Barriers to access in pediatric living‐donor liver transplantation

Children receiving a LDLT have superior post‐transplant outcomes, but this procedure is only used for 10% of transplant recipients. Better understanding about barriers toward LDLT and the sociodemographic characteristics that influence these underlying mechanisms would help to inform strategies to increase its use. We conducted an online, anonymous survey of parents/caregivers for children awaiting, or have received, a liver transplant regarding their knowledge and attitudes about LDLT. The survey was completed by 217 respondents. While 97% of respondents understood an individual could donate a portion of their liver, only 72% knew the steps in evaluation, and 69% understood the donor surgery was covered by the recipient's insurance. Individuals with public insurance were less likely than those with private insurance to know the steps for LDLT evaluation (44% vs 82%; P < 0.001). Respondents with public insurance were less likely to know someone that had been a living donor (44% vs 56%; P = 0.005) as were individuals without a college degree (64% vs 85%; P = 0.007). Nearly all respondents generally trusted their healthcare team. Among respondents, 82% believed they were well‐informed about LDLT but individuals with public insurance were significantly less likely to feel well‐informed (67% vs 87%; P = 0.03) and to understand how donor surgery might impact donor work/time off (44% vs 81%; P = 0.001). Substantial gaps exist in parental understanding about LDLT, including its evaluation, potential benefits, and complications. Greater emphasis on addressing these barriers, especially to individuals with fewer resources, will be helpful to expand the use of LDLT

Durability of Response in Children Treated with Pegylated Interferon alfa-2a +/- Ribavirin for Chronic Hepatitis C

Objectives: No long-term data have been published on the durability of response following pegylated interferon (PegIFN) treatment in children with chronic hepatitis C. This prospective, multicenter, long-term follow-up (LTFU) study aimed to assess long-term durability of sustained virological response (SVR), long-term safety and tolerability, and the association between IL28B genotype and treatment response, in children previously treated with PegIFN alfa-2a ± ribavirin (RBV) in the PEDS-C trial. Methods: A total of 93 patients were assessed for enrollment, and 38 enrolled in the study. Patients attended 2 study visits: 5 (mean 5.6, range 4.1–6.6) and 6 (6.6, 5.1–7.7) years after treatment cessation. Standardized medical history, physical examination, and laboratory testing were performed at these visits. Reminder telephone calls were conducted at 4 and 8 months after the initial visit. Results: The LTFU cohort was the representative of the original PEDS-C cohort because both baseline and treatment characteristics were comparable. Of the 38 participants, 21 achieved SVR (responders) during the PEDS-C trial and 17 had not (nonresponders). All 21 responders maintained undetectable hepatitis C virus RNA during the LTFU (4.4–7.0 years after achieving SVR) in contrast to the nonresponders who demonstrated persistent viremia. IL28B CC genotype was associated with SVR (67% vs 30% in non-CC, P = 0.028). Conclusion: Long-term durability of SVR is excellent following PegIFN alfa-2a treatment in children with chronic hepatitis C; SVR is higher in those with IL28B CC versus non-CC

Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children : An International Observational Study

Background and Aims Recurrent primary sclerosing cholangitis (rPSC) following liver transplant (LT) has a negative impact on graft and patient survival; little is known about risk factors for rPSC or disease course in children. Approach and Results We retrospectively evaluated risk factors for rPSC in 140 children from the Pediatric PSC Consortium, a multicenter international registry. Recipients underwent LT for PSC and had >90 days of follow-up. The primary outcome, rPSC, was defined using Graziadei criteria. Median follow-up after LT was 3 years (interquartile range 1.1-6.1). rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively. Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01). Inflammatory bowel disease was more prevalent in the rPSC group (86% vs. 66%; P = 0.025). After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04). In those with rPSC, 43% developed complications of portal hypertension, were relisted for LT, or died within 2 years of the diagnosis. Mortality was higher in the rPSC group (11.1% vs. 2.9%; P = 0.05). Conclusions The incidence of rPSC in this cohort was higher than previously reported, and was associated with increased morbidity and mortality. Patients with rPSC appeared to have a more aggressive, immune-reactive phenotype. These findings underscore the need to understand the immune mechanisms of rPSC, to lay the foundation for developing new therapies and improve outcomes in this challenging population.Peer reviewe

