Liver transplantation (LT) is a lifesaving treatment for children with end-stage liver disease (ESLD). As immunosuppressive and surgical techniques have improved over time, long-term patient and graft survival rates have continued to increase. With recent 5-year patient survival rates reported as being greater than 85% in the United States, it is important to look beyond patient and graft survival rates and biomedical (e.g., laboratory or radiological) outcomes. Optimizing the quality of a patient’s life is as important as the number of life years restored after LT for recipients and families. Attention to the broader determinants of health encompasses mental, emotional, cognitive, social, and functional dimensions and psychosocial considerations and challenges.
Quality of life (QOL) refers to the broader definition of “a state of complete physical, mental, and social well-being, and not merely the absence of disease.” Psychosocial health is an important QOL domain, encompassing mental, emotional, social, psychological, and psychiatric dimensions of wellness. Psychological and psychiatric challenges in children with ESLD awaiting LT may present with unique clinical susceptibilities. Numerous studies reveal an increased risk for lower QOL, impaired psychosocial outcomes, and increased family distress in children who have undergone LT, with lifelong immunosuppression, continuing surveillance clinic visits, and medical treatment cited as disease burdens for this patient population. Earliest identification and timely implementation of intervention strategies targeting post-transplantation psychosocial outcomes will help optimize outcomes in children who have undergone LT. ,
This chapter will examine the psychosocial outcomes following pediatric LT, discuss predictors and risk factors for the development of impaired psychosocial outcomes after pediatric LT, and recommend interventions targeting these specific domains of functioning ( Fig. 43.1 ).
Assessment of Psychosocial Aspects After Pediatric Liver Transplantation
A patient-reported outcome is any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else. A patient-reported outcome pertains to the patient’s health, quality of life, or functional status associated with healthcare or treatment. Patient-reported outcome measures (PROMs) are tools and instruments for patients to complete about symptoms, functionality, and physical, mental, and social health. PROMs measure aspects of a patient’s health status at a particular point in time during an illness or with a health condition. These tools are essential to understanding whether healthcare services and procedures make a difference to patients’ health status and QOL and provide insight on the effectiveness of care from the patient’s perspective, complement existing information on the quality of care and services provided, such as clinical, administrative, and patient-reported experiences, which can serve to inform decisions better. PROMs provide essential information for achieving health system goals by recognizing the patient’s perspective in regard to understanding how healthcare services and procedures make a difference to his or her health status and QOL. The impact of a treatment or intervention on a patient can also be better ascertained by reviewing PROM data before and after a therapeutic intervention. In pediatrics, PROMs can also be completed by a parental or guardian proxy. Understanding the parent’s perspective can be insightful because, in some cases, owing to a child’s cognitive immaturity and continued dependency, parents may be better able to rate some aspects of their child’s QOL. PROMs have the ability to capture the subtler short- and long-term implications of LT that will be essential for providing improved patient care and for informing improved organ allocation policies.
QOL assessment for pediatric LT recipients can be evaluated using generic and disease-specific PROMs. Commonly used generic QOL measures include the Pediatric Quality of Life Inventory (PedsQL) Generic Core scale 4.0, Child Health Questionnaire–Parent Form 50 (CHQ-PF50), and Child Health Questionnaire–Child Form 87 (CHQ-CF87). These generic tools are limited by inadequate capture of the unique and distinct clinical issues confronting pediatric LT recipients. Disease-specific, health-related QOL (HRQOL) measures have the advantage of offering greater sensitivity and specificity and include questions that focus on treatment- and disease-related challenges. The availability of two validated disease-specific tools for this patient population include the Pediatric Quality of Life Inventory 3.0 Transplant Module and Pediatric Liver Transplant Quality of Life tool (PeLTQL). Routine incorporation of these disease-specific tools into clinical care, such as at annual clinic visits, may enable earlier identification of issues and targeted interventions or supports for the patient and family.
Healthcare providers’ perspective on the pediatric LT recipient is important to consider. Miserachs et al. identified elements noted by healthcare providers that both enhance (improved physical health, peer relationships, and activities of daily living) and challenge (need for immunosuppression, transplant follow-up, and restrictions) the multidimensional domains of HRQOL.
