Challenges for Young People With Liver Disease Including Transition to Adult Services

Long-term outcomes following liver transplantation (LT) are inferior for adolescents and young adults in comparison with younger children and adults. Adolescence is a transitional stage of psychosocial development and a time of rapid physical growth and change. This developmental period includes sexual maturation, cognitive development, emotional changes, and the transition from total social and economic dependence to relative independence. Insight into the unique neurodevelopmental changes that occur in young people during adolescence and continue into the mid-20s allows us to better understand the particular challenges young people face during this developmental period. The impact of liver disease on pubertal and cognitive development is recognized and is likely to influence long-term health-related quality of life, including education and subsequent employment prospects. Whereas nonadherence to treatment, medical advice, and clinic appointments is considered developmentally appropriate in this population, it is a concern for all those working with young people and often challenging to manage. In the midst of all these changes, young people are expected to move on from pediatric to adult-centered services, often with little preparation or support.

In the first part of the chapter, we will elaborate on adolescent development in general and its implications for young people after LT, including growth and puberty and cognition.

Adolescent Development

Neurodevelopmental Changes During Adolescence

In terms of neurological development, adolescence is considered to stretch from the onset of puberty well into the mid-20s. It is a unique period, distinct from both childhood and adulthood, such that some characteristics, for example, spatial ability, actually decline with the onset of puberty, whereas others, like perception of danger, are temporarily altered during this period. Normal fears of danger are temporarily suppressed during adolescence, a shift evolutionarily rooted in the need to leave home and explore new habitats. Studies have found that adolescents fail to change their appraisal of risky situations even after being warned that the hazards are greater than they expect. This leads to the belief that they will escape the worst consequences of certain actions, a bias that only begins to diminish by the mid-20s. Steinberg describes adolescence as a period of “especially heightened vulnerability” resulting from potential disjunctions between the developing brain and the behavioral and cognitive demands placed on the young person. It is highly likely that this bias affects young people’s ability to adhere to lifestyle recommendations and medication.

Typically, during adolescence, emotional states run high, including anxiety levels. Young people feel the whole range of emotions as adults but have yet to develop the sophisticated executive functioning skills required to manage them. Attempting to make young people anxious about their condition by telling them off for poor adherence or management of their condition is more likely to lead to avoidance and subsequent disengagement with health professionals rather than to a change in their behavior.

Increases in impulsivity, delay discounting (the extent to which consequences decrease in effectiveness to control behavior as a function of there being a delay to their occurrence), reward seeking, and emotional reactivity are noted in adolescence, which make this period a time of heightened vulnerability of patients to taking risks with their health. This sense of being invincible and bulletproof can have helpful implications in the process of adolescence because it gives young people the courage to separate from parents and manage other changes in a developmentally appropriate and expected way (at least within Western models of adolescence). However, these feelings of invincibility can have more negative consequences for self-management of chronic illnesses. For example, adolescents who feel they are invincible would be more likely to believe that any negative consequences of missing medication will not happen to them.

Peer acceptance is key in adolescence, and young people consistently report a strong desire to feel normal at this age. Young people will go to great lengths to appear normal, and having a chronic condition impacts this desire and is perceived as unfair. This can explain why previously adherent adolescents suddenly stop taking their medication and engage in more risk-taking behaviors.

Growth and Puberty

Puberty involves significant changes to a young person’s body, which typically occur simultaneously with an increase in the importance of appearance and peer acceptance. The reciprocal interaction between chronic illness and puberty on various levels, including biological, psychological, and social, has been comprehensively illustrated by Suris and colleagues; however, it remains poorly investigated in the setting of liver disease and LT.

