A major international study involving the Royal Free Hospital has added new evidence to a difficult question in liver care: when can a transplant offer a realistic chance of survival to someone whose chronic liver disease has suddenly become critical? The findings suggest that many carefully selected patients with severe acute-on-chronic liver failure may benefit, while also setting out a clear warning for those with the greatest number of failing organs.
Why this group has been difficult to treat
Acute-on-chronic liver failure occurs when a person with cirrhosis or other longstanding liver disease deteriorates rapidly and develops failure in one or more organs. The more severe forms, known as ACLF-2 and ACLF-3, carry a high short-term risk of death. Yet the scarcity of donor organs means transplant teams must judge not only urgency, but whether an operation is likely to help.
That tension has often led to very ill patients being considered too high risk for transplantation. The new research does not remove the need for careful selection. Instead, it provides prospective evidence that the diagnosis grade alone is not a sufficient guide to a patient’s outlook after surgery.
A four-continent cohort
The CHANCE study followed 995 adults at 63 liver-transplant centres in Asia, Europe, Latin America and North America between 2021 and 2023. The Royal Free Hospital was one of the participating centres. The project was an observational study, meaning treatment decisions were made by local clinical teams rather than assigned at random.
Of the participants, 612 received a transplant. Another 144 people with ACLF-2 or ACLF-3 were not offered transplantation and were followed for a year. Among those declined, 73% of patients with ACLF-2 and 88% of those with ACLF-3 died within that period. In the transplanted group, the reported one-year case-fatality rate without a further transplant was 10.5% for ACLF-2 and 20.7% for ACLF-3.
These figures describe outcomes in the study groups; they do not prove that transplantation alone caused the difference. People selected for surgery may have differed from those turned down in ways that cannot be fully captured in an observational comparison. Even so, the scale and prospective design of the cohort give transplant teams more evidence than was previously available from small series and retrospective registries.
Number and type of organ failures matter
The most useful clinical message may be the pattern within the transplant group. One-year case-fatality rose as the number of organ failures present at surgery increased: from 8.3% with none to 17.9% with four. For patients with five or six organ failures, it reached 41.7%. Brain, respiratory and circulatory failure were also linked with higher post-transplant mortality.
This does not create an automatic cut-off. The group with five or six organ failures was small, and the researchers say decisions for the sickest patients should remain individual. It does, however, support looking at the number and nature of organ failures alongside the ACLF grade, rather than treating every severe case as the same.
Pressure before an organ becomes available
The study also underlines how quickly the situation can worsen while a patient waits. Participants with ACLF-2 or ACLF-3 who were on a transplant waiting list had a 27% risk of death or removal from the list because of clinical deterioration, compared with 15% among patients without severe ACLF, despite shorter waiting times.
For London’s specialist liver services, the findings offer a stronger basis for rapid assessment and discussion between intensive-care, hepatology and transplant teams. They do not mean that every patient with severe liver failure will be suitable for a transplant, nor do they change the finite supply of donor organs. But they indicate that selected people previously viewed as too unwell may deserve a more individualised consideration of the potential benefit.
