Effect of the clinical course of acute-on-chronic liver failure prior to liver transplantation on post-transplant survival

Abstract

Background and aims: Acute on chronic liver failure (ACLF) yields the highest risk of short-term mortality, along the spectrum of cirrhosis. We evaluated whether the rising prevalence of nonalcoholic steatohepatitis (NASH) in the United States is reflected among waitlist registrants with ACLF. Methods: We analyzed the United Network for Organ Sharing (UNOS) registry, years 2005-2017. Patients with ACLF were identified using the EASL-CLIF criteria and categorized into those with NASH, alcoholic liver disease (ALD), and hepatitis C virus (HCV) infection. Statistical analysis included linear regression and Chow's test to determine significance and divergence in trends, and Fine and Grey's competing risks and Cox proportional hazards regression to assess waitlist outcomes. Results: Between 2005 and 2017, waitlist registrants for NASH-ACLF rose 331.6% (p<0.001). ALD-ACLF increased 206.3% (p<0.001), while HCV-ACLF declined 45.2% (p=0.018). This increase in NASH-ACLF occurred across all UNOS regions, rising by 666.7% in region 11. The NASH-ACLF population is aging, and currently 31.5% of the group is age 65 or older. Although NASH-ACLF candidates did not have greater 90-day waitlist mortality (SHR=0.84, 95% CI 0.77-0.92) relative to other etiologies, since 2014, 90-day waitlist mortality has improved for ALD-ACLF (HR=0.78, 95% CI 0.70-0.88) and HCV-ACLF (HR=0.76, 95% CI 0.67-0.85) but not for NASH (HR=0.93, 95% CI 0.81-1.08). Conclusions: NASH is the fastest rising etiology of cirrhosis among transplant registrants with ACLF in the United States. Since 2014, waitlist outcomes have 4 improved for ALD-ACLF and HCV-ACLF, but not for NASH-ACLF. With the aging NASH population, patients with NASH-ACLF may eventually have the highest risk of death on the waiting list.

Editorial: Transplantation in the cirrhotic patient with multiorgan failure: Adding more pieces to an incomplete puzzle

“…Additionally, the current investigation provides data regarding easily testable biomarkers, specifically serum lactate level and leukocyte count, thereby adding additional tools to aid in clinical decision‐making. It also is notable that recipients with a TAM score >2 had a significantly greater prevalence of brain, circulatory, and respiratory failure relative to those with a TAM score <=2, thus supporting findings from a prior study that demonstrated that the presence of brain, circulatory, or respiratory failure at the time of transplantation had a significant association with post‐LT mortality 4 . Finally, the authors demonstrated that the TAM score had greater accuracy in predicting posttransplant mortality compared to other scoring systems such as the balance at risk (BAR) or Chronic Liver Failure Consortium ACLF score.…”

“…First, the use of a binary cutoff for age >=53 requires further examination. Although older age is associated with poorer survival in transplanted ACLF‐3 patients, 4 chronological age alone will not account for frailty or sarcopenia, which may be more important determinants of survival. Second, although the authors studied a large cohort of patients transplanted with ACLF‐3, the TAM score was derived using only 22 patients who met the primary outcome of death within 1 year.…”

Considerations for Prognosis, Goals of Care, and Specialty Palliative Care for Hospitalized Patients With Acute‐on‐Chronic Liver Failure

“…We provided several scenarios when SPCs should be considered and tools to structure family meetings when discussing prognosis of ACLF. Although there are now encouraging data to list severe ACLF patients challenging the "too ill for liver transplantation" paradigm, (5,6,10) it is important to integrate principles of PC early in ACLF for both patient/caregiver comfort. In the lack of established guidelines, future research should assess the effect on wait-list mortality and quality of life in patients with ACLF regardless of listing status.…”

Acute on Chronic Liver Failure: Role of the Bacterial Infections

“…Many authors agree that OLT should not be offered when cardiac or pulmonary support is needed or there is rapidly progressive organ failure since, in these instances, OLT is unlike to offer survival benefit [40]. A recent observational study by Sundaram et al [41] revealed that in patients with impairment of ACLF-3 grade score at listing to a lower grade at transplantation, post-transplant mortality was significantly lower than in patients without this impairment (12% vs. 18%). Improvement in circulatory failure, brain failure, or removal from mechanical ventilation has the strongest impact on post-transplant survival.…”