Assessment and management of psychosocial challenges in pediatric liver transplantation

Abstract

Liver transplantation offers the potential of survival and acceptable quality of life1 to children and adolescents who might otherwise not be able to live. However, despite the dramatic improvement in patients' health as well as outlook, liver transplantation is not a complete cure. Rather, the patient is trading a life-threatening, sometimes acute illness for a chronic one. The transplant survivor faces many challenges that are faced by other survivors of chronic illnesses. Patients need to adhere to a medication regimen and clinic follow-up schedules. They need to avoid certain situations (for example, exposure to a person who has a viral illness). Moreover, they live under the constant threat of a rejection or, in some cases, a relapse of their disease. These issues are perhaps even more important in children than adults. Children are expected to spend a full life span with their transplants. Also, children, more so than adults, face challenges related to the achievement of developmental tasks such as peer socialization and cognitive competency. There is a vast literature related to the challenges facing chronically ill children, and it would be impossible to summarize it here. It would also not be especially original, as excellent texts already exist on the subject of pediatric adjustment to medical illness.2-4 Rather than providing a generic review of psychosocial challenges, I have decided therefore to describe the ones that are fairly specific to the transplant situation. Psychosocial assessment in medically ill children is challenging because medical symptoms such as fatigue might be misinterpreted by the assessor as psychiatric.5, 6 Conversely, psychiatric symptoms might be misconstrued as physical and thus not adequately addressed.6 The mental health professional who assesses the transplant recipient might not be particularly knowledgeable about the normal and expected course of recovery of transplant survivors. To address this issue, transplant centers have moved to create either specific affinities or actual positions for mental health providers. These providers become familiar with the transplant situation. This is similar to what happens with other consultants (for example, an infectious disease specialist) that participate in transplant team activities and develop an expertise that is of particular value to the transplant team.7 Although it is preferable to use the expertise of a mental health professional who is embedded within a transplant service, 1 study found that familiarity with the medical illness may not always be necessary. The performance of general psychosocial screening measures in assessing medically ill children (many of whom were liver transplant recipients) may be adequate.8 Furthermore, interviews by mental health professionals who are not particularly familiar with a child's medical illness closely correlated, in that study, with evaluations done by a team of professionals including the treating physician.8 Thus, in cases in which a dedicated mental health professional is not available to the transplant team, data suggest that an assessment of mental health symptoms can also be successfully accomplished by an alternative scheme. If it is impossible to embed a mental health professional within the service, programs might use questionnaires administered by transplant team clinicians coupled with a judicious use of consulting, unaffiliated mental health clinicians (for example, the mental health consult service). The child's report of his or her own symptoms should always be sought independently of the parent's report. This is because a parent's descriptions of his or her child's mental health symptoms are dependent, to some extent, on the parent's own emotions.9 In the transplant setting, adults tend to either underestimate10 or overestimate11 the child's mental health symptoms. This is probably because adults tend to focus their thinking on prognosis much more than children. Thus, a transplant can be perceived as a cure, or at least as a hope for a brighter future, by adults. It can also, conversely, be perceived as an ongoing health risk. In contrast, depending on their particular situation, children may concentrate on the immediate improvement in their symptoms post-transplant or on the limitations and sometimes pain and disability that they might experience after a transplant. Thus, there are significant differences between the parent's report of the child's symptoms and the child's own report. These differences depend on the clinical picture and the parent's own coping style. Although parents may either underestimate or overestimate the child's adjustment difficulties, transplant clinicians generally underestimate them.10 Therefore, the child's own report should always be sought if possible. Discrepancies between parent and child reports of the child's symptoms can help the clinician understand the parent's adjustment to the child's illness and needs. In summary, children who have a liver transplant face challenges similar to those faced by children with chronic medical conditions. Parents and clinicians tend to misjudge the child's adjustment difficulties. This suggests that clinicians should not exclusively rely on parental reports (although the parent's report should also be sought) and should not overly trust their own clinical judgment on the matter. Psychosocial assessments should therefore be performed as a matter of routine in the transplant center, rather than being confined to suspected cases. Efforts to integrate mental health workers into the transplant team are expected to improve the team's ability to detect mental health problems and adjustment needs in recipients. However, empirical data do suggest that even in