Transplant waitlist mortality or removal was highest among patients who had acute or chronic liver failure plus at least three extra-hepatic organ failures (ACLF-3) – regardless of model for end-stage liver disease (MELD) score, an analysis of the United Network for Organ Sharing (UNOS) database found.
The study revealed a 43.8% mortality or removal rate at 28 days after listing, suggesting the need for giving these patients a higher priority for transplant. Nearly 44% of patients with ACLF-3 with a MELD score less than 25 will die or be removed within 28 days of listing, wrote Vinay Sundaram, MD, MSc, of Cedars-Sinai Medical Center in Los Angeles, and colleagues in Gastroenterology.
“So, certain patients with ACLF-3 have poor outcomes regardless of MELD-Na score,” Sundaram told MedPage Today. “Many of these patients will have significantly improved survival if they undergo liver transplant, particularly if performed early after listing,” he added, calling for additional research into the prioritization of patients with severe ACLF on waiting lists.
Liver transplantation within 30 days of listing dramatically improved post-transplant survival, the study found, while the need for mechanical ventilation, an indicator of respiratory failure during transplantation, was strongly associated with reduced post-transplant survival, the researchers found.
In terms of 1-year post-transplant survival, the following variables were independent predictors:
- Mechanical ventilation at liver transplantation: HR 1.49 (95% CI 1.22-1.84)
- Donor risk index above 1.7: HR 1.22 (95% CI 1.09-1.35)
- Transplantation within 30 days of listing: HR 0.89 (95% CI 0.81-0.98)
The timing of transplantation for ACLF patients has been controversial, Sundaram and associates noted. To clarify this issue, they studied adult patients in the UNOS registry listed for transplantation from 2005 to 2016, excluding any with acute or fulminant liver failure or hepatocellular carcinoma.
A total of 50,552 patients met inclusion criteria at the time of transplantation, of which 57.9% had no ACLF, 14.6% had ACLF-1, 14.9% had ACLF-2, and 12.6% had ACLF-3. Mean age was about 52 and about 62% were male.
The ACLF-1 group was the oldest and had the highest proportion of males, while those without ACLF had the highest proportion of Caucasians. Body mass index was similar across all patient categories. In terms of etiology, ACLF-2 had the greatest percentage of alcoholic liver disease, while the no-ACLF group had a larger proportion of hepatitis C infection.
ACLF-3 patients had the smallest proportion of males (62.8%), the smallest percentage of Caucasians (65.9%), and the greatest proportion of Hispanics (19.1%). The percentage of patients with alcoholic liver disease was highest among ACLF-2 (35.1%) and patients with ACLF-3 (34.9%), while HCV-induced cirrhosis was lowest in these patient groups.
Mean MELD-Sodium (Na) score at transplantation was significantly greater among patients with ACLF-3, at 37.4. Among the patients with ACLF-3, 56% had three-organ failure alone, whereas 26% had four-organ failure, 14% had five-organ failure, and 5% had six-organ failure.
In terms of donors, ACLF-3 patients received organs from younger donors (mean age 38.7 years), fewer organs from diabetic donors (8.8%), more organs from donors dying of head trauma (38.0%), and the smallest percentage of organs from high-risk donors with a donor risk index of 1.7 or more (22.9%).
One-year survival after transplant was lowest among patients with ACLF-3 (81.8%) vs other groups (88.1%-91.9%, P<0.001). Those who survived for 1 year had a lower prevalence of mechanical ventilation use (33.1% vs 49.0%, P<0.001) and circulatory failure (49.8% vs 60.6%, P<0.001).
The authors cited a recent registry analysis revealing a 1-year post-transplant survival of greater than 80% for patients with ACLF-3 who received early transplants within 30 days of waitlist registration. “Despite the limitations, these findings suggest transplantation for ACLF-3 may not be an ‘exercise in futility,'” Sundaram and associates wrote. “However, given the limited availability of donor organs, the benefit of transplantation in ACLF-3 must also be balanced against the risk of poor post-transplant outcomes.”
The authors called for additional research on the timing of liver transplantation for patients with ACLF-3.
They acknowledged several limitations to their retrospective analysis, including the potential for misclassification at listing and transplant in a large public database and the lack of data on infection rates. Moreover, the study’s a priori identification of clinically significant variables may have introduced bias, potentially leading to the observation of associations that did not exist or the failure to observe associations that did exist.
Another limitation was its focus on 1-year rather than longer-term survival. In addition, the indications for mechanical ventilation were not provided in the database and some usage may not have been for respiratory failure. Some patients with lung injury and respiratory failure may not have undergone intubation at the time of transplant.
This study received no grant support. One co-author reported research collaborations with Takeda and Yaqrit, of which he is the founder, and he is the inventor of a patented device licensed to Mallinckrodt Pharma.