The Studies of Pediatric Liver Transplantation (SPLIT) registry found that 20% of a large cohort of pediatric liver transplantation (PLT) recipients had linear growth impairment at their last follow-up. With regard to pubertal development, only 61% of girls and 58% of boys aged 16 to 18 years had reached Tanner 5 pubertal stage (compared with 100% of a normative population). Even in those reaching Tanner stage 5, 11% had a linear growth impairment. In a more recent study, height at time of LT was the most important predictor of long-term growth, with catch-up growth only occurring within the first 2 years after transplant. Whereas pubertal delay is common in young people with chronic health conditions, its prevalence in chronic liver disease and LT recipients is not well documented. What is known in female adults is that end-stage liver disease alters the normal physiology of the hypothalamic-pituitary-gonadal axis and disturbs estrogen metabolism, which affects sexual function. This appears to settle after LT, as demonstrated in an adult study where 28% of 64 women with liver disease had irregular menses and 30% had amenorrhea before transplantation, whereas 95% of those under 46 years of age reported a normal menstrual cycle within the first year post-LT.

The psychological impact of both delayed or impaired puberty and growth should not be underestimated, especially considering how young people want to be normal and fit in. One study found an association between short stature (i.e., height for the lower 15% of the sample) and poorer body image in males but no association for females. This finding is consistent with that of a study by Tiggemann. A study from our center in 80 young people with liver disease (30% post-LT) demonstrated a poorer body image perception compared with the general population, and interestingly this did not appear to be related to having a surgical scar or perceived side effects of immunosuppressive medication, as body image was comparable across liver disease diagnoses.

Cognitive Development and Challenges in the Liver Transplant Setting

Cognitive ability in children and young people (CYP) is highly related to health behaviors and is predictive for educational attainment and subsequent occupational outcomes. Research indicates that just 18% to 44% of adult LT recipients return to employment post-transplant, which is considerably lower than other solid-organ transplant recipients and the national average. This highlights the importance of a better understanding of cognition and its mediating factors in this population to promote a better quality of life for young people entering adulthood post-LT.

In transplant recipients, cognitive outcomes appear to be negatively associated with longer illness duration or time spent on the transplant waiting list, and the most significant predictor for specialist education requirement post-transplant is the pre-transplant requirement for additional support. This suggests that most cognitive deficits requiring specialist education provisions originate before transplantation, and it highlights the importance of early exploration of cognition in all CYP with liver disease, including those pre-transplantation.

It is important to highlight that cognition goes beyond general intelligence, which has been the focus of most studies to date. Ee et al. demonstrated that, despite normal IQ scores, young LT recipients had difficulties in executive functioning, particularly in self-regulation, planning and organization, problem solving, and visual scanning, deficits that are also reflected in the adult literature.

Adolescence is a challenging period for young people, and in particular for those with a chronic condition. The second part of the chapter will focus on challenges such as adherence, mental health, and acquiring skills to manage a chronic condition.

Challenges for Adolescents

Outcome data in the transplant setting are inferior for those transplanted between the ages of 12 and 17 years compared with younger and older cohorts, irrespective of the type of organ transplanted. In addition, young adults 18 to 24 years of age are more likely to experience disparities on the waitlist for LT and have worse outcomes compared with other age groups. This supports the World Health Organization’s decision to acknowledge “young people,” 11 to 24 years of age, including both adolescents and young adults as a distinct population requiring a dedicated healthcare provision. This new definition challenges both pediatric and adult health professionals, and young people are often left with minimal transition provision or support when moving from one service to the other, a process defined by age rather than readiness. For example, there are a number of factors inherent to the developmental period of adolescence that could impact medication adherence and some preliminary evidence that poorly managed transition between pediatric and adult health services further compromises adherence.

