Acute‐on‐chronic liver failure in children with biliary atresia awaiting liver transplantation

Abstract

Objectives Acute‐on‐chronic liver failure (ACLF) is an acute decompensation of cirrhosis complicated by other organ failure and is associated with increased mortality and morbidity. ACLF has not been studied in children with biliary atresia (BA), which is the commonest indication for pediatric liver transplantation (LT) worldwide. This study aims to evaluate ACLF and outcomes in children with BA while awaiting deceased donor LT. Methods This was a subanalysis of the dataset from a prospective cohort study of patients aged 0‐18 years who underwent portoenterostomy for BA and were listed for LT at King's College Hospital, London, between 1999 and 2003. Outcomes included the development of ACLF, mortality, and complications. Results Ninety‐nine (41 male) children were included, and follow‐up was 10 [6.0‐15.0] years. A total of 20/99 children developed ACLF. ACLF was associated with increased mortality while awaiting LT (20% vs 4%; P = 0.03). There were no associations between biochemical parameters at listing and death. Increased bilirubin levels 3 months post‐portoenterostomy was predictive of development of ACLF (AUROC = 0.72, P < 0.01). Age at LT and time on the waiting list in the ACLF subgroup were both lower compared to the non‐ACLF group (P > 0.05). Sepsis and gastrointestinal bleeding were the commonest precipitants of ACLF. Complications included ascites, hepatic encephalopathy, and hepatorenal syndrome; the ACLF subgroup required multisystem support and longer intensive care unit stay. Conclusions ACLF in children with BA awaiting deceased donor LT carries increased mortality and morbidity. This warrants stratification of patients for earlier wait‐listing and prioritization for LT.

Random forest analysis identifies change in serum creatinine and listing status as the most predictive variables of an outcome for young children on liver transplant waitlist

“…This implies that these individuals with lower transplant rates were likely children with acute liver failure (Status 1A) and acute on chronic liver failure (status 1B). In concordance with our findings, a recent study concluded that acute on chronic liver failure in children with BA awaiting deceased donor LT carries increased mortality and morbidity 30 . Subjects with PALF had the lowest transplant rate (59%).…”

“…In concordance with our findings, a recent study concluded that acute on chronic liver failure in children with BA awaiting deceased donor LT carries increased mortality and morbidity. 30 Subjects with PALF had the lowest transplant rate (59%). Even though subjects with PALF constituted only 6.6% of all subjects, they constituted 11.2% and 20.5% of all subjects with bad and good outcomes respectively.…”

A paradigm shift in the intention‐to‐transplant children with biliary atresia: Outcomes of 101 cases and a review of the literature

“…This suggests that a progressing liver dysfunction (thus PELD) is more relevant than malnutrition per se and that children who deteriorate their liver function rapidly should be referred to transplant centers independently of their age and weight. This is in line with a series of recent reports that have highlighted that the risk of death, while waiting for a transplant, was directly related to (a) a relatively late referral to the transplant team, even though these infants were young (<1 year of age at referral); and (b) a poor clinical condition (typically a combination of small weight and malnutrition, severe cholestasis, and a rapidly progressing hepatic dysfunction). Both of these aspects are directly related to each other and represent a failure of our current referral systems; because the failure of a Kasai procedure can be recognized within 2‐3 months of the procedure, and because it is per se an indication for LT, there is little that can explain why children would be referred late or in poor condition.…”

Multiple organ involvement and ICU considerations for the care of acute liver failure (ALF) and acute on chronic liver failure (ACLF) in children

“…Common precipitating events in ACLF appear to vary by region: the hepatotropic viruses are common in studies from Southeast Asia, while sepsis and gastrointestinal (GI) bleeding are common in studies from Europe. The mortality rate for pediatric ACLF in all of these studies ranged between 20-30%, and was five times higher in ACLF compared to CLD (15)(16)(17)(18).…”

“…However, none of these definitions are validated for use in children. In spite of this limitation, many pediatric studies have used these adult criteria to identify ACLF (15)(16)(17)(18). In an attempt to recognize these children and prioritize them more urgently for transplantation, the Organ Procurement and Transplantation Network (OPTN) created criteria for Status 1B (see Table 1) (4).…”