Adult provider role in transition of care for young adult pediatric recipients of liver transplant: An expert position statement

Abstract

Health care transition (HCT) is the process of changing from a pediatric to an adult model of care. Young adult pediatric recipients of liver transplant transferring from pediatric to adult health care services are highly vulnerable and subject to poor long-term outcomes. Barriers to successful transition are multifaceted. A comprehensive HCT program should be initiated early in pediatrics and continued throughout young adulthood, even after transfer of care has been completed. It is critical that pediatric and adult liver transplant providers establish a partnership to optimize care for these patients. Adult providers must recognize the importance of HCT and the need to continue the transition process following transfer. While this continued focus on HCT is essential, current literature has primarily offered guidance for pediatric providers. This position paper outlines a framework with a sample set of tools for the implementation of a standardized, multidisciplinary approach to HCT for adult transplant providers utilizing “The Six Core Elements of HCT.” To implement more effective strategies and work to improve long-term outcomes for young adult patients undergoing liver transplant, HCT must be mandated as a routine part of posttransplant care. Increased advocacy efforts with the additional backing and support of governing organizations are required to help facilitate these practices.

INTRODUCTION

Improvements in pediatric liver transplantation (LT) have led to more patients reaching young adulthood. Young adult (YA) recipients of LT transferring from pediatric to adult models of care have increased episodes of rejection, graft loss, and medical complications. Rates of patient mortality and graft loss approach 30% following transfer of care. ¹ Successful transition ensures that youth acquire independent health care skills, prepare for an adult model of care, and successfully transfer to new providers without disruption in treatment. This necessitates a multidisciplinary approach to transition planning, which is a labor and resource-intensive undertaking. Adult providers may not be as adept at caring for YAs and may lack the requisite experience to effectively manage these patients.

The federally funded national resource center on transition (Got Transition) developed “The Six Core Elements of Transition.” These core elements define a sequential clinical process with a sample set of tools for pediatric and adult practices. Quality improvement using the Six Core Elements of Health Care Transition (HCT) has resulted in the development of a systematic clinical transition process in adult academic primary care practices. ² The incorporation of these core elements is not routinely performed by adult LT clinics that care for pediatric recipients of transplant. Implementation of this system may improve the delivery of transition services for this population and result in important long-term gains in patient-centered outcomes.

A recent position statement from the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) highlights the importance of early initiation of transition efforts by pediatric providers. ³ This allows for a developmentally appropriate, individualized approach to care. This document also endorses the use of the Six Core Elements of Health Care Transition as being applicable to adolescent and YA recipients of LT and supports the establishment of multidisciplinary HCT programs in LT. A comprehensive discussion and review of the pediatric provider’s role and approach to HCT is beyond the scope of the paper.

This manuscript is a work product of the American Society of Transplantation’s (AST) Liver and Intestinal Community of Practice (LICOP). To date, there has been no formal position statement from the AST acknowledging the importance of HCT for YAs while offering a toolkit for adult providers to accept pediatric patients undergoing LT. This document seeks to offer pragmatic guidance for adult transplant providers on how to build a multidisciplinary transition program utilizing the “Six Core Elements of Transition” to enhance care for pediatric recipients of LT thereby seeking to lower rates of rejection and graft loss and improve clinical outcomes.

METHODS

In discussion with members of the AST LICOP, it was deemed necessary to provide a guiding document outlining the adult provider’s role in the transition of care for YA pediatric recipients of LT. A multidisciplinary working group with expertise in HCT was formed. Members included both pediatric and adult hepatologists, advanced practice providers, a transplant surgeon, a pharmacist, and a neuropsychologist caring for patients who had undergone pediatric LT. Relevant literature was reviewed using PubMed/MEDLINE/Google Scholar databases applying the following terms: HCT, transition of care, transfer of care, pediatric liver disease, pediatric LT, adherence, transition readiness, emerging adulthood, adolescence and young adulthood, quality of life (QoL), reproduction, transplant outcomes, and retransplantation. Literature searches were conducted through June 2023. Non-English literature was excluded. Sections were completed by individual authors with review and editing of each draft by the coauthors. The available literature and expert opinion were used by the authors to formulate suggested guidance for each section. These recommendations were modified and agreed upon by the multidisciplinary HCT working group members through virtual meetings and electronic communications. A formal grading method was not used.

BARRIERS TO CARE

Developmental considerations of emerging adulthood

Neurocognitive deficits and executive dysfunction are prevalent in YAs who have undergone LT. Executive function is responsible for planning, organization, working memory, flexibility, evaluation of risk and reward, and the capacity to dissociate decision-making and strong emotion (Figure 1). ⁴ In a longitudinal, multicenter study of the developmental course of pediatric recipients of LT, patients demonstrated higher-than-expected rates of below-average intellectual functioning, math weaknesses, and executive functioning deficits following transplantation. Fourteen percent of the sample also met the criteria for a diagnosis of attention deficit hyperactivity disorder. These deficits persisted over time despite posttransplant recovery. Lower intellectual functioning was correlated with pretransplant markers of nutritional status and operative complications. ⁵ Other contributing factors may include missed school days and the impact of chronic immunosuppression on neurocognitive development. It is important to consider intellectual, adaptive, functional academic (eg, math skills), and executive deficits as barriers to HCT as these may contribute to a YAs’ poor understanding of their illness, the transition process, and nonadherence. In addition, many transition-age youth may not have received appropriate services for these developmental concerns, including the need for documentation of guardianship for youth with developmental and intellectual disabilities. It is recommended that neurocognitive status is screened and appropriate interventions or accommodations are included as part of the transition planning process.

