Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The liver transplantation (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 along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 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 patient-reported experience measures spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process. 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 patient-reported experience measures, candidates of LT rated items from understanding the LT process domain as the most important. The proposed pre-LT measures provide a framework for quality improvement and care standardization among candidates of LT. 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 quality improvement initiatives to improve access and quality of care.

The impact of health literacy on adolescent and young adult pediatric liver transplant recipients.

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.

Pediatric liver transplant recipients are not just young adults: The importance of a structured health care transition program in adult transplant centers.

Health care transition (HCT) is a vulnerable period that continues into adulthood, even after the transfer of care. Given the growing population of pediatric liver transplant recipients reaching young adulthood, the need for a standardized and multidisciplinary approach to transition that spans from pediatric to adult care is becoming more imperative. In this article, we review the unique challenges and barriers to successful HCT that adolescent and young adults (AYAs) who have undergone liver transplant face, highlight the gap in transition care in the adult setting, and present the Six Core Elements of Health Care TransitionTM as a framework that can be used by adult providers to incorporate AYAs systematically and collaboratively into adult practice. Multidisciplinary HCT programs should be the standard of care for all AYAs with liver transplant, and while implementation is a necessary first step, ongoing efforts to increase awareness, funding, and research on HCTs into adulthood are needed.

Caregivers' and providers' perspectives of social and medical care after pediatric liver transplant: Results from the multicenter SOCIAL-Tx study.

Disparities exist in pediatric liver transplant (LT). We characterized barriers and facilitators to providing transplant and social care within pediatric LT clinics. This was a multicenter qualitative study. We oversampled caregivers reporting household financial strain, material economic hardship, or demonstrating poor health literacy. We also enrolled transplant team members. We conducted semistructured interviews with participants. Caregiver interviews focused on challenges addressing transplant and household needs. Transplant provider interviews focused on barriers and facilitators to providing social care within transplant teams. Interviews were recorded, transcribed, and coded according to the Capability, Opportunity, Motivation-Behavior model. We interviewed 27 caregivers and 27 transplant team members. Fifty-two percent of caregivers reported a household income <$60,000, and 62% reported financial resource strain. Caregivers reported experiencing (1) high financial burdens after LT, (2) added caregiving labor that compounds the financial burden, (3) dependency on their social network's generosity for financial and logistical support, and (4) additional support being limited to the perioperative period. Transplant providers reported (1) relying on the pretransplant psychosocial assessment for identifying social risks, (2) discomfort initiating social risk discussions in the post-transplant period, (3) reliance on social workers to address new social risks, and (4) social workers feeling overburdened by quantity and quality of the social work referrals. We identified barriers to providing effective social care in pediatric LT, primarily a lack of comfort in assessing and addressing new social risks in the post-transplant period. Addressing these barriers should enhance social care delivery and improve outcomes for these children.

The use of once-daily LCP-Tacrolimus with adolescent and young adult solid organ transplant recipients.

BACKGROUND: Adolescent and young adult (AYA) solid organ transplant (SOT) recipients experience increased rates of rejection and graft loss surrounding the time of health care transition, in part due to poor medication adherence. This study aims to examine the impact of a once-daily formulation of tacrolimus, LCP-tacrolimus (LCPT), on medication adherence for AYA SOT patients. METHODS: A retrospective descriptive analysis was performed for all patients who underwent SOT and were prescribed LCPT after the age of 12 at our single-center pediatric hospital. Medication adherence was assessed via provider documentation and the medication level variability index (MLVI). RESULTS: Twenty-nine patients were prescribed LCPT as part of their immunosuppression regimen. Twenty patients were converted to LCPT from immediate-acting (IR) tacrolimus; six patients were initiated immediately following transplant, and three patients were unable to receive LCPT due to insurance denial. There was a numeric improvement in medication adherence for converted patients when measured by provider assessment (45.0% vs. 68.4%, p = .140) and MLVI (40.0% vs. 71.4%, p = .276), though these did not reach statistical significance. There were no differences in episodes of rejection or adverse effects. LCPT prescription was not associated with decreased medication burden, and two patients transitioned back to IR tacrolimus due to increased cost. CONCLUSIONS: LCPT use did not significantly improve patient adherence; however, it resulted in numerically higher perceived and measured adherence rates. LCPT appears to be safe and effective in the management of SOT recipients; however, it may not affect pill burden and may result in a higher financial burden. Use may be considered for a select group of AYA SOT recipients.

Current approach to health care transition and integration into adult care for pediatric liver transplant recipients: A call for partnership.

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.

Health Care Transition for Adolescents and Young Adults With Pediatric-Onset Liver Disease and Transplantation: A Position Paper by the North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition.

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.

Treatment of Cholestasis in Infants and Young Children.

