Emergency Liver Transplant Effective for Severe Acute-on-Chronic Liver Failure

BOSTON — Prioritizing emergency liver transplantation for patients with severe acute-on-chronic liver failure (ACLF) resulted in relatively good survival outcomes, according to a U.K. study presented here.

Among 39 critically ill patients who were able to undergo emergency transplant, survival reached 85% at a median follow-up of 171 days, with a 1-year survival rate of 78%, reported William Bernal, MD, of King’s College Hospital in London.

All nine patients who did not undergo transplant died, with a median survival of 7 days.

“Currently, we have no other effective treatment options in this setting,” Bernal said during a late-breaking abstract session at the American Association for the Study of Liver Diseases annual meeting. “These data confirm that transplantation is a practical and effective intervention for selected patients with ACLF.”

While different definitions and classifications describe ACLF, there is “a reasonable consensus that it represents a severe manifestation of chronic liver disease,” Bernal noted. “It combines clinical deterioration, usually from an acutely decompensated state, with the development of hepatic and extra-hepatic organ system failure, requiring care in a critical care setting, and carries a very high short- and medium-term mortality.”

In the case of patients with grade 3 ACLF — defined as the development of three or more organ failures — 28-day mortality exceeded 75%, he said, adding that there has been no evidence of survival benefit with treatments such as extracorporeal devices or novel medical therapies.

While there are retrospective data supporting the use of liver transplantation for grade 3 ACLF, he noted that “it remains a controversial indication” for several reasons, including:

• High mortality associated with transplantation in this setting compared with standard transplantation
• Difficulty in identifying cases in which transplantation is likely to be beneficial
• A narrow time window for transplantation
• Prolonged post-transplant hospital stays resulting in high resource use
• No prospective data supporting its use

Launched under the auspices of the NHS Blood and Transplant Liver Advisory Group, the prioritized ACLF tier was piloted across seven U.K. liver transplantation centers, with a planned interval from tier registration to transplantation of 3 days.

Patients eligible for inclusion had to have cirrhosis with liver failure displaying jaundice and coagulopathy, organ dysfunction and failure requiring care in an intensive care unit (ICU), and an expected 28-day survival rate less than 50%.

Patients were excluded if they were over 60 years of age, had previous liver transplantation, a comorbidity or alcohol use precluding elective liver transplantation, or frailty.

At the time of this analysis, 48 patients had entered into the ACLF tier (median age 47 years, 54% men), two-thirds of whom were previously registered for transplantation and had deteriorated on the waitlist. The time in the ICU before entering the ACLF tier was a median of 6 days.

Laboratory values showed that these patients had severe liver injury “and were profoundly unwell when looking at their different organ failure scores,” Bernal observed.

Of the 48 patients who entered the ACLF tier, 39 patients underwent transplantation and nine did not. Patients not transplanted tended to have a higher body mass index, longer ACLF tier waits, and higher organ failure scores compared with patients who were transplanted.

Of the 39 who underwent transplantation, there were 33 survivors. Their median length of ICU stay was 14 days, and median length of hospital stay was 35 days.

Most deaths occurred in the immediate post-liver transplant stay, Bernal said, and were associated with longer wait times and more severe multi-organ failures, and were more likely in “de novo” presentations of ACLF.

For example, Bernal pointed out that the survival rate among transplanted patients who were not previously listed for transplantation (de novo presentations of ACLF) was 73% compared with 92% among patients previously listed for transplantation. Of the six patients who did not survive transplantation, four were not previously listed for transplantation, compared with 11 of 33 survivors.

While transplantation for selected patients with ACLF appears to be practical and effective, Bernal concluded, he also acknowledged it is associated with greater use of resources and higher mortality than standard liver transplantation, “but perhaps not excessively so.”

“There is a clear need for optimization of process,” he noted, “particularly in respect to improved case selection with the quantification and understanding of multi-organ failure severity, and why we are seeing worse outcomes in patients who present with de novo ACLF.”

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