The brain gets its say: Hepatic encephalopathy and its evolving role in transplant priority

Abstract

Potential conflict of interest: Nothing to report. See Article on Page 1333 Hepatic encephalopathy (HE), overt and even covert, has a major impact on patient morbidity1 and survival.3 In recent years, the rapidly changing impact of HE on transplant priority and survival on the waiting list has been studied extensively using the United Network for Organ Sharing (UNOS) database and through well‐characterized cohorts.5 The subjective nature of clinical assessment of HE makes including it in organ allocation a divisive issue. Lucidi et al.7 in 2 large cohorts from Italy and Canada defined 1 approach toward solving this issue. Specifically, the authors used HE‐related hospitalizations with grade 2 or higher, that is, overt HE defined by the European Association for the Study of the Liver/American Association for the Study of Liver Diseases guidelines using asterixis and disorientation as diagnostic of HE.8 Stages lower than grade 2 were bundled into a user‐friendly pragmatic no‐HE group that included covert HE.9 A key strength of the study was validation across 2 separate continents with diverse populations and varying transplant organ allocation systems. The authors demonstrated that the contribution of HE to mortality was equivalent to 7 points of Model for End‐Stage Liver Disease (MELD) score. Interestingly, the impact on mortality was independent of the maximum grade of HE achieved beyond grade II, the proximity of the HE episode to enrollment, and the number of recent HE episodes. These findings point toward a biological "“crossing of the Rubicon"” that occurs when a patient reaches grade 2 HE in cirrhosis. The consequences of an overt HE (grade 2 or higher) episode requiring hospitalization are important from a psychosocial and clinical perspective.8 The incorporation of these findings by Lucidi et al.7 into organ allocation remains difficult. The advantages of the MELD score include its objectivity. In contrast, when the Child‐Pugh score was the basis of organ allocation assessment of HE, in the listing the clinician's word was paramount and could not be challenged due to the waxing and waning nature of HE. Interestingly, when HE lost its role in organ allocation after the introduction of the MELD score, the proportion of listed patients coded as grade 3/4 HE in the UNOS database dropped precipitously at a rate far higher than that expected biologically.10 These findings indicate that a portion of the "HE" patients in the Child‐Pugh era were likely overcoded. Ultimately, regardless of which definition of HE is used, it will remain difficult to clinically justify its use. Therefore, as prior studies have demonstrated, corroboration with cognitive, neuropsychological, and neurophysiological techniques may be important objective techniques that could help in the appeal to regional review boards regarding potential listing priority changes in affected patients.3 Moreover, with the introduction of MELD score with sodium for organ allocation, the numeric value to be assigned to HE > grade 2 needs to be recalculated.12 An increase in priority listing for patients with advanced HE is also relevant from a posttransplant recovery standpoint because pretransplant cognitive impairment with HE is consistently associated with a relatively lower recovery after transplant compared with those without these issues.13 Posttransplant liver recovery may not necessarily translate into return to the workforce and independence if cognitive recovery is not complete.15 Therefore, it may be important to consider that “time is brain” when HE patients on the transplant list are considered. This will require objective and reproducible assessment of HE rather than the time‐honored clinical evaluation.