PURPOSE OF REVIEW: 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: 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.

Concomitant tacrolimus and ketorolac therapy in pediatric liver transplant recipients: Teaching old dogma new tricks.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ketorolac, are effective analgesic medications, but concerns for nephrotoxicity have limited their role for pain control following pediatric liver transplantation (LT). Calcineurin inhibitors (CNIs) and NSAIDs share a similar mechanism of nephrotoxicity, and concomitant administration is traditionally discouraged. A retrospective review of pediatric LT recipients was conducted between 1/1/2015 and 12/31/2019 at a single center. Patients were stratified based on receipt of ketorolac. The primary outcome was the incidence of acute kidney injury (AKI). Secondary outcomes included serum creatinine, urine output, estimated glomerular filtration rate, bleeding incidence, oral morphine milligram equivalents, and hospital length of stay (LOS). The incidence of AKI was similar between the two groups with 25.8% of patients in the ketorolac group versus 29.2% of patients in the nonketorolac group (p = .475) meeting criteria in the first 10 days post-transplant. Opioid requirements were less in the ketorolac group (p < .001), who also demonstrated shorter LOS compared with nonketorolac patients (p = .033). Concurrent CNI and ketorolac use did not result in an increased incidence of AKI in the early post-LT period and resulted in significantly lower opioid requirements along with a decreased hospital LOS.

Bone Fractures in Children With Cholestatic Liver Disease May Mimic Those Seen in Child Abuse.

ABSTRACT: Certain fractures in children are highly specific for child abuse. Metabolic bone disease frequently develops in patients with cholestatic liver disease (CLD); this can result in weakened bones and a predisposition to pathologic fractures. Fractures that occur in patients with rickets and osteopenia may mimic a bone response to inflicted injury, which in children raise the concern of child abuse. Here we report a series of 15 patients with CLD who developed pathologic fractures in the setting of metabolic bone disease. During initial evaluation, the caretakers of 5 of these 15 patients were reported to child protective services and investigated for child abuse. Pediatricians should be aware that children with CLD have an increased incidence of pathologic fractures, even after the cholestasis has resolved.

Health Care Transition: A Time of Increased Vulnerability for Pediatric Liver Transplant Recipients.

Improvements in pediatric liver transplantation (LT) have led to an increased number of patients reaching young adulthood. Young adult LT recipients transferring from pediatric to adult models of care have increased rates of rejection, graft loss, and medical complications. The goal of a health care transition program is to optimize health and assist youth in reaching their full potential. The means to achieve this goal requires an organized transition process to support youth in acquiring independent health care skills, preparing for an adult model of care, and transferring to new providers without disruption in treatment. This can only be achieved through a multidisciplinary approach to transition planning. This is often a labor and resource-intensive undertaking, which may not receive the necessary support from local institutions. Widespread implementation requires the assistance and endorsement from governing organizations at the national and international level.

Role of Budesonide for the Treatment of Rejection in Pediatric Liver Transplantation.

INTRODUCTION: Corticosteroids are an integral part of liver transplant (LT) immunosuppression regimens but are often accompanied by many adverse effects. Budesonide is an oral corticosteroid with extensive (80%-90%) hepatic first-pass metabolism and minimal systemic absorption. The aim of this study was to examine the safety and efficacy of budesonide for management of acute cellular rejection (ACR) in pediatric LT recipients. METHODS: A retrospective descriptive analysis was performed for all pediatric patients who underwent LT at our center and were prescribed oral budesonide for the treatment of ACR. Alanine aminotransferase (ALT) values and documented adverse effects were reviewed. RESULTS: Twenty-nine patients were prescribed budesonide for the treatment of ACR; 65.5% with biopsy-proven acute rejection and 34.5% with presumed ACR. There was a significant decrease in ALT noted from the time of rejection when compared to values 1 month (P = 0.0011), 3 months (P = 0.0003), and 6 months (P = 0.0001) after treatment with budesonide. There was no difference noted between patient baseline ALT levels before rejection when compared to 1, 3, and 6 months posttreatment values suggesting resolution of rejection. Three patients required conversion from budesonide to systemic steroids. There were no discontinuations of budesonide secondary to adverse effects. CONCLUSION: Oral budesonide may be a promising alternative to systemic corticosteroids for the management of mild/moderate ACR and for empiric treatment of ACR in select pediatric LT recipients. Data from this study may provide the foundation for larger, prospective, multicenter trials to assess the effectiveness of budesonide in the treatment of ACR.

Adherence, Medical Outcomes, and Health Care Costs in Adolescents/Young Adults Following Pediatric Liver Transplantation.

