October 10, 2023 CHANCE celebrates the recruitment of its 1000th patient Significant milestone in the first global prospective study analyzing intention-to-treat survival benefit of liver transplantation for patients with severe acute-on-chronic liver failure (ACLF) – a syndrome characterized by acute decompensation of cirrhosis associated with multisystem organ failure and high short-term mortality.

BARCELONA—The CHANCE Management Team announces the recruitment of patient no. 1000. This new milestone means that the study will progress to a data cleaning stage and primary endpoints will be analyzed. The CHANCE study aims to describe the clinical trajectories of patients with acute decompensation of cirrhosis and ACLF in the liver transplant waiting list, and is expected to contribute to issue new guidelines for organ allocation as there are currently no specific priority criteria for patients with ACLF.

Since its launch in late 2020, 67 centers in 21 countries across the world have joined the CHANCE study with 63 sites actively recruiting patients admitted to hospital for acute decompensation of cirrhosis and referred for a liver transplant evaluation. In this observational study, pre-defined populations of patients that meet the inclusion criteria are grouped based on presentation and severity of ACLF: group 1 includes patients listed for liver transplantation with ACLF grades 2 and 3 at the time of listing or developing ACLF grades 2 or 3 while on the waiting list; group 2 includes patients listed for liver transplantation without ACLF or ACLF grade 1 and poor liver function (this is, with model of end-stage liver disease (MELD) score of more than 20 at the time of listing), and group 3 includes patients with ACLF grades 2 and 3 that are not listed and, thus, do not receive a liver transplant. Exclusion criteria include listing for transplantation of organs other than liver or combined liver–kidney transplantation, previous liver transplantation, and presence of comorbidities such as hepatopulmonary syndrome or moderate to severe portopulmonary hypertension, among other clinical conditions that could negatively affect patient’s prognosis.

In addition to the primary objective (this is, to compare one-year graft and patient survival after liver transplantation in patients with severe ACLF at the time of liver transplant with patients with decompensated cirrhosis without ACLF and transplant-free survival of patients with severe ACLF not listed for liver transplantation), CHANCE aims to assess the proportion of patients with ACLF who are listed for liver transplantation, evaluate the outcomes of waiting list patients with or without ACLF, define futility criteria, define independent predictive factors of mortality in the waiting list and develop a new prognostic model.

To date, more than 1000 patients have been recruited in the CHANCE study, with the majority of patients enrolled in group 1 (this is, patients with severe ACLF listed for liver transplantation). Although Europe is the region that has recruited more patients so far, USA leads the recruitment dashboard followed by Argentina, Brazil and India.

Remarkable milestone

On 5 October 2023, the team led by Prof. Alberto Farias at Hospital das Clínicas in Brazil recruited the 1000th patient. This is a fantastic achievement for all collaborators in CHANCE. Thanks to all the study participants, CHANCE will provide a better understanding of the pathophysiology, clinical trajectory and management of ACLF that will ultimately help to develop equitable, evidence-based guidelines on organ allocation and selection of patients for liver transplantation.

Thierry Gustot, CHANCE Principal Investigator at CUB Erasme Hôpital, Belgium, said: “The enrolment of the 1000th patient reflects the hard work and commitment of many clinicians and professionals whose common goal is to improve survival and quality of life of patients with ACLF. Congratulations to all and especially to Professor Alberto Farias and his team.”

The CHANCE study is promoted by EF CLIF. This study counts with the support of the International Liver Transplantation Society (ILTS), the European Liver and Intestine Transplant Association (ELITA), and the European Association for the Study of the Liver (EASL).

About the CHANCE study

CHANCE is a multicenter, global, observational study designed to assess the benefit of liver transplantation in patients with acute-on-chronic liver failure (ACLF) grade 2 or grade 3. The primary objective of the CHANCE study is to compare 1-year graft and patient survival rates after liver transplantation in patients with ACLF grade 2 or grade 3 at the time of liver transplantation with patients with decompensation of cirrhosis without ACLF-2 or 3 and transplant-free survival of patients with ACLF-2 or 3 not listed for liver transplantation. The international nature of this study will allow for deep assessments of the potential impact of different precipitating factors of ACLF, different types of liver transplantation (deceased donor vs. living donor liver transplantation) and different regional and national allocation systems on transplant outcomes. Besides these clinical objectives, the CHANCE study aims to build a repository of biological samples to explore new biomarkers to predict prognosis on the waiting list and after liver transplantation, and mechanisms of liver and extrahepatic organ recovery.

ClinicalTrials.gov Identifier: NCT04613921