FIGURE 1.

Summary of multifaceted barriers to health care transition.

Mental health

Many psychiatric issues may present in adolescence and correspond with the timing of HCT. Adolescents and YAs have a suicide rate nearly triple that of younger adolescents. ⁶ The additive burden of living with a chronic health condition such as LT can also lead to increased emotional difficulties and poor QoL. In a study of 741 children between the ages of 3 and 12 who underwent living donor transplantation, recipients were more likely to have mental health conditions when compared to healthy peers. ⁷ In another study of patients who had undergone LT during YA, 18% of participants screened positive for anxiety and/or depression, which was significantly higher than the prevalence noted in the general YA population. ⁸ There is also an increased prevalence of posttraumatic stress disorder in young people who have undergone a transplant. ⁹ These increased psychosocial concerns are often associated with decreased QoL, decreased adherence, and poor medical outcomes. It is essential to screen for and to treat mental health conditions throughout the HCT process. The inclusion of mental health professional support embedded within the transplant team is critical.

Substance use and substance use disorders

Substance use and substance use disorder peaks for transition-age youth. ⁶ The burden of a serious health condition is an additional stress in this high-risk population. In a meta-analysis of substance use among pediatric and YA recipients of transplant, rates were similar to nontransplant peers and may lead to poorer outcomes. ¹⁰ In adults, pretransplant substance use is strongly associated with posttransplant nonadherence to substance use restrictions ¹¹ and greater postoperative complications, increased risk for hospitalizations, and diminished QoL. ¹² The need for a clear, directive policy regarding substance use, standard evaluation, and early intervention is supported by transplant providers. ¹³ Providers should include an assessment of substance use, such as the Alcohol Use Disorders Identification Test-Concise (AUDIT-C), ¹⁴ as part of transition readiness evaluations.

Health literacy

Sufficient data are lacking from pediatric LT regarding the impact of poor health literacy (HL) on successful transition of care outcomes. A recent study of pediatric recipients of LT, however, found that limited HL was identified in 57% of recipients and 47% of caregivers. Patients with limited HL were more likely to be younger in age, Hispanic, and less likely to have obtained a high school diploma or equivalent. This study also demonstrated that limited HL was associated with decreased measures of transition readiness. ¹⁵ Inadequate HL may be an unrecognized barrier to a successful HCT.

Data from other pediatric chronic illnesses also suggest that HL may be an important predictor of successful transition of care. In one study of adolescents with special health care conditions, the authors found that poor HL was associated with lower transition readiness scores and increased risk of Emergency Department visits for conditions that could be addressed by primary care providers (eg, asthma exacerbations). ¹⁶ In another study of pediatric patients with inflammatory bowel disease, the authors concluded that only 36% of patients >18 years of age had adequate HL. Moreover, when clinicians were asked to globally assess their patients’ HL they overestimated—deeming 47% of their patients to have adequate HL. ¹⁷

Given the evidence from other pediatric chronic illnesses on HL in the transition of care, transplant teams may consider screening patients for HL. The Newest Vital Sign is a quick, freely available tool that requires patients to read and interpret a nutrition label. ¹⁸ Limitations in HL may be mitigated by employing modified communication strategies regularly during visits, thereby improving provider communication and individualized patient and caregiver education. Additional practices may include print materials, longer duration, and more frequent clinic visits, and increased access to clinical coordinators and social workers.

Social determinants of health

The social determinants of health are important contributors to health outcomes in pediatric chronic illness. Social risks, such as neighborhood socioeconomic deprivation, have been associated with adverse long-term pediatric LT outcomes.^19,20 In one single-center study of pediatric recipients of LT, the authors found that Black children had a striking 44% mortality rate in the 10 years following transfer of care to an adult provider, compared to 25% of White children. ²¹ These preliminary data demand that we further identify underlying social risks that contribute to these disparities and develop interventions around these risks.

Future studies should evaluate the impact of material economic hardship (eg, food insecurity), HL, and financial strain on transition of care outcomes. ²² Further, in-depth qualitative interviews and observations may uncover contributors to poor transition outcomes for high-risk children. ²³ Interventions may include the use of patient navigators to help patients traverse new health care systems, advocate for their needs with adult transplant providers, and provide coaching as these YAs transition their care.

System-level barriers—Reimbursement/cost, time

There are system-level barriers to the transition of care that warrant future policy-level studies and interventions. A recent survey of adult LT providers cited a lack of sufficient time and staffing as major barriers to HCT and the ability to accept pediatric recipients of LT into the adult practice. ²⁴ Other notable barriers included patient willingness to participate, lack of familiarity with caring for recipients with congenital disease, and insurance concerns. Transplant centers receive most of their revenue from transplant surgery. Further, 1-year outcomes are closely monitored for transplant programs, and if these outcomes suffer, transplant programs can lose accreditation. These factors may contribute to transplant programs prioritizing the performance of LTs and ensuring 1-year patient survival. Conversely, this leaves little financial incentive for adult transplant programs to prioritize the acceptance of pediatric patients. Moreover, a successful transition requires multidisciplinary care—a resource-intensive process. Thus, future advocacy should be aimed at revising and incentivizing reimbursement models for the transition of care. A transition of care–specific ICD-10 code (Z71.87) recently became effective and may assist in reimbursing centers for their time and investment, thereby prompting the development of more robust HCT programs. Widespread implementation will require additional assistance and endorsement from governing organizations at both the national and international levels.

