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Abstract There is growing interest in, but limited data about, intestinal bile acid transport inhibitors as treatment for cholestatic liver disease. The current analyses combine two similar randomized placebo‐controlled trials with subsequent extension phases investigating the impact of maralixibat in children with severe cholestasis secondary to Alagille Syndrome (n = 57). The primary outcomes were measures of pruritus (ItchRO[Obs]) and clinician scratch scale (CSS), both increasing in severity from 0 to 4) and quality of life (QoL) (Parent PedsQL and Multidimensional Fatigue Scale module [MFS] scaled 0–100 with increased QoL) at week 48 of the extension phase relative to the baseline of the placebo‐controlled trials (week 13). Secondary assessments included other clinical and biochemical parameters assessed in participants at week 72 or end of treatment (after week 48). At week 48, statistically and clinically significant least square mean (95% CI) improvements in pruritus and QoL were observed (ItchRO[Obs] −1.59 [−1.81, −1.36], CSS −1.36 [−1.67, −1.05], PedsQL +10.17 [4.48, 15.86], and multidimension fatigue [MFS] +13.97 [7.85, 20.08]). At week 48, serum bile acids, platelet count, and cholesterol decreased, whereas alanine aminotransferase (ALT) increased and total bilirubin (TB) and albumin were stable. Changes were durable at week 72 and end of treatment. There were no deaths; 2 participants underwent liver transplantation. Study drug was discontinued in 9 participants after treatment‐emergent adverse events, 6 of which were events of increased ALT or TB. Conclusion: Maralixibat administration was associated with marked improvement in pruritus and QoL. Interpretation of these findings is complicated by the complex natural history of severe cholestasis in Alagille syndrome.

Elastographic measurement of liver stiffness is of growing importance in the assessment of liver disease. Pediatric experiences with this technique are primarily single center and limited in scope. The Childhood Liver Disease Research Network provided a unique opportunity to assess elastography in a well‐characterized multi‐institutional cohort. Children with biliary atresia (BA), alpha‐1 antitrypsin deficiency (A1ATD), or Alagille syndrome (ALGS) followed in a prospective longitudinal network study were eligible for enrollment in a prospective investigation of transient elastography (FibroScan). Studies were performed in participants who were nonfasted and nonsedated. Liver stiffness measurements (LSMs) were correlated with standard clinical and biochemical parameters of liver disease along with a research definition of clinically evident portal hypertension (CEPH) graded as absent, possible, or definite. Between November 2016 and August 2019, 550 participants with a mean age of 8.8 years were enrolled, 458 of whom had valid LSMs (BA, n = 254; A1ATD, n = 104; ALGS, n = 100). Invalid scans were more common in participants

Pruritus is a debilitating symptom for patients with Alagille syndrome (ALGS). In a previously reported trial of maralixibat, an investigational antipruritic agent, itching was assessed using a digital diary based on twice‐daily caregiver observation of itching severity (Itch Reported Outcome, ItchRO[Observer]). The goal of this study was to characterize pruritus in participants with ALGS at baseline in this trial, as assessed by the ItchRO instrument and the physician‐observed clinician scratch scale (CSS), relative to biomarkers putatively associated with pruritus and health‐related quality of life assessment. Thirty‐seven participants with ALGS (median age of 6 years; range 1‐17 years) were enrolled. No association was identified between CSS and ItchRO(Obs) (r = 0.22, P = 0.2). Neither CSS nor ItchRO were associated with serum bile acids (r = −0.08, P = 0.6 for both) or autotaxin (r = 0.22, P = 0.2; r = 0.28, P = 0.12). There was no significant association between Pediatric Quality of Life Inventory total parent scores and CSS or ItchRO (r = −0.23, P = 0.2; r = −0.16, P = 0.36). There was a significant association between ItchRO and Multidimensional Fatigue Scale and Family Impact Module total scores (Pearson correlation coefficient −0.575, P = 0.0005; 0.504, P = 0.002). In exploratory analysis, selected questions relating to fatigue and sleep disturbance (n = 12) from Pediatric Quality of Life Inventory, Multidimensional Fatigue Scale, and Family Impact Module were correlated with pruritus scores; positive associations were identified. Conclusion: Itching scores did not correlate with each other, nor with putative serum biomarkers of pruritus, and further, did not correlate with quality of life. Hypothesis‐generating analyses implicate sleep disturbance and fatigue as key associations with caregiver observations of itching. This is highly relevant to the selection of surrogate endpoints for clinical trials of pruritus therapies.

BackgroundAround 1800 pediatric transplantations were performed in 2021, which is approximately 5% of the annual rate of solid organ transplantations carried out in the United States. Effective family self-management in the transition from hospital to home-based recovery promotes successful outcomes of transplantation. The use of mHealth to deliver self-management interventions is a strategy that can be used to support family self-management for transplantation recipients and their families. ObjectiveThe study aims to evaluate the acceptability of an mHealth intervention (myFAMI) that combined use of a smartphone app with triggered nurse communication with family members of pediatric transplantation recipients. MethodsThis is a secondary analysis of qualitative data from family members who received the myFAMI intervention within a larger randomized controlled trial. Eligible participants used the app in the 30-day time frame after discharge and participated in a 30-day postdischarge telephone interview. Content analysis was used to generate themes. ResultsA total of 4 key themes were identified: (1) general acceptance, (2) positive interactions, (3) home management after hospital discharge, and (4) opportunities for improvement. ConclusionsAcceptability of the intervention was high. Family members rated the smartphone application as easy to use. myFAMI allowed the opportunity for families to feel connected to and engage with the medical team while in their home environment. Family members valued and appreciated ongoing support and education specifically in this first 30 days after their child’s hospital discharge and many felt it contributed positively to the management of their child’s medical needs at home. Family members provided recommendations for future refinement of the app and some suggested that a longer follow-up period would be beneficial. The development and refinement of mHealth care delivery strategies hold potential for improving outcomes for solid organ transplantation patients and their families and as a model to consider in other chronic illness populations. Trial RegistrationClinicalTrials.gov NCT03533049; https://clinicaltrials.gov/ct2/show/NCT03533049