A new global multisociety consensus, published simultaneously in Journal of Hepatology, Hepatology, Annals of Hepatology and Hepatology International, brings together the expertise of five international liver societies: the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD), the Asian Pacific Association for the Study of the Liver (APASL), the Latin American Association for the Study of the Liver (ALEH), and the Society on Liver Disease in Africa (SOLDA). The EASL-CLIF Consortium, a research network of EF CLIF, played a pivotal role in this international initiative, making two major contributions to the development of an evidence-based definition and grading system for ACLF.
First, the Consortium used data from 2748 patients with cirrhosis and acute decompensation included in the EF CLIF integrated database. This extensive and well-characterized clinical dataset was instrumental in developing and evaluating the proposed diagnostic criteria and severity grading system. This contribution helped ensure that the new definition and grading system were grounded in robust scientific evidence, reflected the clinical characteristics and prognostic implications of the syndrome, and were supported by a systematic assessment of their ability to identify patients at different levels of disease severity and risk of mortality.
Second, through its well-established international collaborations, the Consortium facilitated the external validation of the new definition and grading system in two large, independent Chinese cohorts: a Ruijin Hospital cohort and a cohort from the First Affiliated Hospital, Zhejiang University School of Medicine. Together, these contributions provided strong, independent validation across geographically distinct patient populations, strengthening the scientific validity and applicability of the new ACLF definition and grading system.
The consensus builds on previous efforts to define ACLF, bringing together regional experience and international evidence to establish a shared framework that can be applied across different healthcare settings. Its aim is not to replace existing regional definitions, but to harmonize them in ways that support clinical practice, research and the development of future therapies.
The harmonization initiative brought together representatives from the five societies, including senior experts and early-career investigators. Working groups reviewed the available evidence and developed proposals, which were then discussed and assessed by the wider group.
A key milestone in this process was an open consensus meeting held in Barcelona on 27 May 2026, ahead of EASL Congress 2026. The proposals were presented and discussed with participants, including questions raised during the meeting. The working groups subsequently revisited and refined several statements, which were assessed again before the final consensus was established.
The Barcelona meeting built on previous consensus work and provided an opportunity to discuss the proposed framework with a broader international audience, contributing to the development of the final recommendations.
One important aspect of the consensus is the definition of liver failure as the primary condition required for an ACLF diagnosis. The framework identifies liver failure using two measures: bilirubin of at least 5 mg/dL and an international normalized ratio (INR) of at least 1.5, measures that help identify severe impairment of liver function.
The consensus also recognizes extrahepatic organ dysfunction together with extrahepatic organ failure. This distinction is important because organs may begin to function abnormally before they progress to outright failure. Recognizing dysfunction at an earlier stage may help clinicians identify patients at risk and consider timely intervention.
“By establishing liver failure as an essential prerequisite for diagnosis and recognizing extrahepatic organ dysfunction and failure as determinants of disease severity, this international consensus represents a major step towards a unified, biologically meaningful definition of ACLF”, said Paolo Angeli, Chair of the EASL-CLIF Consortium Steering Committee and Full Professor of Internal Medicine at University of Padova, Italy. “Importantly, it establishes a common conceptual framework that reconciles previously divergent diagnostic approaches, moving beyond a heterogeneous collection of organ failures towards a shared understanding of the syndrome”.
The implications extend well beyond achieving agreement on terminology. For clinicians, this approach offers clearer criteria for recognizing ACLF, assessing its severity, and identifying patients who may require closer monitoring, escalation of care, or early evaluation for liver transplantation. For researchers, it provides a common diagnostic framework that can improve the comparability of studies, facilitate the selection of more homogeneous patient populations for clinical trials, and support the development of targeted treatments.
“Although its impact will require further validation across diverse populations and healthcare systems, it lays the groundwork for more consistent clinical decisions, better coordinated research, and, ultimately, improved patient outcomes worldwide”, added Angeli.
A shared definition of ACLF is important not only for clinical care, but also for research. When studies use different criteria to identify patients or measure outcomes, their findings can be difficult to compare. A harmonized framework can help researchers describe patient groups more consistently and generate evidence that is more readily assessed across studies and regions.
The consensus further considers how clinical trials should assess whether a treatment is beneficial. Because ACLF can change rapidly and affect several organ systems, evaluating treatment effects requires outcomes that reflect meaningful changes in patients’ condition.
In addition, the consensus discusses the use of standardized clinical-trial endpoints and approaches such as the desirability of outcome ranking (DOOR), which considers several patient outcomes combined rather than relying on a single measure. These approaches may help capture the complex course of ACLF and support the evaluation of future therapies.
European Association for the Study of the Liver (EASL); American Association for the Study of Liver Diseases (AASLD); Asia-Pacific Association for the Study of the Liver (APASL); Latin American Association for the Study of the Liver (ALEH); Society on Liver Disease in Africa (SOLDA). Acute-on-chronic liver failure: A global multisociety consensus on definitions. J Hepatol 2026 Oct 30:S0168-8278(26)02898-9. DOI: 10.1016/j.jhep.2026.09.005. Epub ahead of print.
American Association for the Study of Liver Diseases (AASLD); European Association for the Study of the Liver (EASL); Asia-Pacific Association for the Study of the Liver (APASL); Latin American Association for the Study of the Liver (ALEH); Society on Liver Disease in Africa (SOLDA). Acute-on-chronic liver failure: A global multisociety consensus on definitions. Hepatology 2026 Oct 30. DOI: 10.1097/HEP.0000000000001891. Epub ahead of print.
European Association for the Study of the Liver (EASL); American Association for the Study of Liver Diseases (AASLD); Asia-Pacific Association for the Study of the Liver (APASL); Latin American Association for the Study of the Liver (ALEH); Society on Liver Disease in Africa (SOLDA). Acute-on-chronic liver failure: A global multisociety consensus on definitions. Ann Hepatol 2026 Oct 30:102453. DOI: 10.1016/j.aohep.2026.102453. Epub ahead of print.
European Association for the Study of the Liver (EASL); American Association for the Study of Liver Diseases (AASLD); Asia-Pacific Association for the Study of the Liver (APASL); Latin American Association for the Study of the Liver (ALEH); Society on Liver Disease in Africa (SOLDA). Acute-on-chronic liver failure: A global multisociety consensus on definitions. Hepatol Int 2026 Oct 30. DOI: 10.1007/s12072-026-11169-2. Epub ahead of print.