To Adhere or Not to Adhere

Nonadherence is a complex and multifactorial process linked with various barriers related to illness and treatment demands as well as developmental and psychosocial factors, illustrated in Fig. 46.1 . As well as immunosuppressive medication adherence, young people post-transplant are required to self-manage a number of behaviors, including scheduling and attending clinic appointments, maintaining a healthy lifestyle, and avoiding alcohol, smoking, substance abuse, poor diets, and unsafe sexual practices. In particular, non-adherence with immunosuppressive medication is thought to explain an important part of the elevated levels of transplant loss in the adolescent population, as well as in children and adults. Depending on the method used to measure it and its definition, prevalence of nonadherence is estimated to be between 15% and 40%. Of concern is the higher prevalence of nonadherence and disengagement with health services during the transition from pediatric to adult health services. Health professionals typically rely on subjective methods, including self-reported adherence, in the absence of a gold-standard method. More objective measures, such as electronic pill counting (boxes that record when medication is taken out of them), result in higher rates of reported nonadherence but are cumbersome and expensive to use. Although a central component of adherence assessments that is used frequently in both research and clinical practice, this indicates that self-reported measures of adherence used in isolation are prone to underreporting, which should be considered in their interpretation.

Fig. 46.1

A wide range of potential factors, including treatment demands, illness demands, social factors, psychological factors, developmental factors, and healthcare provider.

In LT, a higher medication level variability index (MLVI), calculated as standard deviation values of consecutive immunosuppressive measurements of tacrolimus was found to correlate with late acute rejection episodes in all age groups. Typically, female gender, lower socioeconomic status, younger age, and single-parent households have been associated with nonadherence. However, a recent study in children post-LT by de Oliveira et al. found MLVI greater than 2 to be more prevalent in families with higher income. Nonadherence therefore remains a challenging topic to study, with a lack of randomized controlled trials. Available studies also do not include those patients who have disengaged from health services.

Exploring nonadherence should be part of the routine management of all patients (irrespective of age) and approached in a nonjudgmental fashion to encourage disclosure and engagement. Health professionals should know that, in young people, nonadherence is considered to be relatively developmentally appropriate and not suggestive of distrust in healthcare professionals or, equally, rejection on the part of the adolescent.

Simplification of medication regimens should be considered because conversion to the slow-release form of tacrolimus was associated with a fourfold decrease in biopsy-proven acute rejection in a cohort of 129 adults and young people ( n = 15) treated with a once-daily regimen compared with a group ( n = 60) taking twice-daily tacrolimus, and it included improvement in MLVI. Practical reminder systems including pillboxes, charts, or electronic alarm systems can help because forgetfulness and poor organization are the most common reasons for suboptimal adherence to treatment. In contrast, intentional nonadherence tends to be largely associated with patient and illness beliefs, and a more formal psychosocial assessment and targeted counseling are required to address it.

A prospective multisite study that included 400 pediatric and adolescent LT recipients who were monitored over 2 years demonstrated the fluctuating nature of nonadherence. Adherence status (defined by MLVI) between year 1 and year 2 changed for almost one-quarter of the sample: from adherent to nonadherent in 9.9% and vice versa in 13.9%. Patients who were nonadherent during the first year were likely to remain nonadherent. This supports ongoing assessment of adherence as part of the clinic consultation and highlights the importance of not labeling patients based on previous behavior.

The impact of psychosocial stressors on clinical care and nonadherence to treatment can be significant. A case note review of 34 patients attending our liver transition clinic who were referred to the clinical psychologist and social worker because of concerns of nonadherence demonstrated a high prevalence of intentional nonadherence (35%) or a combination of intentional and unintentional nonadherence (50%). The most common presenting problem for these young people were relationship difficulties, and a third of patients disclosed a history of childhood abuse, unknown to the clinical team.

Mental Health

Qualitative research shows that young people with chronic illness experience extra restriction, pain, and additional worries relative to their healthy peers because of the demands of living with and managing a health condition during adolescence. Symptoms of chronic illness, restrictions on functioning, and the need for complicated treatment regimens are likely to interfere with many aspects of adolescent life and to cause frustration. There is evidence that the high rates of depression and anxiety found in adolescents are further exacerbated by chronic illness. This appears to be true for young people with liver disease, including those post-LT. Given that poor mental health is linked to worse physical health via increased nonadherence to medication and disengagement from services, it is important that mood and emotional well-being in young people post-LT are considered routinely as part of good clinical care.

