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• W2097188693 abstract "The realization in the 1980s that liver transplantation was feasible in acute liver failure created a need for prognostic indicators to determine the subset of patients most likely to benefit from that intervention. Although many clinical and investigational parameters have been shown to reflect prognosis in acute liver failure, only a few come close to fulfilling the fundamental requirements of a prognostic model in this context—i.e., ease of evaluation, early applicability, and accuracy. The King's College criteria were described in 1989 and created separate models for patients who had and who had not received acetaminophen.1 The parameters tested were basic clinical and laboratory data, resulting in simple-to-use and universally applicable models. The 5 variables included in the group that did not receive acetaminophen were etiology, age, time from jaundice to encephalopathy, serum bilirubin, and coagulation parameters (prothrombin time or international normalized ratio [INR]). More recently, Model for End-Stage Liver Disease (MELD) scores, which have been introduced and validated for use in prognostication in chronic liver disease, were used to assess prognosis in non-acetaminophen-related acute liver failure.2, 3 The 3 variables that contribute to MELD score are serum bilirubin, serum creatinine, and INR. In this issue of Liver Transplantation, Dhiman and colleagues describe another prognostic model and compare its performance to the King's College criteria and MELD scores in a population of patients with proven (mainly hepatitis B) or presumed acute viral hepatitis.4 They identified 6 parameters: age >50 years, jaundice to encephalopathy time greater than 7 days, grade 3-4 encephalopathy, cerebral edema, prothrombin time >35 seconds, and serum creatinine >1.5mg/dL. Any 3 of these factors indicates a poor prognosis. A comparative evaluation suggested that this model was better than both the MELD and the King's College criteria in predicting prognosis. The retrospective study examines a patient population seen between 1996 and 1998. Liver transplantation was not used in the management of acute liver failure in their institution at that time, and this is the latest, and possibly the last, natural history study uncontaminated by transplantation activity to be performed in acute liver failure. This illustrates our reliance on aging data to inform prognostication and our limited ability to evaluate the effect of advances in therapy (e.g., liver support devices)—unless, of course, these treatment modalities obviate the need for transplantation. The current study and the original description of the King's College criteria use the term “early indicators of prognosis” in their respective titles.1, 4 The King's College models concentrated on criteria that were independent of the pattern of organ-specific complications present, and a linkage to the grade of encephalopathy was only required for the subset of patients who had received acetaminophen who did not have refractory acidosis. However, the new model uses 2 parameters that do not easily fit with the concept of “early”—that is, advanced encephalopathy and cerebral edema. The powerful prognostic significance of these clinical complications, especially cerebral edema, is beyond dispute, but these are late events in the clinical syndrome of acute liver failure, particularly in the context of the decision-making process with respect to liver transplantation.5 “Early” as used by Dhiman and colleagues probably refers to the time of presentation to the hospital, and it is important to recognize this fundamental difference when comparing these studies. The King's College model was evaluated as a dynamic process that not only captured the initial set of data, but also subsequently updated it so that the performance of the model was judged by the set of data that deviated most from normal. However, Dhiman and colleagues undertook a comparison by using only a single set of data determined at the time the patient presented to their institution. This is not a valid comparison, and it is regrettable that the mistake has been replicated in other recent publications.6-8 Additional criticisms of the more recent publications include the relatively small numbers of patients included and the absence of validation exercises once the prognostic models had been derived. MELD scores would be expected to be of some value in acute liver failure, given the ample data establishing the prognostic significance of the components of the score. In another publication in this month's Liver Transplantation, Villamil and colleagues report that MELD and Pediatric End-Stage Liver Disease (PELD) scores outperform the King's College criteria and Clichy criteria in assessing prognosis in all patients other than adolescents (who were excluded because of small numbers).8 The concept that MELD/PELD could be used in acute liver failure in the same way it is applied in cirrhosis is attractive, but considerable caution is needed before concluding that this study establishes this to be the case. The authors acknowledge that the sample size is small and that their findings cannot be generalized because of the few underlying etiologies represented in the patient population. Another, but unacknowledged, limitation is the inevitable bias introduced into this analysis by whatever mechanism was used to select patients for transplantation; this has not been explicitly defined. The adaptation of MELD as the prognostic model of choice discards 3 important concepts in our understanding of the natural history of acute liver failure, namely the heterogeneity of the condition (particularly with respect to underlying etiology), the impact of age, and the apparent paradoxes that are characteristic of the hyperacute and subacute cohorts. The former subgroup is associated with the best chance of a spontaneous recovery, as once again observed in this study, despite the greatest prolongation of INR and the high incidence of cerebral edema. The latter subgroup is associated with a poor prognosis despite the less dramatic derangements of coagulation parameters and the low incidence of cerebral edema. Whether MELD scores can overcome these issues (e.g., if the dominance of the INR in the hyperacute category was matched by the dominance of serum bilirubin in the subacute patients giving equivalent scores) remains to be determined by much larger and more sophisticated studies than have been performed to date. Moreover, the age of the patient is very well established as a powerful prognostic indicator (accepting that described thresholds include 30, 40, and 50 years), and if MELD is to prove useful, there should at least be age-modified thresholds defining a poor prognosis.4, 6, 9 There has also been a suggestion that MELD might be developed on an etiology-specific basis, and this is worthy of further consideration.6 One important message to emerge is the common ground that exists between the 3 models under discussion, with only 8 variables being used in total between them. All the variables remain standard clinical and laboratory parameters and thus preserve the objective of keeping prognostication as simple and as widely applicable as possible. Another potentially valuable lesson from this study, along with another recent one, is that the prognostic models of the future should be multiphasic and should capture critical data at key time points during the evolution of the illness.4, 6 The prognostic models of the future also need to connect with the important but underdeveloped evaluation of prognosis after liver transplantation. This is important to avoid futile transplantation in individual patients as well as to obtain the greatest possible benefit from the pool of organs allocated to patients with acute liver failure. The evaluation of prognostic models that fall short of the ideal is strongly influenced by whether positive or negative predictive accuracy is deemed to be the most important function of the model. Preference for positive predictive accuracy favors the individual patient and strives to ensure that all patients who need a transplant get one. The downside of this approach is that the error rate translates to unnecessary transplantation. Preference for negative predictive accuracy minimizes unnecessary transplantation and ensures that an excessive proportion of a limited resource is not diverted to the management of patients with acute liver failure. However, the error rate with this approach translates to missed opportunities and avoidable deaths. Although this tension persists between philosophical attitudes, it is inevitable that some will see prognostic models as (imperfect) tools supporting clinical practice, while others will view them as anchors inhibiting progress." @default.
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• W2097188693 title "Prognostication in acute liver failure: A tool or an anchor?" @default.
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