OBJECTIVE: Improved outcomes after pediatric liver transplantation (LT) have led to increasing numbers of adolescent and young adult recipients entering into adult health care systems. The aim of this study was to evaluate the impact of transition from pediatric to adult health care models on medical outcomes, measures of adherence, and health care utilization for pediatric LT recipients. METHODS: We evaluated the course of patients who received an LT while followed in pediatrics and transferred to an adult care provider within our institution. Data were collected from 2 years preceding and 2 years following transfer of care. RESULTS: A total of 32 patients were eligible for analysis. Median age at time of transfer was 22.9 years (interquartile range 21.7-23.6). Nine patients (28%) died following transfer of care. There was a significant decrease in office visit adherence following transfer of care (P = 0.02). Although not achieving significance, an increase in alanine aminotransferase values, episodes of acute cellular rejection, progression to cirrhosis, evolution to chronic rejection, and hospital admission rates post transfer were found. These findings were associated with an increase in health care costs related to required interventions. CONCLUSIONS: Our study demonstrates trends toward worse health outcomes, decreased adherence, and increased health care utilization following transfer of care. These findings and poor patient survival suggest that the time around transition from pediatric to adult health care models represents a period of increased vulnerability for pediatric LT recipients. Larger, multicenter, prospective studies are needed to identify factors and interventions that affect adolescent and young adult to improve the transition process.

A case of an Infant with SARS-CoV-2 hepatitis early after liver transplantation.

We present a case of a pediatric liver transplant recipient diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection four days after receiving a living donor liver allograft from her mother. The recipient was a 6-month-old with end-stage liver disease due to biliary atresia and failed Kasai. The infant had an uncomplicated implantation, excellent graft function and down-trending liver enzymes until developing fevers, diarrhea, and moderate respiratory distress requiring non-invasive respiratory support. SARS-CoV-2 testing (nasal swab Polymerase Chain Reaction) was positive on post-operative day (POD) 4. Liver enzymes peaked ~1000 U/L (5-fold higher than the previous day) on POD 6. Histology demonstrated a mixed picture of moderate acute hepatitis and classical elements of mild to moderate acute cellular rejection. Her hepatitis and respiratory symptoms improved coincident with completing treatment with hydroxychloroquine, reduced immunosuppression, and intravenous gamma globulin (IVIG).

Management of Wilson Disease Diagnosed in Infancy: An Appraisal of Available Experience to Generate Discussion.

Increased access to molecular genetic testing is changing the demographics for diagnosing inherited disorders and imposing new challenges for medical management. Wilson disease (WD), typically diagnosed in older children and adults, can now be detected in utero and in infants (children younger than 24 months, including neonates) via genetic testing. An evidence-based approach to management of these neonates and extremely young children, who are typically asymptomatic, has been hampered by lack of clinical experience. We present a case of an infantile diagnosis of WD, review available experience, and discuss current trends in antenatal genetic testing of parents and fetus that may lead to a very early diagnosis of WD. Based on physiological and nutritional considerations, we propose an algorithmic approach to management of infantile WD as a starting point for further discussion. Future collaboration amongst specialists is essential to identify evidence-based approaches and best practice for managing treatment of infants with genetically diagnosed WD.

Partial Splenic Embolization Is a Safe and Effective Alternative in the Management of Portal Hypertension in Children.

OBJECTIVE: There are multiple approaches to manage the clinical complications of portal hypertension (PHTN) to treat/prevent spontaneous hemorrhage by mitigating thrombocytopenia. No single approach is ideal for all patients given the heterogeneity of this population. Our goal was to determine whether partial splenic embolization (PSE) was safe and effective in the pediatric population. METHODS: This is a retrospective review of our single-center experience for all patients ages 0 to 21 who underwent PSE between January 2010 and August 2017. The embolized splenic volume targeted was 60% to 70%. RESULTS: Twenty-six patients underwent PSE due to thrombocytopenia and/or recurrent variceal bleeding. Patients ranged in age from 18 months to 20 years (mean 13.1 years). The median platelet count before PSE was 53.0 (×10/L). The platelet count improved after PSE with values >100,000 in 21 patients (80.8%). Children with prior esophageal varices showed improvement after PSE with only 9 (34.6%) requiring further endoscopic therapy. After PSE, patients developed transient abdominal pain, distention, fever, and perisplenic fluid collections. Serious complications such as splenic abscess, splenic rupture, bleeding, pancreatic infarction, opportunistic infection, or death were not observed. One patient experienced thrombotic complications after PSE and was later diagnosed with myelodysplastic syndrome. CONCLUSIONS: PSE is a safe and effective alternative in the management of pediatric PHTN in select populations. PSE may be a favorable alternative to splenectomy and portal systemic shunting because it preserves functional spleen mass and avoids postprocedure accelerated liver disease or encephalopathy.

