As the CHANCE study approaches its first publication milestone, members of the leadership and coordination teams reflected on its clinical relevance, unique design, and future impact.

Bringing global prospective data into focus, the study is expected to guide fairer transplant access and improve outcomes in critically ill ACLF patients.

“Patients with ACLF, particularly those with severe forms (ACLF-2 or -3), have a dramatic short-term mortality rate with no currently accepted life-saving treatment. ACLF remains a controversial indication for liver transplantation, but some retrospective reports suggest adequate post-transplantation outcomes. By its prospective and global design nature, the CHANCE study represents a unique opportunity to objectively assess access to liver transplantation and post-transplant outcomes in these patients. We collected detailed data in expert centers worldwide on transplant candidates with severe ACLF—their outcomes on the waiting list, donor characteristics, surgical and post-operative details. Based on this information, we aim to propose objective listing criteria, an adequate allocation system, and clinical criteria for recipients and donors to ensure acceptable outcomes after liver transplant”, said Thierry Gustot.

Designed to support complex transplant decisions in real time, the data may offer a practical tool for critical care teams. “Being able to correctly assess whether people who are critically ill with ACLF are candidates to undergo emergency liver transplantation is key to ensuring that the transplant is successful. The data we get from the CHANCE study will make it possible to do this—providing a unique opportunity to understand the features that identify whether a patient is well enough—or too sick—to undergo surgery. We will provide clinicians with an evidence base and framework to help them make what are often extremely difficult clinical decisions”, explained William Bernal.

Building on the foundation laid by previous EF CLIF studies, the findings reaffirm and expand early hypotheses. Javier Fernández, who also serves as Head of Clinical Operations at EF CLIF, said: “The CANONIC and PREDICT studies were pivotal in defining ACLF and identifying its precipitants, risk factors, and pathogenic pathways. CANONIC also suggested that salvage liver transplantation should be performed in selected patients with severe forms of ACLF. The CHANCE study confirms this idea and demonstrates that liver transplantation is not only feasible but associated with good prognosis in these critically ill patients. This important finding opens a window of opportunity—a chance—for extremely severe patients who currently are not considered for liver transplantation in many centers around the world.”

Final analyses are underway, with the first manuscripts expected within the next few months. “The CHANCE study was conceptualized and started after a series of retrospective and registry studies, with a view to collecting relevant prospective data to explore and determine the role of liver transplantation for patients with ACLF. The data is extremely rich and of high quality, thanks to the efforts of all the investigators. The initial results clearly provide evidence of the benefit of liver transplantation and the need for prioritization of patients with advanced ACLF. We are in the final stages of data analysis and will be submitting a series of papers, starting with the first one in about three months. We welcome input from CHANCE investigators and are convinced that the hepatology community will benefit, as these peer-reviewed publications will provide the data needed to change clinical practice in their respective countries”, explained Rajiv Jalan.

Ensuring data quality across a global, multidisciplinary study like CHANCE requires careful coordination. The data management team is focused on maintaining data completeness and consistency across participating hospitals. “One of the biggest challenges has been understanding the different ways each center and country work—what applies in North America may not be the same in Europe, Asia, or Latin America. Because CHANCE is a long-term study, we’ve also had to adjust to changes in both local and central teams over time. Another layer of complexity comes from the variety of professionals involved—not just hepatologists, but also surgeons and intensivists—who tend to enter data based on their specific clinical priorities. Our job is to harmonize this input and ensure the same level of detail across the entire case report form. We do this by running regular quality checks, including on sections that were already reviewed, so the dataset remains accurate and complete”, said Cristina Sánchez-Garrido.

Centering on key survival comparisons, the first analyses and modeling approaches have now been outlined. Eva Usón explained: “The first abstract of CHANCE focuses on the main objective: to compare 1-year graft and patient survival rates after liver transplantation in patients with ACLF-2 or -3 at the time of liver transplant, with those of patients with decompensated cirrhosis without ACLF-2 or -3, and with transplant-free survival of patients with ACLF-2 or -3 not listed for liver transplantation. In addition to survival comparisons, we are analyzing multivariate models to identify factors associated with mortality.”

At site level, integrating clinical nuance with data standards has proven key to the study’s strength. “From a clinical and data integration perspective, the most rewarding part has been contributing to the transformation of locally generated information into high-quality multicenter evidence. CHANCE is an ambitious study, and one of the main challenges has been harmonizing diverse clinical practices and data structures across sites. As a hepatologist with a strong focus on clinical research, I particularly value the role of local teams—not only in ensuring data quality and consistency, but also in providing clinical insight that will enhance the interpretation and impact of the first publication”, said Juan Manuel Díaz.