Clinical Course of acute-on-chronic liver failure syndrome and effects on prognosis.

BACKGROUNDS: Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation of cirrhosis, organ failure(s) and high 28-day mortality. We investigated whether assessments of patients at specific time points predicted their need for liver transplantation (LT), or the potential futility of their care. METHODS: We assessed clinical courses of 388 patients who had ACLF at enrollment, from February through September 2011, or during early (28-day) follow-up of the prospective multicenter European Chronic Liver Failure (CLIF) ACLF in Cirrhosis (CANONIC) study. We assessed ACLF grades at different time points to define disease resolution, improvement, worsening, or steady or fluctuating course. RESULTS: ACLF resolved or improved in 49.2%, had a steady or fluctuating course in 30.4% and worsened in 20.4%. The 28-day transplant-free mortality was low-moderate (6-18%) in patients with non-severe early course (final no ACLF or ACLF-1) and high-very high (42-92%) in patients with severe early course (final ACLF-2 or -3) independently of initial grades. Independent predictors of course severity were CLIF Consortium ACLF score - (CLIF-C ACLFs) and presence of liver failure (total bilirubin ≥ 12 mg/dL) at ACLF diagnosis. Eighty one percent had their final ACLF grade at 1 week, resulting in accurate prediction of short-(28-day) and mid-(90-day)term mortality by ACLF grade at 3-7 days. Among patients that underwent early LT, 75% survived for at least 1 year. Among patients with ≥4 organ failures, or CLIF-C ACLFs >64 at days 3 - 7 days, and did not undergo LT, mortality was 100% by 28 days Conclusions: The assessment of ACLF patients at 3-7 days of the syndrome provides a tool to define the emergency of LT and a rational basis for intensive care discontinuation due to futility. This article is protected by copyright. All rights reserved. KEYWORDS: Organ failures; cirrhosis; futility of care; liver transplantation; prognosis