Grade 1 Acute on Chronic Liver Failure Is a Predictor for Subsequent Grade 3 Failure

Background and Aims Acute on chronic liver failure (ACLF) results in extremely high short-term mortality in patients with underlying cirrhosis. The European Association for the Study of the Liver criteria grade ACLF severity from 1 (least severe) to 3 (most severe) based on organ failures (OFs) that develop after an acute decompensation (AD). However, the implications of surviving low-grade ACLF in terms of risk of subsequent high-grade ACLF are unclear. Approach and Results We conducted a retrospective cohort study of patients with compensated cirrhosis in the Veterans Health Administration database from January 2008 to June 2016. Propensity matching for grade 1 (G1) ACLF, followed by Cox regression, was used to model risk of subsequent grade 3 (G3) ACLF. Stratified analyses of different ADs and OFs were also performed. We identified 4,878 patients with well-matched propensity scores. G1 ACLF events conferred a significantly increased risk of subsequent G3 ACLF relative no previous G1 ACLF (hazard ratio, 8.69; P < 0.001). When stratified by AD, patients with ascites or hepatic encephalopathy were significantly more likely to develop G3 ACLF relative to those with gastrointestinal bleed or infection as an AD (P < 0.001). Risk of G3 ACLF also varied significantly by type of OF characterizing previous G1 ACLF, with liver, coagulation, and circulatory failure posing the highest increased risk. Conclusions Patients who recover from G1 ACLF have substantially increased risk of later developing G3 ACLF as compared to those who never have G1 ACLF. Moreover, reversible decompensations for G1 ACLF have a lower risk of G3 ACLF, and liver-intrinsic OFs confer a much higher risk of G3 ACLF. These findings have implications for prognosis, future surveillance, and triaging early transplant evaluation.