Conference Coverage

Significant Benefit with Liver Transplantation in ACLF: CHANCE Study


 

FROM EASL 2024

Liver transplantation improves survival in patients with acute-on-chronic liver failure (ACLF), according to interim clinical outcomes of the large, international CHANCE study.

To date, the results show that 3-month post–liver transplantation mortality rates in patients with ACLF grades 2 and 3 were only 9%, which is not significantly different than that of patients with decompensated cirrhosis, with a mortality of 7%.

professor of hepatology, University College London Hospitals, London, England University College London Hospitals

Dr. Rajiv Jalan

“Treatment of ACLF is an unmet medical need,” said Rajiv Jalan, MD, professor of hepatology and honorary consultant in hepatology, University College London Hospitals, London, England.

These findings highlight “the inadequacy of current transplant allocation criteria for patients with ACLF 2 and 3,” which is leading to excess mortality on the wait list, he added.

Dr. Jalan presented the interim results at the European Association for the Study of the Liver (EASL) Congress 2024.

If confirmed in the full analysis, these results argue strongly for increasing access to liver transplantation and changing organ allocation for patients with ACLF 2 and 3, he said.

Organ Allocation Principally Based on MELD Scores

ACLF, which occurs in patients with cirrhosis and acutely decompensated liver disease admitted to hospital, carries a high, short-term risk for death. The risk for 28-day mortality for ACLF 2 and 3 is between 30% and 90% and characterized by multiorgan failure.

As seen in previous data, even patients on the transplant waiting list with a low Model for End-Stage Liver Disease (MELD) score have a risk for death between 20% and 30% if they are ACLF 2 and 3, Dr. Jalan said.

MELD scores do not consider the risk for death because of failure of extrahepatic organs, he added. Existing worldwide organ allocation systems are principally based on patient MELD scores or its variations; therefore, many patients die on the waiting list.

With this in mind, the CHANCE study aimed to compare 1-year graft and patient survival rates after liver transplantation in patients with ACLF 2 or 3 at the time of transplantation with patients with decompensated cirrhosis without ACLF and transplantation-free survival of patients with ACLF 2 or 3 not listed for liver transplantation.

The multicenter observational study comprised 66 liver transplant centers from 21 countries and over 500 investigators. Recruitment was closed after 1000 patients were enrolled.

Patients were aged 54-56 years, 31%-35% were women, 48%-70% had alcohol-related cirrhosis, and 19%-24% had metabolic dysfunction–associated steatohepatitis. MELD scores ranged from 25 to 36.

For the interim results, Dr. Jalan and colleagues assessed mortality on the waiting list and 3-month post–liver transplantation mortality.

Secondary endpoints included quality of life and cost of care.

Of the 823 patients in the study, they were grouped as follows: 376 patients with ACLF 2 or 3 listed for liver transplantation (group 1), 313 patients with ACLF 0 or 1 and MELD score > 20 listed for liver transplantation (group 2), and 134 patients with ACLF 2 or 3 not listed for liver transplantation (group 3).

Overall, patients in group 1 had very severe ACLF; 177 patients with ACLF 3 had three or more organ failures, Dr. Jalan noted.

“It is interesting to note that, in group 3, there is an overrepresentation of alcohol-related cirrhosis, and this might reflect a bias in transplantation,” he added.

Dr. Jalan highlighted geographical points of difference. Patients in the United States were younger, which could be important when interpreting results of post-transplantation outcomes. In Asia, the majority of the patients were men and primarily from India, where living donor transplantation is commonly performed. In Latin America, only 33% of study participants had alcohol-related cirrhosis in contrast to 67% of those in North America.

However, “comorbidities across the world were similar, and MELD scores were also similar,” Dr. Jalan said.

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