Health-Related Quality of Life
HRQOL is defined as a multidimensional construct that examines both the impact of an illness in addition to its effect on functioning and well-being. QOL is a broader term than HRQOL because it includes evaluation of non-health-related features of life, whereas HRQOL is connected to an individual’s health or disease status. HRQOL enables understanding of the distinction between aspects of life related to health and addresses aspects of overall QOL affecting physical and mental health, including health perceptions and their correlates, health risk, and conditions. Factors contributing to impaired HRQOL following pediatric LT can be divided into nonmodifiable and modifiable risk factors ( Table 43.1 ).
|Non-Modifiable Risk Factors||Modifiable Risk Factors|
|Primary Indication for LT|
|Time since LT|
Non-Modifiable Risk Factors
Non-modifiable risk factors, such as age, gender, and household factors, are variables that affect an outcome but cannot be altered ( Table 43.2 ).
|Non-Modifiable Risk Factor||Multicenter (M) or Single-enter (S) Study||Study, Year||Country||Population Size ( n )||HRQOL Tool(s) Used||Key Findings|
|Gender||M||Alonso et al. |
|United States and Canada||441||PedsQL 4.0 Generic |
PedsQL Cognitive Functioning Scale
|Male gender was associated with lower HRQOL scores.|
|S||Alba et al. |
|Chile||49||PedsQL 4.0||Males reported lower scores in physical and social functioning compared with females.|
|S||Cole et al. |
|United States||45||ITQOL||Males reported higher scores in general and global health perception compared with females.|
|Age at transplantation||M||Alonso et al. |
|United States and Canada||441||PedsQL 4.0 Generic |
PedsQL Cognitive Functioning Scale
|Parent HRQOL report identified increasing age at transplantation as a predictor of generic HRQOL.|
|S||Alba et al. |
|Chile||49||PedsQL 4.0||As patients advance in age, physical HRQOL trended downward, and a significant difference was only experienced as poor in adolescents.|
|S||Bucuvalas et al. |
|United States||77||CHQ-PF50, |
|Age at transplantation was a significant predictor of physical health, with older patients reporting worse HRQOL.|
|Primary indication for LT||M||Feldman et al. |
|United States||263||PedsQL 4.0||Patients with biliary atresia reported higher physical HRQOL scores compared with all other indications.|
|M||Ng et al. |
|United States |
|167||PedsQL 4.0||There was no difference in self-reported HRQOL for patients with different causes of liver disease.|
|M||Alonso et al. |
|United States||55||PedsQL 4.0||There was no difference in self-reported HRQOL for patients with different causes of liver disease.|
|Time since liver transplantation||S||Cole et al. |
|United States||45||ITQOL||The time elapsed from transplantation was a significant predictor of functional health.|
|S||Gritti et al. |
|Italy||36||WISC||The time elapsed from transplantation was associated with an increase in HRQOL scores.|
|Household factors||M||Alonso et al. |
|United States and Canada||441||PedsQL 4.0 generic |
PedsQL cognitive functioning scale
|A single-parent household was associated with a lower HRQOL.|
|S||Devine et al. |
|United States||82||CHQ-CF87||Lower parental income was associated with a lower HRQOL.|
|S||Kosola et al. |
|United States||66||PedsQL 4.0, SF-36, DISF-SR, AUDIT||Lower maternal education (less than college) was associated with a lower HRQOL.|
Patient Age at Liver Transplantation
Older patient age at the time of pediatric LT has been shown by multiple studies to affect HRQOL. In a multicenter study using data from the Studies of Pediatric Liver Transplant (SPLIT) database, older patient age at the time of LT was associated with worse physical HRQOL as assessed by the PedsQL physical domain score, with a pronounced effect in the adolescent period. School-age patients reported impaired psychosocial HRQOL, whereas children younger than 12 years reported better overall HRQOL compared with adolescents, as assessed by the PedsQL. Adolescence is also a vulnerable period of increased risk for medication non-adherence and graft loss. Although age at transplantation is non-modifiable risk factor, understanding that certain age groups are more vulnerable, with adolescents being most at risk, can help healthcare teams to focus on this susceptible subgroup of patients and work toward targeted interventions and provision of additional supports.
The relationship between gender and HRQOL in pediatric LT recipients remains unclear. Lower HRQOL scores were noted in male pediatric LT recipients from a multicenter study of 441 pediatric LTrecipients, as well as a single-center study. Conversely, another single-center study reported higher HRQOL scores for males. Differences in HRQOL by gender may be attributed to the fact that studies examining gender as a predictor of impaired HRQOL may not have accounted for other confounding variables that may affect HRQOL such as time of LT and other psychosocial factors, including age at LT and mental health. Future studies should target intrinsic psychological factors specific to males and females, such as resiliency, social support, and stress.
Results from the Functional Outcomes Group (FOG) revealed that patients with primary disease other than biliary atresia were more than twice as likely to have a lower physical function score. Conversely, the primary cause of liver disease had no impact on reported HRQOL in two multicenter studies. A possible explanation for this discrepancy could be the differing conditions at time of transplantation, such as age and family factors. Additionally, a Canadian-European multicenter international study found impaired coping and adjustment domain HRQOL scores among biliary atresia patients who completed the PeLTQL (Pediatric Liver Transplant Quality of Life) Questionnaire, a disease-specific HRQOL tool validated in 10 different languages.