the absence of specific knowledge about the illness, mental health professionals as well as standard screening instruments perform well. These can and should be used if a dedicated mental health professional is not available. The role of the pretransplant assessment in children is to identify potential risks that would make the posttransplant adjustment period more challenging to the patient and his or her family. The hope is that if clinicians identify these risks early, they can intervene vigorously and improve the child's quality of life and posttransplant outcome. Unlike in adult recipients, data are lacking about what psychosocial risks would make it impossible to transplant a child because they pose a great danger for subsequent organ failure. In addition, pediatricians typically allow children the benefit of the doubt and hold the parent, rather than the child, responsible for the child's behavior (this may also be the legal stand). Thus, the prospective child recipient's behavior or circumstances, as opposed to an adult's behavior or circumstances, are rarely considered grounds for withholding transplantation. Therefore, the pretransplant psychosocial assessment in children is not focused on establishing whether or not the recipient is a suitable candidate. Only in very extreme circumstances should a pretransplant psychosocial assessment lead to a determination that the child should not receive a transplant. The transplant setting offers a unique opportunity to engage in preventative treatments in cases in which a risk is identified before the distressing event (a transplant) has happened. Although there is hardly any consensus about what a psychosocial pretransplant assessment should include, several risk categories are typically assessed.12-17 These might include frank psychopathology (for example, depression and anxiety disorders), family and social functioning and circumstances, adherence to the medical regimen, and general distress. It has never been demonstrated that pretransplant psychosocial assessments actually lead to improved posttransplant outcomes in children. Furthermore, in adults, posttransplant psychosocial factors, more than pretransplant factors, are associated with poor outcomes.18 Thus, there is no reason to focus only on performing pretransplant assessments—posttransplant assessments are at least as valuable. The compelling reason to implement these assessments as routine practice is that there have been numerous studies19-23 which have demonstrated that psychosocial risks are associated with poor posttransplant medical outcomes. If all published studies about psychosocial risks in solid organ transplant recipients (children and adults) are considered, the risks include a dizzying array of factors, which are summarized elsewhere.24-29 However, much of the literature is based on studies in adults, and some risks in adults are far less important in young children (for example, alcohol abuse and personality traits). Also, much of the literature consists of small studies that are not targeted. Studies that are not hypothesis-driven (for example, rather than investigating 1 risk factor prospectively, they look at the psychosocial profile of recipients or look at a large number of predictors) suffer from a high likelihood of spurious results. In children who have had a liver transplant, the only psychosocial risk factor that has been shown to be predictive of poor medical outcomes in a prospective, targeted study is a history of child abuse.23 Other candidate predictors in this particular population are posttraumatic stress disorder (PTSD) and depression.30, 31 Posttraumatic stress and depression have been shown to be predictive of poor outcomes in prospective studies in adult recipients.21 Somewhat unique to pediatric recipients is the need to assess the family, particularly the parents, as well. Below, I address these unique, evidence-based aspects of the assessment only (posttraumatic stress and distress, depression, a history of abuse, and family assessment). I also comment briefly on management strategies in cases in which these risks are identified. It is reasonable to assume that many and probably most transplant recipients and their parents are distressed20, 32-34 following transplantation and perhaps even more so before the transplant. PTSD is different from general distress in that it is a diagnosable psychiatric disorder for which there are diagnostic criteria as well as proven treatments.35, 36 In contrast, distress is a less precisely defined concept. Posttraumatic stress symptoms are associated with mortality in at least 1 transplant setting21 and with poor adherence in children with liver disease, including transplant recipients.22, 31 The hallmarks of posttraumatic symptoms are a heightened level of distress and hypervigilance, avoidance of stressful situations that might lead to avoidance of medication-taking and nonadherence,37 and re-experiencing of the traumatic event. Fortunately, PTSD is treatable,38 and so it is important to identify it. The first-line treatment of PTSD children includes cognitive-behavioral therapy38; selective serotonin reuptake inhibitors have been shown to be effective for the treatment of PTSD in adults.39 Children with PTSD may or may not have associated behavioral problems, and therefore some of them may not present as a management problem at first. Children might present as shy, avoidant, hostile, vigilant, and reluctant to communicate with the provider. These symptoms should raise a red flag in clinicians in the transplant setting and should trigger further evaluation. A rating scale may be used to screen for posttraumatic stress symptoms. Resources related to the identification of posttraumatic stress in children who are medically ill are readily available through the Web site of the National