Best practice recommendations and summary

1. YA recipients of LT should undergo routine evaluation of neurocognitive function and screening for mental health conditions and risk-taking behaviors.

2. Routine assessment of HL may help guide intervention efforts, decrease barriers to adherence, and promote developmentally appropriate levels of treatment responsibility.

3. Future studies should evaluate the impact of HL, financial strain, and economic hardship on transition of care outcomes.

4. HCT is a time and resource-intensive process that lacks the necessary support and reimbursement necessary for widespread implementation.

THE 6 CORE ELEMENTS OF TRANSITION: EXTENDING TRANSITION INTO ADULT CARE

The approach to HCT in pediatric LT varies by center, underscoring the need for a standardized and comprehensive approach. A recent position statement from NASPGHAN endorses The Six Core Elements of Health Care Transition as being applicable to adolescent and YA recipients of LT and supports the establishment of HCT programs in LT. ³ A valuable resource for HCT program development is Got Transition, a federally funded national resource center on HCT and a program of The National Alliance to Advance Adolescent Health (https://www.gottransition.org/). A customizable toolkit of resources that focuses on The Six Core Elements of Healthcare Transition provides a framework to guide HCT program development.

As pediatric multidisciplinary LT teams progress in transition planning with YAs, early and ongoing collaboration with adult providers during the transition process is essential to maintain or improve outcomes and decrease late-onset comorbidities.^3,25,26 Extending the transition into the adult setting as the emerging adult solidifies skill acquisition and self-advocacy skills is imperative. A systematic review of youth with special health care needs reported statistically significant positive outcomes resulting from a structured HCT process. The review cited HCT activities related to transfer planning, transfer assistance, and integration into adult care as being important. ²⁷ The adult LT team is encouraged to continue HCT through an adaptation of the Six Core Elements of HCT as the YA achieves optimal self-management in their transplant care. In addition, education for all stakeholders within the adult team is essential to strengthen support of the program, understand the process, and reach a consensus regarding the approach to care for these emerging adults. It is important to note that transition program development requires significant time and effort, but specific aspects may be implemented as the larger infrastructure and resources are developed for a comprehensive program. The adapted Six Core Elements of HCT are presented with recommendations for implementation in the adult LT setting. ²⁸ Strategies are summarized in Table 1.

TABLE 1.

The six core elements: Integrating young adult liver transplant recipients into adult transplant healthcare

Core element	Strategies	Resources
I. Transition and care policy guide	• Adapt pediatric policy to adult health care practice. • Discuss the adult approach to care, privacy, and consent. • Discuss policy with YA at first visit	https://gottransition.org/6ce/?integrating-policy
II. Tracking and monitoring	• Decide on data to be tracked. • Create flowsheet through EMR, REDCap, or Excel. • Define responsibilities for data entry and review. • Confirm that the YA has established care with a PCP	https://gottransition.org/6ce/?integrating-flow-sheet https://www.gottransition.org/6ce/?integrating-registry
III. Orientation to adult practice	• Welcome packet or website with adult team information, contact numbers, and FAQs. • Define team members’ responsibilities for developing content, providing information, and tracking completion	https://www.gottransition.org/6ce/?integrating-welcome-orientation https://gottransition.org/resource/?sample-welcome-Atrium
IV. Integration into adult practice	• Review the transfer package, including medical summary, TRA, and legal documents. • Conduct routine meetings with the pediatric team to review YAs in the queue for transfer (affiliated centers). • Make previsit contact with the YA (phone, email, text, portal, and Meet and Greet)	Telehealth Toolkit (gottransition.org)
V. Initial visit	• Clarify adult approach to care and privacy/consent. • Set expectations for adherence and methods of communication. • Address YA concerns regarding transfer of care and practice changes. • Conduct self-care skills assessment. • Collaborate with YA on the plan of care and future goals	https://gottransition.org/resource/?turning-18-english https://www.gottransition.org/6ce/?integrating-self-care-assessment Vittorio et al (2023), Table 4, pp. 96–97 3
VI. Ongoing care	• Provide information about transfer completion to the pediatric team. • Link YA to adult specialty care. • Build collaborative partnerships with PCP and specialists. • Seek feedback from the YA on their transition experience. • Send reminders for laboratory appointments and other required tests for at least one year	https://gottransition.org/6ce/?integrating-feedback-survey-young-adults

Abbreviations: EMR, electronic medical record; PCP, primary care physician; TRA, transition readiness assessment; YA, young adult.

Transition and policy care guide

Transition policy development is the first core element in building a transition program. A policy within the pediatric setting defines key components of the program for adolescents and YAs and their caregivers. Developing an adult policy for continued transition of care builds on the YA’s current skills while establishing goals for care in the adult setting. Policy development is also important from a systems perspective as staff collaborate on program goals and structure to reach a consensus on the approach to care for the YAs. Staff should also understand the role of each stakeholder: the YA, parent/caregiver, and adult care team. The policy should be introduced at the first adult visit as part of the welcoming process. It should concisely outline the patient-provider relationship as a partnership of care in the adult setting, the adult practice’s approach to transition, what the practice can offer to assist with ongoing learning, and the adult approach to privacy and consent.^28,29

Tracking and monitoring

The adult team is encouraged to develop a process to identify and track YAs, who are transitioning to an adult model of care by building a Transition Registry with a method to track patient progress through the core elements, including the event of transfer to adult providers. A specific flowsheet on adult transition interventions and goals can be developed through the electronic medical record, REDCap, or an Excel spreadsheet to track their improvement to goal achievement after transfer.

