Harmonizing the definition of acute-on-chronic liver failure: Key outcomes from a global consensus meeting

Leading international experts gathered ahead of EASL 2026 to advance efforts toward a unified global definition of ACLF, with major implications for future research, clinical trials, and patient care worldwide.

Acute-on-chronic liver failure (ACLF) is a severe syndrome in patients with chronic liver disease, marked by acute decompensation and multi-organ failure. Despite its clinical importance, there is no single universally accepted definition, with regional differences in diagnostic criteria and classification. This lack of consensus has limited the comparability of research, the design of clinical trials, and the standardisation of care.

The Global ACLF Consensus Meeting, which took place the day before EASL Congress 2026, was convened to address these inconsistencies and support the development of a unified international definition to advance research and clinical practice.

In this interview, EASL Secretary General Prof. Debbie Shawcross outlines the existing discrepancies in the definition of ACLF, the importance of a standardized definition globally, and the potential impacts on future care and research. Prof. Shawcross also explores the first outcomes of the international collaboration, what was discussed at the consensus meeting, and the next steps in unifying the global definition.

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Could you outline the existing global discrepancies in the definition of ACLF?

The concept of ACLF, or acute-on-chronic liver failure, was first coined about 25 years ago. In fact, we were reflecting yesterday on the first meeting in Boston in 2002, when the idea of a patient with advanced liver disease deteriorating and developing organ dysfunction and failure was recognized and described as ACLF. Before then, this syndrome wasn’t really recognized.

Over the past 25 years, progress has been very limited, mainly because people have taken different regional or continental approaches to the topic. In Europe, for example, ACLF has been defined through the EASL-CLIF Consortium, while in India, they have done the same through AARC. The challenge is that these definitions and datasets are driven by the regional population. As a result, it has been difficult to combine data globally and arrive at a single, unified understanding of ACLF.

Another example, is that datasets from China or India are often focused on patient populations where hepatitis B is a major cause or precipitating factor for ACLF. In contrast, in Europe, alcohol-related liver disease and metabolic liver disease are more prominent, while in the United States, metabolic dysfunction-associated liver disease is now probably the leading cause.

Why is standardizing the definition of ACLF important and what are the potential impacts on future care and research?

Our goal is to develop a definition of ACLF that is applicable worldwide. Standardization is essential because, up to now, we have relied on regional datasets and definitions. This is important because often data is collected from leading centers and does not fully reflect what access patients have in other parts of the world, for example, in rural and urban areas. Furthermore, more than 80% of the global population does not have access to intensive care. We therefore need to simplify the concept and create a definition that is applicable to everyone around the world, so that we can improve outcomes for patients.

At the moment, we are effectively trying to compare apples, oranges, and pears. The differences between populations make it difficult to align findings directly. However, there are many common features across all of these datasets, and our aim is to identify and unify those shared elements into a definition that is both clinically meaningful and easy to understand.

What first outcomes of this international collaboration were presented?

We presented outcomes from several working groups that have been busy over the last few months looking at different aspects. We had working groups looking at: the definition of ACLF, the role of transplantation, the role of intensive care (where available), alcohol- and virus-related disease, drug therapies, and clinical trial endpoints and development.

The working groups met regularly over the last few months and developed several statements representing areas of agreement. They conducted a Delphi process among working group members to identify where consensus existed and where opinions differed.

The purpose yesterday was to present those statements to a wider audience and gather their opinions. We wanted to know whether people agreed, where they disagreed, and how the proposals could be improved.

Importantly, we had participation from 299 individuals representing five continents, which gave us a genuinely global perspective. There were different viewpoints and contentious issues discussed, but that really was the purpose of the meeting.

What is great about this initiative is that all our sister societies have signed up to it – the AASLD, ALEH, APASL, and SOLDA. The outputs will be published across all the societies’ journals, which further reinforces the international nature of the collaboration.

What further points were discussed at the consensus meeting?

At our harmonization meeting, we heard from Shirin Hemmat at the FDA, who discussed how regulators look at drug and therapy development. One of the major challenges in ACLF is that we still do not have any licensed, effective therapies. Many treatments have entered early-stage trials, but numerous candidates have failed along the way.

What was encouraging was hearing how regulators view where we need to go. It is important not only to establish simple, shared definitions, but also to ensure that it is described in a way that is meaningful for patients and clear.

In the past, regulators tended to focus on very clear-cut endpoints, such as whether a therapy increased survival or reduced the need for transplantation. Nowadays, it is increasingly important to look at patient-related outcomes and health span is becoming more important than lifespan in terms of quality of life.

In addition, we heard keynote lectures from two individuals in the field who have been involved from the start. They provided an overall perspective on our progress over the last 25 years and the work still to be done.

What will be the next steps in unifying the global definition?

The next steps will be to refine the statements, conduct another Delphi round, and ultimately publish the consensus document. In terms of timelines, we are planning a follow-up meeting at The Liver Meeting® in Denver in November, where we will review progress on the consensus document and work toward finalizing it.

One particularly important aspect of this initiative is that it is being published by the societies, rather than individuals. One of the problems in the past is that ACLF publications have been by individuals, who sometimes have competing interests or perspectives. By publishing a unified consensus through the societies themselves, this initiative will be truly independent and hopefully far more widely accepted.