Biomarker discovery

CHANCE: Liver transplantation in patients with cirrhosis and severe acute-on-chronic liver failure – Indications and outcomes

The issue

Acute-on-chronic liver failure (ACLF) is a life-threatening condition without evidence-based treatment. The role of liver transplantation is still incompletely understood. A few retrospective studies suggest that it is associated with a substantial survival benefit. We do not currently know the criteria for selecting candidates, the risk factors for post-transplant mortality and the most appropriate way to position these patients on the waiting list. Some studies also suggest that liver transplantation of patients with ACLF-2 or -3 is associated with significant resource mobilization, longer hospitalizations and more frequent complications. In a context of organ shortage, we must ensure equitable distribution of livers to recipients to ensure adequate overall outcomes.

The approach

CHANCE is a multicenter, global, observational study designed to assess the benefit of liver transplantation in patients with ACLF grade 2 or grade 3. This study counts with the support of the International Liver Transplantation Society (ILTS) and the European Liver and Intestine Transplant Association (ELITA) to recruit 2000 patients in 80 centers in 27 countries around the world. 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 (e.g., alcohol vs. hepatitis B virus flare), different types of liver transplantation (deceased donor vs. living donor liver transplantation) and different regional and national allocation systems on transplant outcomes. Beside 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.

The CHANCE study will be the first prospective study analyzing intention-to-treat liver transplantation for patients with ACLF-2 or -3. The description of the clinical trajectories on the waiting list could allow us to define potentially new rules for organ allocation. Demonstrating the risk factors for post-transplant mortality could be the basis for defining transplant limits. These results will be essential to select the optimal candidates for transplantation and to define which procedure and which organ (deceased donor and living donor, extended donor criteria) are acceptable in this specific situation.

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