Orientation to adult practice

With newly acquired self-advocacy skills, the YA may require assistance in orienting to the adult setting and new providers. Got Transition recommends that adult teams establish a process to welcome and orient the YA into the adult practice, which may include a description of that practice, an annotated list of care providers and services, contact numbers, and FAQs about the practice. Materials created for adult patients who newly received a transplant can also be modified and shared with the YA new to the practice. This information may be presented as a welcome packet or available online.

Integration into adult practice

Integration into adult practice is the planning stage by the adult center in preparation for the transfer of care and the initial visit. During this transition stage, the pediatric team is responsible for ongoing care until the initial adult appointment is completed. The referral should be reviewed to ensure receipt of current medical information, including the transfer package, transition readiness assessments (TRAs), and legal documents, if applicable. Affiliated pediatric and adult centers may conduct routine transition meetings to assist with transfer preparation with both teams’ members. This discussion for the patients in queue for transfer may include a review of their progress in the transition process, plans for upcoming transfer appointments, active medical issues, the current plan of care, the TRA, and any psychosocial concerns that may impact successful transition and transfer. In a survey of approaches to HCT, most pediatric providers (89%) reported communicating with the accepting team before care transfer, while only 57% of adult providers endorsed routine communication with the pediatric team, and 19% reported meeting with the pediatric patient before transfer of care. ²⁴ A study of recipients of renal transplant showed that YAs’ confidence in HCT centered around awareness of both pediatric and adult teams having familiarity with the patient’s history and care before transfer to help optimize a smooth transition. ³⁰

Validated TRAs have been created for patients with chronic conditions and have been increasingly used by pediatric providers. These typically include the Transition Readiness Assessment Questionnaire (TRAQ), ³¹ the UNC STARx Questionnaire, ³² or the Got Transition Readiness Assessment for Youth. ²⁸ These tools are frequently cited in the transplant transition literature, though they are not specific to LT. Transition templates have also been developed through the AST that can be adapted to the needs and population of individual transplant centers (https://www.myast.org/education/specialty-resources/peds-transition).

It can be helpful to make previsit contact with the YA by phone, email, text, or portal messages to welcome them to the adult practice and remind them of scheduled appointments. Some centers arrange a virtual “Meet and Greet” with the YA, caregiver, pediatric, and adult providers before the first adult appointment. This allows the YA to meet members of the adult team and ask questions about transfer of care, confirm upcoming appointments, and provide information on clinic location. YAs report fear and uncertainty as barriers to transition. Meeting the adult provider before transfer and knowing what to expect were cited as helpful by YAs in facilitating the transfer process. ³³

Initial visits

The initial visit should be scheduled within an appropriate time, ideally within 3 months of the last pediatric appointment. In a single-center study of 31 patients with chronic liver disease and/or LT who transferred to adult care, 47% of patients were seen within 2–6 months, and 20% were not seen for 6–12 months following their last pediatric appointment. The Emergency Department was the point of first contact with adult services for 20% of patients, and 19% reported being out of medications during the transition. ³⁴

The transfer package and final pediatric TRA should be reviewed before the first appointment. If center resources permit, a multidisciplinary approach to the transfer of care should be used to successfully integrate the YA into the adult health care system. Having the YA meet with a social worker, financial coordinator, and pharmacist during the initial visit can be helpful to ensure that the YA has appropriate resources within the adult care team. This team may also include a nutritionist and psychologist, depending on the YA’s needs. According to a recent survey of adult LT centers, pediatric recipients of LT are typically transferred to any provider in the adult practice (69.6%) rather than a designated hepatologist. ²⁴ Consequently, it is important to educate all team members about each center’s transition practice and methods to ensure continuity of care with a consistent approach as the YA-adult provider partnership is formed.

The goal of the initial visit is to establish a partnership between the YA and the adult provider team. Methods and expectations surrounding communication regarding urgent health questions, medication renewals, and making/canceling appointments must be discussed. Issues of privacy and consent, access and release of information, and confidentiality should also be reviewed. The YA should have the opportunity to meet with the adult team independently, without the caregiver or parent, to discuss issues openly and confidentially. In addition to the usual review of the medical summary and treatment plan, the provider should address any concerns the YA (and caregiver/support person if present) have regarding the transfer of care. Differences between pediatric and adult care should be reviewed by the adult provider.

Self-management skills should be assessed at either the initial visit or a subsequent follow-up visit so that the adult provider understands the YA’s progress in managing their health care needs. An example of this can be found on the Got Transition website (https://www.gottransition.org/6ce/?integrating-self-care-assessment) as well as in the recent position paper by NASPGHAN. ³ If a full assessment cannot be completed, consider asking the YA how important it is to manage their own health care and how confident they are in this ability. Although self-care skills assessments may not directly predict HCT success, they can be used to follow progress and tailor treatment plans to the individual for optimal outcomes.