Roux-en-Y enterolith leading to obstruction and ischemic necrosis after pediatric orthotopic liver transplantation.

Biliary complications are a common cause of morbidity after liver transplantation, with biliary stone formation being a known occurrence generally upstream of a stricture. A 12-year-old boy, who underwent an orthotopic liver transplantation at 11 months of age for biliary atresia, presented acutely with fever and abdominal pain. Cross-sectional imaging revealed Roux-en-Y limb dilatation and thickening. He was explored and was found to have an ischemic Roux limb secondary to an obstructing enterolith. A segmental bowel resection and revision of his hepaticojejunostomy was performed. While rare, biliary enteroliths may present as either a bowel obstruction or cholangitis and should be considered in the differential diagnosis of a patient following biliary reconstruction. Additionally, anatomic etiologies should be considered and potentially surgically corrected.

Enteric serotonin and oxytocin: endogenous regulation of severity in a murine model of necrotizing enterocolitis.

Necrotizing enterocolitis (NEC), a gastrointestinal inflammatory disease of unknown etiology that may also affect the liver, causes a great deal of morbidity and mortality in premature infants. We tested the hypothesis that signaling molecules, which are endogenous to the bowel, regulate the severity of intestinal and hepatic damage in an established murine NEC model. Specifically, we postulated that mucosal serotonin (5-HT), which is proinflammatory, would exacerbate experimental NEC and that oxytocin (OT), which is present in enteric neurons and is anti-inflammatory, would oppose it. Genetic deletion of the 5-HT transporter (SERT), which increases and prolongs effects of 5-HT, was found to increase the severity of systemic manifestations, intestinal inflammation, and associated hepatotoxicity of experimental NEC. In contrast, genetic deletion of tryptophan hydroxylase 1 (TPH1), which is responsible for 5-HT biosynthesis in enterochromaffin (EC) cells of the intestinal mucosa, and TPH inhibition with LP-920540 both decrease the severity of experimental NEC in the small intestine and liver. These observations suggest that 5-HT from EC cells helps to drive the inflammatory damage to the gut and liver that occurs in the murine NEC model. Administration of OT decreased, while the OT receptor antagonist atosiban exacerbated, the intestinal inflammation of experimental NEC. Data from the current investigation are consistent with the tested hypotheses-that the enteric signaling molecules, 5-HT (positively) and OT (negatively) regulate severity of inflammation in a mouse model of NEC. Moreover, we suggest that mucosally restricted inhibition of 5-HT biosynthesis and/or administration of OT may be useful in the treatment of NEC.NEW & NOTEWORTHY Serotonin (5-HT) and oxytocin reciprocally regulate the severity of intestinal inflammation and hepatotoxicity in a murine model of necrotizing enterocolitis (NEC). Selective depletion of mucosal 5-HT through genetic deletion or inhibition of tryptophan hydroxylase-1 ameliorates, while deletion of the 5-HT uptake transporter, which increases 5-HT availability, exacerbates the severity of NEC. In contrast, oxytocin reduces, while the oxytocin receptor antagonist atosiban enhances, NEC severity. Peripheral tryptophan hydroxylase inhibition may be useful in treatment of NEC.

Caregiver Perceptions of Social Risk Screening in Pediatric Liver Transplantation: From the Multicenter SOCIAL-Tx Study.

BACKGROUND: The social determinants of health contribute to adverse post-liver transplant outcomes. Identifying unmet social risks may enable transplant teams to improve long-term outcomes for at-risk children. However, providers may feel uncomfortable asking about household-level social risks in the posttransplant period because they might make their patients/families uncomfortable. METHODS: We conducted a mixed-methods analysis of caregiver participants (ie, parents/guardians of pediatric liver transplant recipients) in the Social and Contextual Impact on Children Undergoing Liver Transplantation study to assess their perceptions of provider-based social risk screening. Participants (N = 109) completed a 20-min social determinants of health questionnaire that included questions on the acceptability of being asked intimate social risk questions. A subset of participants (N = 37) engaged in an in-depth qualitative interview to share their perceptions of social risk screening. RESULTS: Of 109 participants across 9 US transplant centers, 60% reported financial strain and 30% reported at least 1 material economic hardship (eg, food insecurity, housing instability). Overall, 65% of respondents reported it very or somewhat appropriate and 25% reported being neutral to being screened for social risks in a liver transplant setting. In qualitative analyses, participants reported trust in the providers and a clear understanding of the intention of the screening as prerequisites for liver transplant teams to perform social risk screening. CONCLUSIONS: Only a small minority of caregivers found social risk screening unacceptable. Pediatric liver transplant programs should implement routine social risk screening and prioritize the patient and family voices when establishing a screening program to ensure successful implementation.