Young people with LTs face the same normative life changes and challenges as their healthy peers but with the additional challenges posed by their condition. A recent study of our patients found that among 51 young LT recipients, 9.8% screened positive for a major depressive disorder, and 17.7% had a probable anxiety disorder. These rates are considerably higher than rates found in the adolescent general population but comparable with levels found in other adolescent chronic illness populations and, indeed, other forms of chronic liver disease in this study. Within our group of young people post-LT, greater levels of depression were intertwined with specific beliefs about their condition (lower sense of personal control and increased perceptions of illness identity, concern, and emotional response) as measured by the Brief Illness Perception Questionnaires. Although healthcare often focuses on education regarding CYP’s condition and treatment, these data suggest that perceived lack of knowledge does not relate to distress levels. Further work is needed to understand the causality in the relationship between negative beliefs about illness and depression/anxiety; however, in the meantime, it is important to consider young people’s beliefs about their condition, particularly in those presenting with distress.

In line with our experience clinically, almost half of young people with liver disease cited fatigue, and nearly one-third of patients cited sleep difficulties as contributing to their distress. Sleep difficulties have been regarded as one of the most distressing symptoms for adolescents with LTs, and they have previously been negatively correlated with quality of life in this population. Given that psychological interventions for sleep problems are highly effective, their implementation in young LT recipients warrants further consideration. Problems with school and/or employment were cited in almost one-third of young people. The potential interaction of these concerns should not be underestimated (sleeping problems and fatigue could interfere with school and work performance and lead to problems attaining work). These concerns should be preempted and taken seriously by clinicians within the routine clinic review, both to engage the young people in discussing their most pertinent concerns and to facilitate appropriate onward referrals.

Crucially, because most of the concerns raised (including anxiety and depression) are amenable to intervention, this could dramatically improve patient care and optimize young people’s health, well-being, and educational/occupational outcomes. Psychosocial distress has been correlated with nonadherence in both adolescents and young people, and addressing these issues is likely to also have a positive impact on their physical health.

Self-Management Skills

As described, adolescence and young adulthood for LT recipients can be associated with poor health outcomes related to nonadherence and graft loss. During this time frame, patients begin to acquire self-management of their healthcare. From a behavioral perspective, one of the simplest explanations for difficulties during transition is that some young people are just not yet good at managing their own healthcare. The American Academy of Pediatrics stated that a well-planned transition “allows young people to optimize their ability to assume adult roles and functioning.” However, there are limited data to support this assertion and a need for studies implementing psychometrically sound measures of self-management to investigate the potential relationship between self-management and health outcomes.

Many CYP with liver diseases are diagnosed in infancy or childhood when their carers are responsible for these tasks. The role of CYP and their carers in this setting changes significantly during young adulthood, along with the expectations of clinicians. There is a drive toward independence, with carers gradually stepping back and peers becoming more important. For example, clinicians will direct questions and advice toward CYP themselves and may see them individually for their consultation. However, with the delayed timing of role transitions in today’s society, such as completion of education, marriage, and parenthood, the CYP may continue to rely on parental support well into the period of young adulthood. This may be especially true in our population of CYP, considering almost 50% of children post-LT require special educational support. Our CYP may be more likely to struggle with the development of the appropriate skills to manage their condition during adolescence and may continue to rely on carer support. Indeed, most CYP with childhood liver disease have a long history with pediatric care providers, with many relationships starting in infancy. Transition of healthcare to adult services can therefore be just as challenging for carers themselves, who have their own relationships with clinicians and healthcare providers.