Adult providers should be familiar with topics that may not be routinely addressed, including reproductive health (eg, contraception and avoidance of teratogenic medications), risk-taking behaviors (eg, alcohol, tobacco, drugs, and sexually transmitted infections), health insurance and anticipated changes, school and employment, support systems including coping strategies, and psychosocial health (eg, assessing for mental illness and health care–related QoL). These topics should be discussed in addition to routine health care maintenance and medical conditions associated with long-term use of immunosuppression. ³

At the end of the visit, shared care goals that reflect the partnership between the YA and adult provider should be established. The adult team should communicate with the pediatric team following the initial visit and confirm that the YA has officially transferred to adult care.

Ongoing care

Following the initial visit, a follow-up appointment should be scheduled based on medical need and the self-care skills assessment, typically no greater than 3–6 months after the initial visit. The YA should have an established primary care physician before care transfer, and the adult team will provide referrals to other adult specialists as needed. It may be helpful to establish collaborative partnerships with other specialty providers such as dermatologists, nephrologists, gynecologists, and endocrinologists interested in caring for YA patients to facilitate timely referrals. In addition to ongoing medical care and monitoring as a recipient of transplant, there should be a focus on the YA’s continuing development of self-care skills through a routine skills assessment.

Given ongoing executive functioning development, adherence to requested lab work, tests, or procedures should be monitored closely. It may be helpful to send lab reminders for at least the first year following the transfer of care. If resources permit, an adult social worker and psychologist should be included in the transition team. A study of 20 YAs (mean age 22 y) who underwent pediatric LT found that psychosocial distress was associated with nonadherence 1 year after care transfer. ³⁵ In a survey of 187 YAs (mean age 18 years), 17.7% screened positive for depression and anxiety. Fatigue, financial concerns, feeling worried, not feeling good about themselves, and sleep were the most frequently reported areas of distress. ⁸ In addition to psychology support, having YA volunteers who have been through the transition process can serve as peer support for these patients.

It is important to elicit anonymous feedback from the YA regarding the transition experience through electronic or paper surveys. In a survey assessing the adult center approach to HCT for LT, 40% of adult respondents did not routinely seek feedback from the patient or family members following the transfer of care. ²⁴ This feedback can improve the adult center’s approach to HCT.

As HCT does not stop at the time of transfer of care, the Six Core Elements of Health Care Transition can be used by adult providers as a stepwise framework to develop a systematic approach to ongoing HCT. As center resources and affiliations with pediatric providers vary, these elements should be adapted for the needs of individual centers. The core element framework will provide a pathway for collaborative engagement of both pediatric and adult providers and the YA and caregiver in the ongoing transition process.

Best practice recommendations and summary

1. Early and ongoing collaboration between pediatric and adult providers is essential during the transition process.

2. The Six Core Elements of Health Care Transition are applicable to YA pediatric recipients of LT and should be modeled to establish HCT programs in the adult transplant clinic.

3. An adaptation of the Six Core Elements pertaining to YA recipients of liver transplant is summarized in Table 1 with references to sample tools.

4. Successful HCT and integration into the adult practice is best accomplished through a multidisciplinary team approach with a focus on not only medical outcomes but psychosocial and behavioral aspects of care.

TRANSITION CLINIC IMPLEMENTATION

Several clinic models have been proposed to facilitate the transition from pediatric to adult health care. The composition of individual transition programs will depend on the availability of local personnel and resources, as well as the presence of an affiliated pediatric transplant center. In a recent study of adult LT centers, only 65% reported an affiliation with a pediatric program. ²⁴ One proposed model involves the establishment of a joint transition clinic where dedicated pediatric and adult providers work together to provide care. ³⁶ This joint clinic may be held at the adult health care center to allow the pediatric patient to become more familiar with the new setting and adult care model. These interdisciplinary clinics have been shown to increase adherence and decrease graft loss following transfer of care. ³⁷ When joint clinics are not possible, the utilization of a transition specialist or coordinator who cares for patients across both pediatric and adult health care sites may help to facilitate a smooth transition of care. ³⁸ For patients transferring to a new transplant center, communication between consulting providers is critical. In Western Australia, a clinic model was implemented that included verbal and written sign-out as well as the assignment of consultants from both pediatric and adult centers. This model allowed for overlapping care between the 2 centers during the transition period. In addition, a pediatric nurse accompanied patients to their first adult appointment. ³⁹ The underlying model is highly dependent on patient volume and availability of local resources. Consideration should also be paid to the type of health care system, which may include universal, private, or lack of health care insurance, as these may become rate-limiting factors in the organization and structure of the transition clinic.

Role of the interdisciplinary team

Successful HCT requires a structured, interdisciplinary team approach to patient care. Core team members should include hepatologists, advanced practice providers, surgeons, pharmacists, nutritionists, social workers, nurses, financial coordinators, transition navigators, psychologists, neuropsychologists, and psychiatrists when feasible.^3,34 One crucial role within this team is that of the transition navigator, which could be fulfilled by any interested team member. Having a dedicated position for this role, if resources permit, would be highly beneficial. ⁴⁰ Interdisciplinary clinics have been proven to enhance patient adherence and reduce the risk of discontinuity of care.^37,41 European and Australian centers have also reported successful outcomes and improved adherence through the implementation of multidisciplinary teams.^34,39 Such teams play a critical role in the care and transition of YAs with chronic diseases.

