Cognitive Function, Self-Management and Graft Health in Pediatric Liver Transplantation



This editorial examines the potential relationship between allograft health and cognitive function in long-term survivors of pediatric liver transplantation. See article by Kaller et al on page 2956.

Liver Transplantation (LT) Is a Well-Established and Effective Treatment for Irreversible and End-Stage Liver Disease

The goal for LT recipients is to ensure graft health, functional health and freedom from the complications of immunosuppression. With advances in organ preservation, operative techniques, immunosuppression and prevention of infection, 1- and 3-year patient and graft survival has markedly improved. Consequently, research focus has shifted to include strategies to improve long–term graft function and health. The strategies for pediatric and adult LT recipients have important distinctions. In adults, the indications for LT are frequently conditions that may recur. Consequently, clinical strategies and research are targeted to defining risk and prevention of disease recurrence. In children, the most common indications for liver transplantation are diseases not likely to recur after transplantation. Most pediatric LT recipients are under age 5 years at the time of transplantation. This is a period of rapid brain development and critical for cognitive development, the latter often not assessed as an outcome metric. Finally, the potential ceiling for life years gained for children is higher, further emphasizing the importance of the challenge to manage long–term graft health.

What Is Our Current Understanding of Outcomes in Long-Term Pediatric LT Survivors?

While 10-year patient survival rates approximate 80%, allograft failure at 5 and 10 years after liver transplantation is 25% and 35%, respectively, even given the infrequency of disease recurrence. Moreover, a substantial proportion of long–term pediatric liver allografts exhibit chronic portal inflammation, interface hepatitis and/or fibrosis even in the face of normal liver tests [1]. Ng et al [2] reported that less than one-third of 10-year survivors met the criteria for an ideal 10-year survivor, defined as normal liver tests and freedom from the most common sequelae of immunosuppressive medications. The estimate is probably low since graft histology was not used to define allograft health. The cause of late allograft dysfunction is likely multifactorial. Nevertheless, nonadherence and failure of self-management certainly play a role since we know that nonadherence contributes to late rejection and is associated with graft loss.

Cognitive Status Is Compromised in Pediatric LT Survivors

In the present issue, Kaller et al [3] provide insight into the cognitive status of pediatric LT recipients. They conducted a cross-sectional single-center study to define the prevalence of cognitive impairment in a cohort of pediatric LT recipients. Subjects were between 6 and 18 years old at the time of testing and were at least 1 year after transplant. A revised version of the Wechsler Intelligence Scale was used to assess verbal comprehension, perceptual reasoning, working memory and processing speed. The strategy was critical because it assessed working memory and reasoning, a critical issue for outcomes in this population. The authors observed a shift of the overall study population toward lower scores compared to age- and gender-matched controls. Subjects with genetic or metabolic disease performed worse. Height at transplant and days in the ICU were critical predictor of poor function and explained more than 25% of the variance. The work is aligned with previous observations by Sorensen et al [4] who reported deficits in intelligence and learning as early as 5 years of age, including specific deficits in cognitive executive functions such as planning, working memory, task initiation and self-monitoring. While decreased cognitive function is by itself a critical outcome metric, it also poses a challenge to self-management and may ultimately adversely affect allograft health.

Might Decreased Cognitive Function Impact Long-Term Allograft Health?

The population of pediatric LT recipients serves as a disease model for chronic illness. According to Wagner et al [5], best outcomes for patient populations with chronic conditions require a commitment to self-management. Cognitive abilities are essential to developing competence in self-management of any chronic health condition. Neurocognitive dysfunction impairs adherence to medical regimens [6], and we know that medication nonadherence contributes to graft dysfunction and rejection episodes. If cognitive function, especially executive function, is compromised, then it may predispose affected patients to failure of self-management and consequently late rejection and allograft injury. Cognitive dysfunction must be considered when developing strategies to improve self-management as adolescents take increasing responsibility for their health management. We need to clarify the relationship between cognitive dysfunction and allograft health controlling for social and demographic factors. Perhaps also, we should reevaluate prioritization timing of transplantation in young children with irreversible liver disease during periods of rapid brain growth.


The author of this manuscript has no conflicts of interest to disclose as described by the American Journal of Transplantation.