Child Traumatic Stress Network, which maintains a section dedicated to medical traumatic stress in children.40 With respect to general distress, it is expected to be common before and after transplantation, and whether or not further evaluation is indicated would depend on its severity and associated features. Both distress and posttraumatic stress are harder to diagnose and treat in very young children, but they are treatable in children. Alleviation of distress does not necessarily require a mental health professional—transplant team clinicians can engage in providing comforting information, suggesting community resources, and facilitating an open discussion of distressing events in the clinic. In contrast, the treatment of PTSD should be administered by a mental health professional and should not be attempted by providers who have no formal training in mental health. Depressive disorders have been shown to predict poor posttransplant outcomes in targeted21 and cross-sectional30 studies. Depression is also one of the best studied risk factors for poor physical outcomes in a variety of disease categories.41, 42 Depression is treatable in children43 through the use of either psychotherapy or psychopharmacotherapy, and therefore it is important to identify and address it. Although providers might be more familiar with the presentation of depression in comparison with the other risks described in this article, it is important to distinguish between normative sadness or distress and actual depressive disorders. The distinction is sometimes hard to make, and in cases of doubt, a consultation with a mental health professional might be useful. It hinges on the pervasiveness of sadness (is sadness present most of the time or all of the time for more than a few days?), the presence of anhedonia (an inability to enjoy activities that the child can engage in currently and has previously enjoyed), and associated features such as irritability and sleep and appetite problems (either too much or too little). There are standard assessment tools for depression. One example is the Children's Depression Inventory, which is available for a fee.44 It has been used successfully in medically ill children.8 Depression in very young children is more difficult to diagnose, and there are far fewer data about its treatment in very young age groups, but depression is treatable in children. The treatment of depression should be supervised by a mental health professional. A history of physical abuse (but, interestingly, not of domestic violence) has been shown to be associated with poor posttransplant outcomes in pediatric liver transplant recipients in a cross-sectional study.30 A subsequent prospective study confirmed those earlier results,23 making child abuse the only psychosocial risk to date that has been shown to predict poor posttransplant outcomes in a targeted, prospective study in this population. Because it is the most rigorously studied risk factor and because the effect on outcome is substantial, it should not be missed. Abuse can interfere with the child's care in many ways. These include a lack of a supportive environment at home and a child's lack of trusting relationships with adults and authority figures (and, therefore, failure to follow medical recommendations). To address this risk effectively, the transplant team should first be alert to the possibility of abuse in candidates and recipients and, if it is possible, avert it. However, this is rarely possible. When abuse is known to have occurred already, supportive measures could be indicated. These include the involvement of child protective services (if the abuse situation is suspected to be ongoing), closer monitoring of the child and the family, and treatment of emotional consequences of the abuse. The abused child might present with physical stigmata and emotional or behavioral problems or might not appear any different from other children. There are no hallmark features that will be present in every abused child. Therefore, there is a compelling reason to screen for abuse. This could be done through the use of targeted questions, which were sufficient to identify abuse histories in previous studies.23, 30 Specific questionnaires such as the Trauma Symptom Checklist for Children can also be used for this purpose45 and may offer the advantage of more likely disclosure (if the child is ashamed to openly talk about the experience). Once abuse is identified or suspected, the clinician is required to establish that the patient is safe and report the event in accordance with local and federal law. An immediate referral to a mental health professional is indicated in my view. I also recommend enhanced disease and emotional monitoring in all identified cases, even long after the abuse itself has stopped. This monitoring is indicated because abuse is associated with a myriad of long-term physical and emotional sequelae post-transplant,23 including elevated liver function tests, elevated risk of rejection, and nonadherence. Family functioning in pediatric liver transplant recipients compares favorably with published norms.1 Hence, it would be incorrect to assume that families of transplant recipients are dysfunctional. However, in those families that do malfunction because of parental distress, child psychopathology, social circumstances, lack of support, or any other reason, the risk to the child is substantial.34, 46 Therefore, it is important to assess the degree to which the family can provide support to the child recipient. This might include a family system assessment, typically done through the use of a questionnaire as a first step, and/or a detailed family assessment or a separate psychosocial assessment of the parents. It is not clear what kind of assessment is best suited for the parents, but assessment of parental