Acute‐on‐chronic liver failure (ACLF) is characterized by acute decompensation (AD) 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. 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 study. We assessed ACLF grades at different time points to define disease resolution, improvement, worsening, or steady or fluctuating course. 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‐to‐moderate (6%‐18%) in patients with nonsevere early course (final no ACLF or ACLF‐1) and high‐to‐very high (42%‐92%) in those 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‐term (90‐day) 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: 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 owing to futility. (Hepatology 2015;62:243‐252)

Infections ACLF Death Different clinical courses of acutely decompensated cirrhosis Pre-ACLF Unstable decompensated cirrhosis Stable decompensated cirrhosis 0 90 180 270 360 Days Highlights Patients with acutely decompensated cirrhosis without ACLF develop 3 different clinical courses. Patients with pre-ACLF develop ACLF within 90 days and have high systemic inflammation and mortality. Patients with unstable decompensated cirrhosis suffer from complications of severe portal hypertension. Patients with stable decompensated cirrhosis have less frequent complications and lower 1-year mortality risk.

Financial support: The study was supported by the European Foundation for the Study of Chronic Liver Failure (EF-Clif). EF-Clif received unrestricted donations from Grifols and Cellex Foundations and is partner or contributor in several projects of the EU Horizon 2020 research program. Maria Papp was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Science (BO/00232/17/5) and the New National Excellence Program of the Ministry of Human Capacities (ÚNKP-18-4 Bolyai Plus). Pere Ginès is a recipient of the ICREA ACADEMIA AWARD (2015-2020). Disclosures The EASL-CLIF Consortium is a network of 101 European University hospitals supported by the EF-Clif. EF-Clif is a private non-profit organization aimed at improving clinical and translational research in cirrhosis. The scientific agenda of the EASL-CLIF Consortium and the specific research protocols are made exclusively by the Steering Committee members without any participation of pharmaceutical companies.

No abstract

No abstract

No abstract

Acute-on-chronic liver failure (ACLF) AVB + ACLF High rebleeding rate (25.2%) in 42 days High mortality rate (51.0%) in 42 days Pre-emptive TIPS in AVB + ACLF Low rebleeding rate (4.5%) in 42 days Low mortality rate (13.6%) in 42 days Pre-emptive TIPS Acute Variceal Bleeding (AVB) Highlights Variceal bleeding is frequently associated with ACLF in cirrhosis. ACLF is independently associated with rebleeding and mortality. Patients with variceal bleeding and ACLF can benefit from a preemptive (early) TIPS.

Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF.