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People with severe acute-on-chronic liver failure (ACLF) were more likely to die than those without ACLF while waiting for a liver transplant, despite having similar survival rates if they did get a transplant, according to interim results of the global CHANCE study.

Among patients with ACLF grades 2 or 3 (Group 1), 28% died or were delisted while waiting for a liver transplant compared with 16% of patients with ACLF 0 or 1 and a Model For End Stage Liver Disease (MELD) score >20 (Group 2; P<0.001), reported Rajiv Jalan, MD, of the University College London, at the European Association for the Study of the Liver annual meeting.

Among Group 1, 68% received a liver transplant compared with 79% of Group 2 (P<0.001).

In a group with severe ACLF who were referred for waitlist evaluation but were not listed (Group 3), 85% died, Jalan told attendees. Notably, the main etiology of liver disease in Group 3 was alcohol-associated cirrhosis, compared with 56% and 48% of Groups 1 and 2 (P<0.001). "That probably is a bias in terms of not transplanting this population of patients," Jalan commented.

ACLF is a condition characterized by multiorgan failure and very high risk of death, occurring in patients with cirrhosis who acutely decompensate, Jalan explained. According to , the risk of death at 28 days among patients with ACLF 2 or 3 is between 30-90%.

The interim analysis of the study included outcomes for 823 patients from 66 liver transplant centers across 21 countries in Asia, Europe, Latin America, and North America.

When researchers looked at mortality by ACLF severity according to MELD-sodium (Na) scores, 50% of those with ACLF 2 and 3 with a MELD-Na score of less than 25 died while waiting for a transplant. "This suggests that these patients are disadvantaged on the current waiting list programs," Jalan stated.

Jalan and colleagues also looked at 3-month mortality rates after transplant by ACLF grades at time of transplantation. In Group 1, 9% of patients who received a transplant at 3 months and 7% in Group 2 died. Percentages of those who died at 3 months by ACLF stage were as follows:

• ACLF 3: 14%
• ACLF 2: 7%
• ACLF 1: 4%
• No ACLF: 7%

The risk of death post-transplant even in ACLF grade 2 or 3 was not significantly different (P=0.051) from those who have decompensated cirrhosis, Jalan reported. "In patients with ACLF grade 3, there's a slightly higher risk of death post-liver transplantation, but remember that without transplantation the risk of death of these patients is nearly 70% or 80%," he pointed out.

"Is a 3-month mortality of 15% acceptable in times where we have limited resources of these organs?" asked Heiner Wedemeyer, MD, of Hannover Medical School in Hanover, Germany, during a Q&A session. "If we have enough organs, I would agree, but if we have many, many other patients waiting who would have a much better outcome, I have some problems with that," he said.

"A 15% risk of death at 3 months [post-transplantation] -- which we think is maybe 20% at 1 year -- is absolutely acceptable," Jalan replied. "These patients are waiting very long on the waiting list, which produces situations in which they're in a much worse state than they would be if they had earlier organ allocation. I think that we could be able to reduce the risk of these patients in the future if they had access to organs earlier."

"The challenge is, how do you come up with objective, verifiable indicators that says this is ACLF 1, 2and 3?," commented W. Ray Kim, MD, of Stanford Health Care in California and president of the American Association for the Study of Liver Diseases, in reference to the lack of global agreed upon definitions for ACLF grading. "I'd like to encourage your investigators to work towards some objective parameters that everybody can trust."

"I think this is a fantastic point," Jalan said. "What we need to do is to generate a score, which is numbers-based rather than based upon how physicians see the patient. I think ACLF 3 is pretty clear, ACLF 2 is more difficult because there is a degree of overlap." He added that his group is working on a new scoring system that incorporates hazard ratios and may be superior to the Chronic Liver Failure Consortium (CLIF-C) ACLF score. "I think that we have to make sure that the organs that the patients that we say have ACLF 3 actually have ACLF 3."

Jalan concluded by emphasizing that if the interim results are confirmed in the study's full analysis, "they strongly argue for increasing access to liver transplantation in a possible change in the organ allocation system for this population of patients with very severe ACLF."

Patients were enrolled in the CHANCE study between July 2021 to October 2023. Recruitment for the trial closed after 1,000 patients were enrolled. The interim analysis included 376 patients in Group 1, 313 patients in Group 2, and 134 patients in Group 3. Of these, 236 of Group 1 patients and 265 of Group 2 patients had received transplants.

In terms of demographics, participants in North America were younger, with a mean age of 49, compared with a mean age of 55 in Europe, 57 in Latin America, and 51 in Asia (P<0.001). Comorbidities and MELD scores, ranging from 30 to 35 among countries, were relatively similar across countries, Jalan said.

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