Role of the caretaker

The primary caretaker of the YA plays a vital role in the transfer and transition process. Typically, these caretakers have been involved in the YA’s health care since early childhood, depending on the time of onset of the liver disease or transplant. They are accustomed to assuming primary responsibility for all health care needs and decision-making, thereby making it challenging to relinquish that role. However, research by Chandra et al highlights the importance of transferring the responsibility to the YA. ³⁴ This shift is significant not only from the perspective of the primary caretaker but also from the standpoint of the pediatric medical team, who historically have tended to be overly protective of the patient. It is important to note that if caretakers pass on the responsibility to the YA too early, before they are capable of managing their own medical care, it can lead to adverse outcomes. Thus, striking a balance and managing the caretaker’s role is crucial. Education plays a vital role in empowering all stakeholders, including the patient, family, primary caretaker, and the pediatric medical team, to gradually relinquish these responsibilities and enable the YA to assume charge of their own care. The caretaker should remain involved and serve as an additional level of support when necessary. ⁴²

Best practice recommendations and summary

1. The organization and composition of individual HCT programs are center-specific and will depend on the availability of local personnel and support and the presence of an affiliated pediatric LT center.

2. HCT requires a coordinated, multidisciplinary team comprised of hepatologists, advanced practice providers, surgeons, pharmacists, nutritionists, social workers, nurses, psychologists, and psychiatrists from both the pediatric and adult teams when available.

3. A transition navigator may act as the primary facilitator in the coordination of care during the transition process.

OUTCOMES MEASURES

There are currently no standardized outcome measures for identifying successful HCT in recipients of LT beyond graft and patient survival. ³ Outcome assessments of successful HCT should include adherence measures, health care utilization/costs, and health-related quality of life (HRQoL) in addition to clinical outcomes measures as outlined in Table 2.

TABLE 2.

Suggested outcome measures of successful health care transition

Outcome	Measures
Medical outcomes
Patient survival
Allograft survival
Allograft health	Liver function tests Synthetic function Episodes of acute and chronic rejection Fibrosis stage
Long-term complications of immunosuppression	Renal insufficiency Hypertension Hyperlipidemia Diabetes Cancer Osteopenia/osteoporosis
Adherence
Medication	MLVI
Laboratory monitoring
Office visits	LTFU designation
Health care utilization
	Invasive procedures Emergency Department visits Hospitalizations Hospital length of stay Retransplantation End of life care
Health-related quality of life
	Patient satisfaction Caretaker satisfaction High school diploma or equivalent Employment Housing Financial security Anxiety/depression PTSD Substance abuse Unplanned pregnancy

Abbreviations: LTFU, lost to follow-up; MLVI, medication level variability index; PTSD, posttraumatic stress disorder.

Important primary outcome measures after transfer to the adult provider include stable graft function with good adherence and optimum HRQoL for the recipient of transplant. Secondary outcome measures include reduced morbidity associated with LT and the ability to pursue a “normal” life, including independent living, employment, and having a family. A common factor contributing to poor outcomes after transfer to the adult health care system is a lack of timely preparation and inadequate transition measures. This process requires resources, time, and commitment of all stakeholders (pediatric and adult providers, transplant recipient, and families). The cost of putting this in place is not small, but the benefits are many. In the current era, the importance of having a structured transition process to secure optimal outcomes is increasingly being recognized in centers worldwide. There are varying policies in place across transplant centers based on local resources, and hence, outcome measures tend to vary. The transition process requires adaptation to recipient factors, including those with special health care needs ⁴³ and particularly those with poor adherence. Having a transition coordinator ⁴⁴ or using a peer mentorship program ⁴⁵ may be beneficial.

Adherence

Adherence to medical recommendations is required for successful outcomes in any chronic disease, particularly in transplantation when immunosuppression, laboratory tests, and clinic visits are lifelong requirements. Subjective methods of assessing adherence are often inaccurate. Objective measures such as electronic monitoring, ⁴⁶ text messaging, ⁴⁷ and SD of immunosuppressant levels have been found to be much more reliable in determining adherence. A recent study demonstrated that the medication level variability index can be used as a tool to predict late acute rejection. Over 50% of 400 pediatric recipients of LT with a medication level variability index of >2 in a year had an episode of rejection the following year. This contrasted with only 6% of those with an index below 2. ⁴⁸

Health care utilization and costs

There is little data on health care utilization and costs following the transfer of care to an adult specialist. The majority of late graft loss is the result of acute and chronic rejection, suggesting that nonadherence may play a role. In addition, patients requiring multiple procedures, operations, and frequent readmissions during the first year after transplant have an increased incidence of late graft loss. ⁴⁹ These data support the idea that both early and late health care utilization are associated with long-term posttransplant outcomes and should be carefully monitored. Single-center data has shown a trend toward decreased adherence and increased health care utilization following transfer of care in the absence of a formal transition process. ¹

Health-related quality of life

HRQoL after transfer of care to an adult specialist is an important independent parameter to evaluate transplant outcomes. HRQoL is a multidimensional assessment of well-being, including perceived physical, mental, emotional, social, and functional status. ⁵⁰ Regular reporting of HRQoL suffers from a lack of a standardized definition due to the need for a reliable and valid instrument to translate qualitative perceptions of well-being into quantitative values for measurement and comparison that can adapt to diverse cultures and languages and be of low burden to the respondent and administrator. ⁵¹ Despite these limitations, HRQoL is of vital importance to obtain a complete picture of the outcomes after pediatric transplantation and transfer of care, particularly because of the need for long-term immunosuppression management and interaction with a new health care team at a particularly vulnerable time as a YA.