distress, depression, and demographic and social variables might be indicated. Family system interventions have not been rigorously studied in transplanted children, but they have been helpful in other medically ill children.47, 48 Overly distressed or depressed parents might present in the same way in which adults who are anxious or depressed present in general care settings. However, parents might strive to look strong in front of a child or in front of the child's medical team. The focus should be on not only the parent's distress but also the degree to which the illness impacts the family structure and organization or the ability of the family to support the child. Thus, it may be helpful to ask the parent a few open-ended questions in a direct manner without the child's presence. For example, a clinician might ask the parent how he or she is coping, who is available to help, and how the transplant team can facilitate the parent's care of the child. Because distress and posttraumatic stress are common in parents of medically ill children,9 it might make sense to screen for them as well as depression. Questionnaires that tap into these domains, such as the Beck Depression Inventory49 and the Impact of Event Scale,50 are readily available. However, a lack of clear data about the utility of such screening in the transplant setting makes it impossible to recommend it as routine practice at this point. When transplant team members suspect that a parent is suffering from a mental health disorder or is disabled by mental health symptoms such as distress or dysphoria, a referral is indicated. Pediatric transplant team members and their affiliated mental health providers should not attempt to provide mental health treatment to the parent. This is because of the potential conflict between the treatment of the parent and the treatment of the child. The child, not the parent, is the identified patient of the pediatric transplant team. With respect to family functioning, there are questionnaires that specifically assess family functions, such as the Family Assessment Device (FAD), which is available on the web.51 The FAD has been successfully used in the transplant setting.1 However, most of the family system assessment questionnaires tap into domains that are not easily translatable into the provision of specific treatment options, and some are hard to interpret and score. Because of this and because family dysfunction is not more common in the pediatric liver transplant setting than in the general population,1 I do not recommend the routine use of family assessment screens by medical providers. Instead, family structure assessment should be performed by a mental health professional as a response to a specific concern raised by a provider. In summary, psychosocial assessments before or after transplantation in children cannot be recommended as evidence-based efforts to improve posttransplant outcomes until data establish that these assessments lead to interventions that in fact improve outcomes. Nevertheless, assessments can identify risk. If this identification leads to an attempt to modify the risk, psychosocial assessments can be advocated as potentially positive additions to routine patient care. The psychosocial risks that are discussed here are those that are, in my opinion, of particular interest in children who receive liver transplantation. However, there are certainly other risks. To help clinicians understand the general risk categories that might come into play, I suggest the biopsychosocial model to guide one's thinking. Biological risks include the specific reason for the transplant, genetic factors that may determine transplantation risks as well as mental health risks, and pretransplant biological indices. These of course can interact with other risks. Psychiatric/psychological risks include those that are related to the recipient, such as depression and PTSD. Social risks include the interaction of the child with the environment. This involves, most importantly, the parents. Social factors also involve economic factors, peer group interactions, interactions with other important caretakers, and the function of the transplant team in relation to the child. When faced with a particular patient, a clinician might start with the most well-documented and specific risks, some of which are described here. As needed, a broader assessment will be aided by the clinician addressing domains that are included in the biopsychosocial model. FAD, Family Assessment Device; PTSD, posttraumatic stress disorder. Studies have repeatedly shown that in children, almost all rejection episodes 6 months or more after liver transplantation are attributable to nonadherence to immunosuppressant medications.52-55 Thus, nonadherence is the most important risk factor for rejection episodes in long-term survivors of pediatric liver transplantation. Nonadherence is common,52-57 and this risk is potentially modifiable.58, 59 Therefore, emphasis should be given to identifying and addressing nonadherence in pediatric transplant settings. How does one know whether a patient is taking the medication or not? Simply asking is apparently not enough. Self-reports, parent reports, or clinician reports of adherence are not related to outcomes and are not correlated with objective measures of adherence in children who have had a liver transplant.54 Therefore, an objective measure needs to be incorporated into the assessment. Electronic monitors are pill boxes with electronic chips that record every time that a pill box is opened. Although frequently used in research, electronic monitors are not particularly suitable, at this point, for clinical practice. Problems include the inability to monitor liquid medications, patients' reluctance to use these devices,31, 60 cost, and the need for dedicated