Lower household income and single parental marital status are associated with a lower HRQOL. Family-associated factors may challenge the management of the daily responsibilities involved in caring for a child with a chronic illness, and it was found that parental income predicted not only baseline physical functioning but physical functioning at 18-month follow-up of teenagers who had undergone solid organ transplantation. Parental marital status also predicted generic HRQOL, with a lower HRQOL reported by patients from single-parent households compared with their counterparts from dual-parent households. Impaired HRQOL may be related to poor family supports and coping mechanisms, as well as decreased access to resources among single-parent households. Maternal employment has also been linked with post-LT outcomes. It was found that parent HRQOL scores trended lower in mothers who were unemployed before their child underwent LT, although the difference did not reach statistical significance. More data are needed to study the impact of parental employment on life after pediatric LT.
Distance from an LT center has also been implicated to affect HRQOL outcomes, with children living in the same city as the transplantation center reporting better social functioning HRQOL than those living in other cities.
Modifiable Risk Factors
Modifiable risk factors affecting HRQOL include medication adherence and sleep, some of which may be targetable for intervention.
The prevalence of non-adherence to immunosuppressive (IS) therapy in pediatric LT recipients has been found to range from 15% to 53%, with a correlation to HRQOL. In three separate studies by Fredericks and colleagues, non-adherent patients reported lower HRQOL on the CHQ-P50. In a follow-up study, non-adherent patients reported lower HRQOL scores on all domains of the CHQ-PF50, PedsQL, and CHQ-CF87. Interventions targeting barriers to IS adherence are warranted because the development of clinical events arising from non-compliance with prescribed immunosuppression medications leads to the subsequent need for invasive investigations and procedures, such as hospitalizations, liver biopsies, and augmentation of antirejection medications such as steroids, thus affecting HRQOL.
Sleep-related breathing disorders predicted scores on all HRQOL subscales, except school functioning. Excessive daytime sleepiness and snoring had the greatest impact on the HRQOL of recipients of live donor LT. Additionally, pediatric LT recipients reported more symptoms of sleep-disordered breathing, excessive daytime sleepiness, daytime behavior, and restless legs. Parents also confirmed sleep impairments of their children, with nearly 25% of parents endorsing clinically significant symptoms of sleep-related breathing disorders in them. Clinically significant sleep problems were more common among children with lower total HRQOL scores. Preemptive targeting of attention to and education about good sleep hygiene highlight the importance of sleep quality and its impact on HRQOL after pediatric LT.
Health-Related Quality of Life of the Pediatric Liver Transplantation Recipient Compared With Other Groups
Pediatric LT recipients self-reported comparable scores as children with cancer and chronic liver disease and lower scores compared with children with type 1 diabetes, specifically in the domains of physical health and general health perception. Findings suggest that differences in the trajectory of different disease courses influences the HRQOL.
No difference in self-reported HRQOL reports among recipients of liver, heart, lung, and renal transplants has been found. This has been attributed to similarities in post-transplantation care, including continued medical monitoring, frequency of hospitalizations, and daily medication requirements.
When compared with a healthy population, pediatric LT recipients reported lower HRQOL. A multicenter cohort of 10-year survivors of pediatric LT recipients in the United States and Canada reported lower HRQOL when compared with age-matched healthy controls. Pediatric LT recipients also reported increased impairment in the domains of emotional and school functioning when compared with their healthy counterparts. Pediatric LT recipients differ significantly from healthy controls—participation in the transplantation process has long-term effects influenced by experiences such as long-term follow-up and the burden of ongoing medical care, which can disrupt patients and family’s routines and thus affect HRQOL.
Interventions Targeting Health-Related Quality of Life
Studies examining strategies or interventions aimed at improving HRQOL have been very limited. One study evaluated the effectiveness of a 6-month peer-to-peer mentor program intervention directed at improving adherence and HRQOL. Adherence to IS therapy did show improvements, however; after participation, there were no statistically significant differences in HRQOL between the intervention and control groups. Thus given the impact of modifiable and non-modifiable risk factors on HRQOL, future research is warranted to examine ways to target improving HRQOL, with continuous monitoring and development of innovative interventions.
Mental health has been shown to be impaired in pediatric LT recipients, especially in adolescents. Adolescents are particularly vulnerable owing to developmental challenges such as a desire for autonomy, poorly developed abstract thinking, and identity development. Rates of anxiety and depression among adolescent LT recipients are higher than in the general population, reported to be as high as 17%. Specifically, associations were found between patients’ emotional response to their illness and rates of depression and anxiety; that is, patients who reported an increased disease burden of their illness more frequently reported depression and anxiety. Suicidal ideation was also reported among adolescent LT recipients, which indicates that this risk is serious and needs to be identified and ameliorated with evidence-based interventions targeting mental health and issues that are experienced in adolescence.
Neurodevelopment is an important milestone of development and encompasses areas of cognitive function, academic achievement, and school performance. Impaired neurodevelopmental, cognitive, and academic outcomes have been documented in survivors of LT, including a greater probability of intellectual deficits and learning disabilities compared with the healthy population. Key findings are summarized in Table 43.3 .