Generic tools such as the PedsQL 4.0 Generic Core Scales allow for comparisons to healthy populations, while disease-specific tools allow for evaluation of the specific issues that are affected by an illness. The disease-specific HRQoL reporting tools most relied upon include the Pediatric Quality of Life Inventory 3.0 Transplant Module (PedsQL TM) and the Pediatric Liver Transplantation Quality of Life (PeLTQL) tool. The PedsQL TM is a 46-question validated instrument encompassing 8 scales with both patient self-reporting and parent proxy-reporting on medications, transplant, pain, worry, anxiety, perception of physical appearance, and communication with health care personnel. ⁵² The PeLTQL is a 26-question validated instrument that takes 5 minutes to complete. Depression, anxiety, the liver transplant disability scale, and incidence of posttransplant lymphoproliferative disease were predictors of patient PeLTQL. ⁵³ The feasibility of integrating patient-reported outcome measures is still limited by clinical time constraints and personnel but may be aided by electronic or mobile app versions.^54,55 School performance also remains an important functional outcome reflecting independent functioning into adulthood ⁵⁶ analogous to return to employment as an adult. ⁵⁷

Despite excellent patient and graft survival, self-reported HRQoL is lower for 10-year pediatric LT survivors compared with matched healthy children. ⁵⁸ Treatment anxiety and issues around long-term medication adherence have been identified as long-term factors that may impair HRQoL. ⁵⁹ Meta-analysis has shown that HRQoL in the pediatric LT population is associated with medication adherence, sleep disturbances, and age >5 years at the time of transplantation. ⁶⁰

While the impact of transition readiness and an HCT program is not known in the pediatric LT population, transition readiness is associated with improved psychosocial QoL scores over time in patients with congenital heart disease. ⁶¹ Integrating HRQoL patient-reported outcome measures are an important indicator of LT outcomes, as well as the transition of care process.

Health care maintenance

All recipients of LT are recommended to have an annual history and physical exam, at least annual dental exams with twice yearly cleanings. ⁶² Screening for bone density loss is recommended 5 years after transplant and every 2–3 years in patients with normal bone density. Specific cancer screening is recommended by the US Preventive Services Task Force (USPSTF) guidelines, ⁶³ most notably with cervical cancer screening starting at 21 years of age. ⁶⁴ These standard recommendations are modified based on family history or individual risk, such as in patients with coexisting inflammatory bowel disease. In addition, annual skin checks are recommended due to the increased risk of skin cancer in the immunosuppressed patient. HCT takes place during adolescence and YA, a particularly crucial time to emphasize safe sex practices, inquire about alcohol and drug use, and risk-taking behaviors. As with all patients, a gender-affirming care model that is nonjudgmental and developmentally appropriate allows questions to be raised in a supportive environment. ⁶⁵ All patients are recommended to be up to date on vaccinations apart from live-attenuated vaccines. ⁶⁶

Best practice recommendations and summary

1. Outcome measures should include assessments of adherence, health care costs, and HRQoL in addition to patient and graft survival.

2. Medication level variability index can be used as a validated marker of adherence.

3. Integrating HRQoL patient-reported outcome measures an important indicator of LT outcomes and the transition of care process.

REPRODUCTIVE HEALTH

Discussions surrounding options for contraception are important following transplantation. There can be risks for both mother and child while receiving certain immunosuppressant agents (ie, mycophenolate) as well as considerations of thrombotic risks depending on the agent chosen.^67,68 Barrier methods such as condoms and diaphragm education can be provided, as they do not have any interactions with medications or thrombotic risk. However, these methods require strict compliance and may still be considered risky in the YA population due to the potential for user error.^69–71 The Centers for Disease Control’s US Medical Eligibility Criteria for Contraceptive Use (CDC USMEC) categorizes the safety of various contraceptive methods for recipients of solid organ transplant (https://www.cdc.gov/reproductivehealth/contraception/pdf/summary-chart-us-medical-eligibility-criteria_508tagged.pdf.) These recommendations are summarized in Table 3. Hormonal methods can be considered but require monitoring and overall assessment of the patient’s clinical picture to avoid thrombosis risks, particularly with estrogen-containing products.

TABLE 3.

WHO/CDC medical eligibility criteria (MEC)

Category	Description	Population
1	No restrictions on the use of the contraceptive method
2	Benefits > Risks	Uncomplicated SOT recipients
3	Risks > Benefits	Intrauterine devices (IUD) for complicated SOT
4	Unacceptable health risk if the method is used	Estrogen-containing products for complicated SOT

^aComplicated solid organ transplant (SOT) = high risk of graft failure, rejection, or presence of significant cardiac vasculopathy.

Intrauterine devices may be considered, but the risk of device-related pelvic infections should be assessed on a case-by-case basis. Intrauterine devices have been well tolerated in previous case studies. ⁶⁷ It is important to note that the CDC USMEC recommendations contrast with the recent AASLD expert guidance document, which suggests that intrauterine device use may be acceptable even in the setting of posttransplant graft failure. ⁷² Early and open conversations between patients and health care providers can facilitate the optimal choice of contraceptive method based on the patient’s preferences. If a transplant patient becomes pregnant, the team should have an immediate discussion on the medication regimen to avoid teratogenic risk and strategize monitoring for a safe pregnancy and delivery. Monitoring and prevention strategies for sexually transmitted infections should be routinely discussed with patients. Early and frequent screening in sexually active transplant patients is an important part of the transition visit and can be performed confidentially.

