Faculty Bibliography

Pediatric liver transplant recipients have increased rates of morbidity and mortality following transfer to adult health care providers. The role of health literacy (HL) has not been adequately assessed in this population and may be an unrecognized barrier to successful health care transition. We sought to determine the impact of HL for patients and their caregivers on measures of transition readiness (TR), adherence, health-related quality of life, and medical outcomes following pediatric liver transplant. This is a single-center study of pediatric liver transplant recipients transplanted between the ages of 12 and 26 from October 2016 through August 2020. Patients and caregivers completed 4 surveys to evaluate TR, health-related quality of life, and HL. Clinical outcomes were stratified based on the presence or absence of adequate HL. Limited HL was identified in 57.0% of recipients and 47.4% of caregivers. Patients with limited HL were more likely to be younger in age ( p = 0.004), Hispanic ( p = 0.003), and less likely to have obtained a high school diploma or equivalent ( p < 0.001). Patients with adequate HL demonstrated significantly higher levels of TR ( p < 0.001). Patient HL did not impact health-related quality of life, adherence, or medical outcomes. Caregiver HL did not impact patient outcomes or adherence, though higher levels of caregiver education were associated with adequate patient HL ( p = 0.049). This study demonstrates that limited HL is associated with decreased measures of TR. Inadequate HL may be an unrecognized barrier to a successful health care transition. Regular assessment of HL may provide an opportunity for intervention prior to transfer of care. Future studies should investigate the impact of these interventions on long-term medical outcomes.

INTRODUCTION/BACKGROUND:The LT evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures (PREMs) along the continuum of pre-LT care to reduce care variation and guide patient-centered care. METHODS:Following a systematic literature review, candidate pre-LT measures were grouped into four phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care and social work selected the final set. Candidate PREMs spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. RESULTS:Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures and 10 were outcome measures that focused on elements not typically measured in routine care. Among the PREMs, LT candidates rated items from understanding the LT process domain as the most important. CONCLUSION/CONCLUSIONS:The proposed pre-LT measures provide a framework for quality improvement and care standardization among LT candidates. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local QI initiatives to improve access and quality of care.

Exome sequencing (ES) has been used in a variety of clinical settings but there are limited data on its utility for diagnosis and/or prediction of monogenic liver diseases. We developed a curated list of 502 genes for monogenic disorders associated with liver phenotypes and analyzed ES data for these genes in 758 patients with chronic liver diseases (CLD). For comparison, we examined ES data in 7856 self-declared healthy controls (HC), and 2187 patients with chronic kidney disease (CKD). Candidate pathogenic (P) or likely pathogenic (LP) variants were initially identified in 19.9% of participants, most of which were attributable to previously reported pathogenic variants with implausibly high allele frequencies. After variant annotation and filtering based on population minor allele frequency (MAF ≤ 10^-4 for dominant disorders and MAF ≤ 10^-3 for recessive disorders), we detected a significant enrichment of P/LP variants in the CLD cohort compared to the HC cohort (X² test OR 5.00, 95% CI 3.06-8.18, p value = 4.5e-12). A second-level manual annotation was necessary to capture true pathogenic variants that were removed by stringent allele frequency and quality filters. After these sequential steps, the diagnostic rate of monogenic disorders was 5.7% in the CLD cohort, attributable to P/LP variants in 25 genes. We also identified concordant liver disease phenotypes for 15/22 kidney disease patients with P/LP variants in liver genes, mostly associated with cystic liver disease phenotypes. Sequencing results had many implications for clinical management, including familial testing for early diagnosis and management, preventative screening for associated comorbidities, and in some cases for therapy. Exome sequencing provided a 5.7% diagnostic rate in CLD patients and required multiple rounds of review to reduce both false positive and false negative findings. The identification of concordant phenotypes in many patients with P/LP variants and no known liver disease also indicates a potential for predictive testing for selected monogenic liver disorders.

PURPOSE OF REVIEW/OBJECTIVE:Cholestasis is characterized by a conjugated hyperbilirubinemia secondary to impaired bile synthesis, transport, or excretion from the liver. It is always pathologic and can be indicative of an underlying hepatobiliary, genetic, or metabolic disorder, several of which require timely diagnosis to ensure proper management and optimal outcomes. This review provides an overview of the evaluation of cholestasis with a focus on current and emerging treatment strategies. RECENT FINDINGS/RESULTS:Increased accessibility of next generation sequencing (NGS) allows for utilization of genetic testing early in the diagnostic process. This may alter the clinical algorithm for diagnosis of cholestatic disorders. An enhanced understanding of the underlying pathophysiology may help guide future development of targeted therapies, such as ileal bile acid transporter (IBAT) inhibitors. These were recently approved for treatment of cholestatic pruritus in patients with Alagille syndrome and Progressive Familial Intrahepatic Cholestasis. Current management of cholestasis is aimed at the biochemical consequences of impaired bile flow, including malnutrition, pruritus, and progressive fibrosis. NGS has led to an enhanced understanding of biliary pathology and may guide development of future treatment modalities based on specific gene mutations. Rapid discernment of the underlying etiology is essential as new treatment modalities emerge.

Despite the increased risk of non-adherence, allograft rejection, and mortality following transfer from pediatric to adult care in liver transplantation (LT), there is no standardized approach to health care transition (HCT). Two electronic national surveys were developed and distributed to members of the Society for Pediatric Liver Transplantation and all adult LT programs in the United States to examine current HCT practices. Responses were received from 40 pediatric and 79 adult centers. Pediatric centers were more likely to focus on HCT noting the presence of a transition/transfer policy (60.2% vs. 39.2%), transition clinic (51.6% vs. 16.5%), and the routine use of transition readiness assessment tools (54.8% vs. 10.2%). Perceived barriers to HCT were similar among pediatric and adult respondents and included patient willingness to transfer and participate in care, failure to show for appointments, and lack of sufficient time and staffing. These results highlight the need for an increased awareness of HCT at both pediatric and adult LT centers. The path to improvement requires a partnership between pediatric and adult providers. Recognizing the importance of a comprehensive HCT program initiated in pediatrics and continued throughout young adulthood with ongoing support by the adult team is essential.

Advances in medical therapies and liver transplantation have resulted in a greater number of pediatric patients reaching young adulthood. However, there is an increased risk for medical complications and morbidity surrounding transfer from pediatric to adult hepatology and transplant services. Health care transition (HCT) is the process of moving from a child/family-centered model of care to an adult or patient-centered model of health care. Successful HCT requires a partnership between pediatric and adult providers across all disciplines resulting in a transition process that does not end at the time of transfer but continues throughout early adulthood. Joint consensus guidelines in collaboration with the American Society of Transplantation are presented to facilitate the adoption of a structured, multidisciplinary approach to transition planning utilizing The Six Core Elements of Health Care Transition TM for use by both pediatric and adult specialists. This paper provides guidance and seeks support for the implementation of an HCT program which spans across both pediatric and adult hepatology and transplant centers.