Until now, there has been no global agreement on how organ system failures should be defined in cirrhosis. Different hospitals and research groups used different criteria, making it difficult to compare outcomes or design effective treatments.

An international panel of hepatologists and intensivists now agrees on standardized definitions of organ system failures in patients with cirrhosis. Published in Gastroenterology, the consensus statements aim to harmonize how ACLF is identified and treated worldwide, ensuring that patients at the highest risk are recognized earlier, and that future studies and clinical trials build on the same scientific foundation. 

Their statements cover how to define failure of major organ systems (namely the liver, kidney, brain, coagulation, digestion, circulation, and respiration), and major precipitants of hepatic and extrahepatic organ failure (this is, infections and immune dysfunction) in patients with cirrhosis. The consensus goes one step further by shaping how ACLF itself should be defined. According to the experts, ACLF is present when a person with cirrhosis develops clear signs of organ failure — such as severe jaundice and blood clotting problems (liver failure), confusion linked to brain dysfunction, kidney injury, low blood pressure, breathing difficulties, or an inability to take in enough nutrition. By setting these criteria, the document creates a common medical language that clinicians and researchers worldwide can use to recognize ACLF in the same way. 

“There are currently different diagnostic criteria for organ system failures across continents; these differences creating uncertainties regarding criteria for organ failures that should be used for designing international interventional trials of therapies against mechanisms underpinning ACLF. It was therefore important to determine diagnostic criteria that received the agreement of investigators from different parts of the world” said Richard Moreau, Director of EF CLIF and senior co-author of the consensus paper.

The consensus underlines:

• Consistency with intensive care standards so that liver patients can be managed in line with broader critical care practices.
• Clear diagnostic biomarker thresholds (such as specific bilirubin and international normalized ration (INR) values for liver failure, or creatinine changes for kidney injury).
• Recognition of infection and immune dysfunction as central drivers of ACLF.
• Guidance for research so that clinical trials and new drug development use the same entry and end points.

By aligning hepatology with liver critical care, this shared definition is expected to speed up research into how ACLF develops and to harmonize the way the condition is managed in hospitals and studied in clinical trials.

“These consensus statements should be viewed as a promising signal indicating that main stakeholders in this field agreed to engage an harmonization process regarding definitions of organ system failures and consequently ACLF”, concluded Moreau.

Other authors in the consensus paper are Jasmohan S Bajaj, Debbie L Shawcross, Ashok Choudhury, Constantine J Karvellas, Jacqueline G O’Leary, Jonel Trebicka, Anand V Kulkarni, Sebastian Marciano, Sumeet K Asrani, Madhumita Premkumar, Dominique Thabut, Qing Xie, Mark Sonderup, Simone I Strasser, Alberto Queiroz Faria, Mario R Alvares-da-Silva, Aldo Torre, Jennifer C Lai, Qin Ning, Nipun Verma, Sakkarin Chirapongsathorn, Manuel Mendizabal, Sombat Treeprasertsuk, William Bernal, Lisa B VanWagner, Rakhi Maiwall, Salvatore Piano, Agustin Albillos, Guadalupe Garcia-Tsao, Paolo Angeli, K Rajender Reddy, Florence Wong, Shiv K Sarin, and Patrick S Kamath.