Best practice recommendations and summary

1. Fertility, contraception, safe-sex practices, and family planning should be routinely discussed with YA patients undergoing LT.

2. The CDC USMEC (Table 3 and 4) and AASLD provide safety recommendations and guidance for contraceptive use in recipients of transplant.

3. Early and frequent screening for sexually transmitted infections should be performed.

TABLE 4.

All contraception, ranked by MEC

Method	MEC	Advantages	Disadvantages
IUD	2/3 a	Most effective, long-acting, reversible	Heavy or irregular bleeding
Depomedroxyprogesterone acetate	2	Highly effective, decreased anemia	Decreased BMD, irregular bleeding
Progestin implant	2	Most effective, long-acting, no BMD decrease	Irregular bleeding
Combined oral contraceptives (COC)	2/4 a	Menstrual regulation, decreased anemia	Contraindicated: uncontrolled HTN, age 35 years, smokers, cardiac vasculopathy, active liver disease, personal history of MI, stroke or DVT, first-pass liver metabolism, GI disturbance may decrease absorption
Contraceptive patch	2/4 a	First-pass metabolism avoided	Contraindicated: uncontrolled HTN, age 35 years, smokers, cardiac vasculopathy, active liver disease, personal history of MI, stroke, or DVT
Vaginal ring	2/4 a	First-pass metabolism avoided, lower circulating estrogen	Contraindicated: uncontrolled HTN, active liver disease, personal history of MI, stroke, or DVT
Progestin-only pill	2	Avoid estrogen adverse effects	Less effective than COC, first-pass metabolism
Condoms	1	No drug interactions, protects from STDs	Less effective
Barrier methods	1	No drug interactions	Less effective

^aComplicated solid organ transplant SOT = high risk of graft failure, rejection, or presence of significant cardiac vasculopathy.

Abbreviations: BMD, bone mineral density; DVT, deep venous thrombosis; GI, gastrointestinal; HTN, hypertension; IUD, intrauterine device; MEC, medical eligibility criteria; MI, myocardial infarction; STI, sexually transmitted infection.

ROLE OF TECHNOLOGY IN MEDICATION ADHERENCE

Adherence to the medication regimen is a crucial component for the success of transition from the adolescent stage of care to adulthood. All members of the HCT team should assess adherence barriers and the degree of caretaker involvement with the patient’s medication regimen. The clinical pharmacist on the transition team can assist with identifying and troubleshooting barriers with adherence, cost, and timing of medications. The team can work with the patient and family to build a plan for developing independence and overcoming identified barriers. Patients in the transition window should be encouraged to take ownership of refilling medications, obtaining new medications, and addressing insurance issues with the health care team independently or with caretaker assistance.^73–75

Technology may be used as an effective strategy to improve medication adherence when accessible. Applications on smart phones and devices should be considered as a potential tool for success as these are easily accessible and can serve as a reminder for medication timing.^76–79 Mobile health applications such as Pocket PATH, Transplant Hero, Medisafe, and MyTransplant have been developed to provide medication reminders for the transplant population. Studies have demonstrated that the use of smart device applications can improve medication adherence and clinical outcomes in the transplant population. ⁷⁶ Mobile health applications will hopefully continue to be optimized to reduce medication errors, be cost-effective, and be incorporated within electronic medical records. ⁷⁷ If patients and families do not have access to smart devices, pillboxes have also been helpful in reminding patients to take medications at the correct time. The clinical pharmacist on the team should be knowledgeable of the evolving technology options while also assessing each family’s cultural and financial status to determine the most realistic strategy for medication adherence.

Best practice recommendations and summary

1. Medication adherence is a critical component of HCT and patient outcomes.

2. Technology may be used to improve medication adherence when accessible.

3. Mobile health applications and the use of pillboxes can facilitate adherence and decrease medication errors.

CONCLUSIONS

YA pediatric recipients of LT transferring from pediatric to adult health care services are highly vulnerable and subject to poor long-term outcomes. Barriers to the transition of care are multifaceted. It is important that pediatric and adult LT providers establish a partnership to optimize care for these patients. Adult providers must recognize the importance of HCT and the need to continue the transition process following the transfer of care. The overarching goal is to improve long-term outcomes for pediatric recipients of LT. To succeed in this mission, we must begin by offering consensus guidelines toward a standardized approach to transition planning. This paper outlines a framework for the implementation of a standardized, multidisciplinary approach to HCT using “The Six Core Elements of HCT.”

An obstacle to the widespread implementation of HCT programs is the current paucity of evidence linking this intervention with documented improvements in patient care. By mandating that multidisciplinary transition programs become standard practice for all LT centers, we can create the infrastructure necessary to thoroughly examine these long-term outcomes. Standardization across geographic centers will help to identify true measures of success. Successful outcomes must look beyond mere patient and graft survival and gauge important measures, such as adherence, health care costs, and HRQoL.

To implement more effective strategies and work to improve long-term outcomes for YA patients, HCT must be mandated as a routine part of posttransplant care. Increased advocacy efforts and the backing and support of governing organizations are required to help facilitate these practices.