personnel and software to download and interpret the data. Nevertheless, it is conceivable that better devices and better interfaces will make electronic monitoring more valuable in the future. Another method that has been successfully used to monitor adherence in children who have had a liver transplant uses clinic attendance rates.34 This method incorporates readily available data (clinic attendance records) and thus is easy to use. However, having attended a visit does not necessarily equal having taken a medication. Other objective methods include pill counts and prescription refill reports.61 Finally, a method that is uniquely suited to the transplant setting involves the calculation of the degree of fluctuation between immunosuppressant blood levels, which are obtained in routine visits. This method also uses data that are clinically available in the transplant setting; it is the best studied measure of adherence in pediatric liver transplant settings.52-55 It has been shown to correlate with rejection outcomes in 3 transplant centers52-55 and with other objective measures of adherence.31 It has the benefit of being both an objective measure61 and a direct measure.62 All of these methods still need to be validated in larger, multicenter trials before they can be recommended as evidence-based for clinical use. At this point, practitioners should choose between those objective measures based on the specific setup in each center and the degree of nonadherence risk. I posit that the single most important challenge to improving adherence in the transplant setting is the identification of nonadherence. Once it has been established that a patient is, indeed, not taking the medications as prescribed, the rest of the management is relatively straightforward (if not always successful). First, a detailed explanation of the importance of adherence as well as increased monitoring of the particular child should be attempted. Doing only that may be enough in many cases—this approach seemed to improve adherence substantially in 1 naturalistic, uncontrolled pilot study.59 Second, an evaluation of psychosocial risks might commence, and those risks (for example, depression) should be addressed. Third, a similar evaluation of the family and the parents might be advisable. Fourth, it may be helpful to consider factors related to the medication regimen (for example, switch to a medication that has fewer side effects or switch the frequency of medication-taking). It might also be helpful to consider the patient's interface with the treatment team (for example, replace the providers if a good rapport has not been established). Unfortunately, there is not even 1 adequately powered, prospective, randomized, blinded, controlled trial of a treatment of nonadherence in children who have had a solid organ transplant. Because the concept of adherence is quite different in adults and children (different risk factors and different roles of social supports and family), adult literature can provide little guidance in this area. Thus, at this point, no intervention can be recommended as evidence-based. Just as for many other behaviors, a developmental perspective is important when adherence is considered. When the child is very young, medications are being administered by a parent, and the parent's adherence is the important factor. Later, the child assumes increasing responsibility over his or her own care. The shift in responsibility is associated with decreased adherence.63 It has been estimated that most of the transition in medication-taking responsibilities happens between the ages of 9 and 16 in children who have had a liver transplant.54 However, the process might be far longer than that. The shift in responsibility can be evaluated with specific measures of transition.64 It is probably possible to affect this process positively by a combination of education and cognitive-behavioral approaches.58 Providers should be aware of the transition in responsibility and react to it in the following ways. First, assess it (ask who is responsible for disease management). Second, acknowledge that this process might be difficult for the parent and child. Third, as the child gets older, address him or her increasingly as the primary point of contact and as a valued decision maker in his or her own care. Fourth, employ standard measures or detailed interviews to assess the adequacy of this process either in all adolescent patients or at least in those that are considered to be at risk. Fifth, target this process for additional exploration with the patient as needed.58 Psychosocial risks and, in particular, nonadherence are associated with poor posttransplant outcomes. Psychosocial risks as well as nonadherence may be under-recognized by parents and providers. Therefore, it is important to assess them as a matter of routine rather than to rely on clinical judgment or parent reports alone. The assessment should be developmentally sensitive. Children at different developmental stages face substantially different tasks, including different expectations about disease management. Psychosocial risks can be reliably measured with appropriate validated questionnaires, tests, or interviews. Attempts should be made to address them through the judicious use of transplant clinic personnel as well as mental health providers. Targeted, prospective, multicenter treatment studies are lacking: they would put to rest the question mark that must presently accompany many recommendations in this area. For now, I have attempted to summarize a few general ideas that might be helpful to the practitioner in understanding the role and content of the psychosocial assessment (Table 1). Table 2 summarizes a few points that might be helpful in implementing clinical protocols that target the assessment and treatment of nonadherence.