See “Improved Outcomes in Liver Transplantation in Children With Acute Liver Failure” by Oh et al on page 68.
The article by Oh et al (1) in this issue of the Journal of Pediatric Gastroenterology and Nutrition highlights challenges associated with clinical studies in pediatric acute liver failure (PALF). For instance, we are not provided characteristics or outcomes of children who did not receive liver transplantation (LT), nor of those who were listed for but did not receive LT. The thoroughness of the diagnostic evaluation for individual patients is unknown. Small numbers of patients distributed among risk factors, such as the molecular adsorbent recycling system use (n = 3) and thrombocytopenia (n = 7), make P values of uncertain clinical significance in this highly selected cohort. The authors do not articulate the complexity of LT decision making, and the limitations of organ availability add a unique element to those decisions. Also, the comparative cohort that allows the authors to say that outcomes have “improved” is not well defined. That said, the pediatric LT team at the Asan Medical Center in Seoul, Korea, must be congratulated for achieving the stated graft and patient outcomes following LT for PALF; however, I disagree that their findings should “lessen the ethical pressure” on individual candidates and donors.
PALF is a rare, dynamic, frightful, and, at times, devastating worldwide condition that affects all age groups (2). Etiologies and outcomes vary by age, regional exposures, and resources (3). Treatment is generally supportive unless a diagnosis responsive to targeted therapy, such as acute acetaminophen/paracetamol toxicity, herpes simplex, or autoimmune marker–positive acute liver failure, is promptly identified. LT can be lifesaving, but it carries with it potential complications related to surgery and immunosuppression.
To best use the precious resource of liver donation, whether it is from a living or a cadaveric donor, there should be a reasonable certainty the recipient will die or succumb to significant neurological damage without LT. In addition, one would not knowingly submit a child to LT who would have survived without LT, thereby subjecting both recipient and donor to unnecessary risks or limiting organ availability to others in need of LT. Unfortunately, present predictive models fall short in their ability to predict death (4–6). This is the result, in large part, of the fact that LT interrupts the natural history of PALF.
The dynamic nature of PALF challenges our ability to predict outcome. We know that children, some with advanced encephalopathy, who meet PALF study criteria will survive with their native liver (2). We are familiar with the children listed for LT who would have received an organ had one become available, only to be removed from the list following clinical improvement. These experiences raise the possibility that a portion of children who receive LT for PALF may have survived with their native liver.
Organ availability is enhanced for children with PALF with a living donor option (7). Because graft and patient survival following LT for PALF has improved, we must maintain vigilance to ensure that these children require LT to survive. To that end, ongoing efforts to identify clinical models that reliably predict patient death and survival as well as to identify those for whom LT would not improve long-term outcome (eg, individuals with systemic mitochondrial disease with neurological impairment) must continue.
1. Oh SH, Kim KM, Kim DY, et al. Improved outcomes in liver transplantation in children with acute liver failure. J Pediatr Gastroenterol Nutr
2. Squires RH Jr, Shneider BL, Bucuvalas J, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr
3. Squires RH Jr. Acute liver failure in children. Semin Liver Dis
4. Lu BR, Zhang S, Narkewicz MR, et al. Evaluation of the liver injury unit scoring system to predict survival in a multinational study of pediatric acute liver failure. J Pediatr
5. Sundaram V, Shneider BL, Dhawan A, et al. King's College Hospital criteria for non-acetaminophen induced acute liver failure in an international cohort of children. J Pediatr
6. Bucuvalas J, Filipovich L, Yazigi N, et al. Immunophenotype predicts outcome in pediatric acute liver failure. J Pediatr Gastroenterol Nutr
7. Lee WS, McKiernan P, Kelly DA. Etiology, outcome and prognostic indicators of childhood fulminant hepatic failure in the United Kingdom. J Pediatr Gastroenterol Nutr