An international study published in the Journal of Hepatology provides the first global prospective evidence on liver transplant outcomes in patients with severe acute-on-chronic liver failure (ACLF). The research shows a substantial survival benefit for transplanted patients and identifies a higher risk of post-transplant mortality in patients with five or six organ failures.
The work is part of the CHANCE study, an international project promoted by the European Foundation for the Study of Chronic Liver Failure (EF CLIF), with the support of the European Society for Organ Transplantation (ESOT) and the International Liver Transplantation Society (ILTS). The study aims to identify which patients with severe ACLF may benefit from liver transplantation and which factors are associated with outcomes after transplantation. Dr. Javier Fernández, Head of the Liver Intensive Care Unit at Hospital Clínic Barcelona, researcher in the IDIBAPS group on Chronic Liver Diseases: Molecular Mechanisms and Clinical Consequences, and Head of Clinical Operations at EF CLIF, served as Co-Principal Investigator of the study.
A severe complication of cirrhosis
Acute-on-chronic liver failure is a life-threatening complication that occurs in patients with cirrhosis and is characterized by sudden deterioration and failure of one or more organ systems. Its most severe forms, ACLF-2 and ACLF-3, are associated with very high short-term mortality, while the role and limits of liver transplantation in these patients have long been debated.
To better understand the role of liver transplant in these patients, the CHANCE study prospectively followed 995 patients treated at 63 liver transplant centres across Asia, Europe, Latin America and North America between 2021 and 2023. Among them, 612 underwent liver transplant, while 144 patients with ACLF-2 or ACLF-3 who were not accepted for transplantation were followed for one year.
Liver transplantation improves survival
Patients with ACLF-2 or ACLF-3 who did not undergo transplantation had one-year mortality rates of 73% and 88%, respectively. Among transplanted patients, one-year mortality was 10.5% for ACLF-2 and 20.7% for ACLF-3. In patients with ACLF-2, this rate was similar to that observed in transplanted patients without ACLF (9%).
“For many years, ACLF has been considered a contraindication for liver transplantation. The complexity of managing these patients in intensive care units and the unfavourable outcomes observed in early local series contributed to reinforcing this negative perception,” explains Dr. Javier Fernández. “Previous single-centre studies and registry-based studies suggested a significant improvement in survival among patients with ACLF undergoing liver transplantation. As the largest prospective investigation conducted to date in this field, the CHANCE study confirms these positive results on a global scale and allows their generalisation,” he adds.
The number and type of organ failures determine post-transplant risk
In addition to confirming the benefit of liver transplant in patients with severe ACLF, the study provides information on factors associated with prognosis after transplantation.
Among transplanted patients, one-year mortality increased progressively with the number of organ failures present at the time of transplantation. Mortality was 8.3% in patients without organ failure, 9.6% with one organ failure, 10.5% with two, 14.9% with three and 17.9% with four. In patients with five or six organ failures, mortality reached 41.7%.
The analysis also showed that certain types of organ failure were associated with higher post-transplant mortality, particularly neurological, respiratory and circulatory failure.
According to the authors, these findings support a more individualised assessment of patients with the most severe forms of ACLF, based on the number and type of failing organs rather than solely on disease grade.
Information to support clinical decision-making
The results provide evidence that may help transplant teams assess patients with ACLF-2 and ACLF-3 and identify those most likely to benefit from liver transplant.
The study also found that patients with ACLF-2 or ACLF-3 on the transplant waiting list had almost twice the risk of death or removal from the list due to clinical deterioration compared with patients without severe ACLF, despite having shorter waiting times.
The authors emphasise that these findings should not be interpreted as support for liver transplant in every patient with severe ACLF. The poorer outcomes observed in patients with five or six organ failures highlight the importance of carefully weighing potential benefits and risks in the most severe cases.
An international infrastructure for future research
In addition to its clinical implications, the CHANCE study has established an international infrastructure for the prospective collection of data and biological samples. The project brought together 63 liver transplant centres working with harmonised procedures and collected clinical information together with blood, plasma, urine and DNA samples.
The dataset and biobank generated by the study will provide a platform for future research into ACLF and patients’ response to liver transplantation.
Study reference:
Gustot T, Bernal W, Fernández J, et al. Survival outcomes after liver transplantation in acute-on-chronic liver failure: A prospective study. J Hepatol. 2026 Sep 30:S0168-8278(26)02908-9. doi: 10.1016/j.jhep.2026.09.015.
