for ACLF and preventive strategies for patients with ALD who are at high risk for ACLF. Trial Registration: https://www.crd.york.ac.uk/PROSPERO ; PROSPERO under the title “ Epidemiological Characteristics of Acute‑on‑Chronic Liver Failure ”. ID: CRD42024366018