Failure to develop self-management skills appropriately is perceived as a major barrier to transition by adult health professionals, and it is assumed that better self-management skills in young people correlate with better health outcomes, despite the lack of empirical data. A national US survey of adult transplant physicians assessed characteristics of transferred patients as well as the transition process itself. A large percentage (30.8%) of young people were perceived to have been transitioned with inadequate knowledge of their condition, which the authors argued identified the need for more integration of the adult side when we are developing tools and approaches to assess transition readiness. Furthermore, in young people with LTs, Annunziato et al. found that self-management skills did increase with age during transition; however, although improved relative to their adolescent counterparts, young adult patients did not appear to be comprehensively managing their care. Later work by the same team found that when patients endorse more responsibility for their care, clinical outcomes were in fact worse, indicating that indiscriminate promotion of self-management by adolescents may not be advisable. Given that executive functioning skills develop toward the end of young adulthood (rather than soon after an individual’s 18th birthday), clinician expectations around the adolescent’s ability to self-manage may need to be adjusted in this developmental period. In practice, many patients may physically transfer from receiving services at pediatric to adult-oriented facilities before they manage the requirements of their particular medical illness. It is important that self-management is viewed as a process rather than a one-off conversation, especially in patients with additional learning needs (found at an elevated rate in our patients). It is recommended that clinicians periodically assess developmentally appropriate skills of health management to understand patient education needs and their skill acquisition over time.

In the past few years, different strategies for assessing self-management among transplant recipients have been developed. These involve measuring “allocation of responsibility” of healthcare management tasks (i.e., how these are divided between patients and their caregivers) or measuring the “level” of healthcare management skills obtained by the patient. As yet, there is currently no widely available validated tool for the assessment of self-management. The team at King’s has further adapted a brief, validated tool to reliably measure CYP’s self-management skills and highlight specific areas of need or gaps in knowledge (to focus on education in appointments). The questionnaire has been adapted for use in the UK transplant and chronic liver disease population, with the input of patients and colleagues. In a sample of 47 young people (the majority being > 18 years of age), less than half reported consistently managing their liver disease independently. None of the behaviors assessed were considered to be effectively mastered by the whole cohort. Levels of mastery of healthcare management reported were broadly comparable to US peers. However, there were some differences; for example, our UK sample reported greater mastery of appointment scheduling and discussion of management plans with parents/healthcare providers but less mastery of medication taking, knowledge of medication, and engagement in a healthy lifestyle than their peers in the United States. Future work will investigate the relationship between self-management and mental health and develop interventions to support the transition to adulthood such that patients are better prepared before moving to adult healthcare.

This brings us to the final part of the chapter, where we will describe models of care for young people transitioning from pediatric to adult healthcare settings and illustrate the importance of multidisciplinary work, including peer support.

Multidisciplinary Support and Healthcare Provision for Young People

Models of Healthcare Provision

It is estimated that young people currently make up 25% of the world population. Unfortunately, the majority of healthcare services are currently not organized to address the needs of this distinct population, and the timing of transition from pediatric to adult healthcare providers tends to be defined by actual age rather than when developmentally appropriate. In addition, there is no agreement worldwide as to what constitutes a successful outcome of the transition process among young people with special healthcare needs.

The differences between pediatric and adult healthcare services are significant, as illustrated in Table 46.1 . Together with developmental challenges of nonadherence and disengagement with health services prevalent in this population, this is likely to impact on the overall inferior outcome of this population, as illustrated previously. Healthcare providers should appreciate that healthcare transition entails more than handing over patients from one service to another and strive to provide developmentally appropriate care for young people irrespective of whether they are looked after in pediatric or adult services. Different models of service provision are possible and dependent on various factors such as location of pediatric and adult services (colocated or not), access to a multidisciplinary team of health professionals, adolescent inpatient facilities, patient load, and so on. Harden et al. demonstrated that the introduction of a young-adult program with targeted support for young people post–kidney transplant led to no graft loss compared with a historic cohort who did not receive this support.

Feb 23, 2021 | Posted by in HEPATOPANCREATOBILIARY | Comments Off on Challenges for Young People With Liver Disease Including Transition to Adult Services

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