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• W3010899110 abstract "See “Development of a Prognostic Score to Predict Mortality in Patients With Pediatric Acute Liver Failure” by Lee et al on page 777. The search for accurate prognostication in paediatric acute liver failure (PALF) continues in this month's Journal of Pediatric Gastroenterology and Nutrition with a study from South Korea (1). Lee et al have developed and validated a novel algorithm for survival/nonsurvival in children with PALF presenting 2000–2018. With improvement in supportive care and in the era of availability of live-related liver transplantation (LT), determination of those with PALF who will survive, and thus not require LT, remains an important question. This is in the hope of both expediating the listing for an organ in those who will require it and to avoiding over-transplantation in those who will spontaneously recover. Several systems exist to predict mortality in adults with ALF, though sensitivity and specificity vary. The King's College Hospital Criteria (KCHC) developed in 1989 (2) have been widely used since that time though advances in liver critical care may influence its accuracy. Meta-analysis has shown a low sensitivity of 58% with a specificity of 89% (3). The Clichy criteria are based on Factor V levels and the presence of hepatic encephalopathy, again with limited sensitivity. The use of MELD (developed initially for another purpose), was more sensitive as a prognosticator but with limited specificity (3). Intensive care scores, such as SOFA or APACHE II can give meaningful predictive results, again, despite the fact they were not developed specifically for this purpose (4). The dynamic nature of ALF was tackled by Kumar et al in an adult cohort (5). This group used parameters of the change in arterial ammonia, serum bilirubin and in INR over the first 3 days of admission (ALFED score) reporting an AUROC of 0.91 for prediction of mortality. LT did not interrupt the natural history of ALF in these patients and so the study offers a clean look at survival in this population and is not replicable in regions where LT is more freely available. The applicability of adult scoring systems to children and infants with PALF remains limited (6). Aetiology of liver failure in this population and particularly in infants, is considerably different to that in adults, with subsequently different outcomes. In addition, the very definition of ALF in children differs from that in adults as it may or may not include hepatic encephalopathy, recognising the inherent difficulty in recognising encephalopathy as a definite sign in very young children. Previously described scoring systems in children encounter the same issues as in adults, and are further hampered by smaller numbers of children with more heterogenous diagnoses. Applying KCHC to PALF to children in the PALF study database yielded a low sensitivity for determining mortality (61%) (7). The Paediatric End-Stage Liver Disease Score (PELD), an aid to prioritisation in organ allocation, again performs with varying sensitivity and specificity, though small study using PELD in PALF found both to be >80% for prediction of poor outcomes (8). The Liver Injury Units (LIU) system was developed as a score to derive a likelihood of death. Peak values of INR and bilirubin were used in a large dataset from the PALF Study Database, finding an AUROC of 0.81 for death/LT (9). Though the LIU system has its own limitations, it has been used in a way that is more dynamic than previous approaches. The most effective scoring systems or prediction of mortality without transplant have been developed for single aetiologies, for example, the Wilson's score predicting death without transplantation in children presenting with ALF secondary to Wilson disease (10). In this edition of Journal of Pediatric Gastroenterology and Nutrition, Lee et al have taken on this challenge hypothesising that a dynamic score will better reflect acute liver failure, which is a dynamic and rapidly changing entity. The authors have built an algorithm using peak levels and degree of change in INR, bilirubin, and ammonia over the first 7 days following admission. The cohort is derived from sequential children presenting with ALF to 2 transplant centres in Korea over almost 2 decades. The children are grouped retrospectively into those who survived with native liver, those who died, and those who underwent transplant. Though there is inherent bias injected by altering the natural history of ALF with transplant, this is, of course a real-life study, and where there is the availability of transplant, the only possible approach. The nonsurvival group and the transplant group are similar in characteristics. Interestingly, of the 21 children who died in the development cohort, 17 were not listed for transplant. Though 3 had underlying medical conditions, which contraindicated transplant, the remainder were reported as too clinically unstable to undertake transplant, though no further detail is given to this effect. Again, this leads to a concern that there may be an inherent bias in analysing these data. The PALF-Delta score developed in the first cohort uses the change in peak bilirubin, change in daily INR, and peak ammonia to reflect the dynamic nature of the disease. Change can be assessed prospectively on a day-to-day basis but predicting what will be the peak bilirubin or ammonia is obviously much more difficult to do in real-time. Despite these issues, the authors have heralded a step-change in scoring systems for prognostication in PALF. Though imperfect, the authors describe a dynamic model to separate out those who will die without transplant and those who recover with their native liver. Identifying those with the capacity of the liver to regenerate may allow the effective use of liver-assist devices and bridging strategies, which are now most often employed without a measurable understanding of the regenerative potential of an individual liver. Liver transplant, is now a very successful and clearly often a lifesaving procedure. It is, however, accompanied by a lifetime of immunosuppression with a multitude of side effects and consequences in terms of quality of life, education, and employment. Though organ availability is still a major problem, advances in live-related liver transplantation present a practical approach to managing PALF in a timely manner. Thus, the critical question becomes not which child will die without transplant but who will go onto live a long life with their native liver if successfully bridged across the acute crisis." @default.
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• W3010899110 date "2020-03-12" @default.
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• W3010899110 title "Prognostication in Paediatric Acute Liver Failure: Are We Dynamic Enough?" @default.
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