Predictors of 6-year event-free survival in Alagille syndrome patients treated with maralixibat, an ileal bile acid transporter inhibitor

Background and Aims: Refractory pruritus and other complications of cholestasis are indications for liver transplantation (LT) in patients with Alagille syndrome (ALGS). We evaluated predictors of event-free survival and transplant-free survival in patients with ALGS treated with maralixibat (MRX), an ileal bile acid transporter inhibitor. Approach and Results: We assessed patients with ALGS from 3 clinical trials of MRX with up to 6 years of follow-up. Event-free survival was defined as the absence of LT, surgical biliary diversion, hepatic decompensation, or death; transplant-free survival was the absence of LT or death. Forty-three potential predictors were evaluated, including age, pruritus (ItchRO[Obs] 0–4 scale), biochemistries, platelets, and serum bile acids. Harrell’s concordance statistic assessed goodness-of-fit, and then, Cox proportional hazard models confirmed the statistical significance of the predictors identified. A further analysis was performed to identify cutoffs using a grid search. Seventy-six individuals met the criteria of receiving MRX for ≥ 48 weeks with laboratory values available at week 48 (W48). The median duration of MRX was 4.7 years (IQR: 1.6–5.8); 16 had events (10 LT, 3 decompensation, 2 death, and 1 surgical biliary diversion). The 6-year event-free survival improved with a clinically meaningful &gt; 1-point ItchRO(Obs) reduction from baseline to W48 (88% vs. 57%; p = 0.005), W48 bilirubin &lt; 6.5 mg/dL (90% vs. 43%; p &lt; 0.0001), and W48 serum bile acid &lt; 200 µmol/L (85% vs. 49%; p = 0.001). These parameters were also predictive of 6-year transplant-free survival. Conclusions: Improvement in pruritus by 48 weeks, and lower W48 bilirubin and serum bile acid levels were associated with fewer events. These data may help identify potential markers of disease progression for ALGS patients treated with MRX.</p

Role for Social Media in Pediatric Liver Disease: Caregiver and Provider Perspectives

To better understand the benefits and harms of engagement with online pediatric liver disease communities within social media. We conducted a survey of caregivers of children with liver disease participating in online pediatric liver disease communities within social media, as well as a survey of healthcare providers (e.g., physicians, surgeons, nurse coordinators) from this field to better understand the perceived benefits and harms of participation. Among 138 caregivers of children with liver disease that completed the survey, 97.8% agreed social media was a good place to learn about patient experiences and 88% agreed it was a good source of general information. Among caregivers, 84.8% agreed social media helps them to better advocate for their child. While 18% agreed that the information over social media was equal to the information from their healthcare team and 19% neither agreed/disagreed, only 3% indicated they would use this information to change care without telling their provider; in contrast, among 217 healthcare providers, 55% believed social media may lead caregivers to change management without telling their team. Engagement with online disease-specific communities in social media yields several benefits for caregivers and, in contrast to healthcare providers' concerns, participation is unlikely to lead to problems including caregivers changing the treatment plan without first discussing these plans with their team. Openness between caregivers and medical teams about the role for social media can help to improve trust and maximize the potential benefits of engagement with these groups

The Impact of Increased Allocation Priority for Children Awaiting Liver Transplant: A Liver Simulated Allocation Model (LSAM) Analysis

Objective: The aim of the study was to investigate the impact of prioritizing infants, children, adolescents, and the sickest adults (Status 1) for deceased donor livers. We compared outcomes under two "SharePeds" allocation schema, which prioritize children and Status 1 adults for national sharing and enhanced access to pediatric donors or all donors younger than 35 years, to outcomes under the allocation plan approved by the Organ Procurement and Transplant Network in December 2017 (Organ Procurement and Transplantation Network [OPTN] 12-2017). Methods: The 2017 Liver Simulated Allocation Model and Scientific Registry of Transplant Recipients data on all US liver transplant candidates and liver offers 7/2013 to 6/2016 were used to predict waitlist deaths, transplants, and post-transplant deaths under the OPTN 12-2017 and SharePeds schema. Results: Prioritizing national sharing of pediatric donor livers with children (SharePeds 1) would decrease waitlist deaths for infants (< 2 years, P = 0.0003) and children (2-11 years, P = 0.001), with no significant change for adults (P = 0.13). Prioritizing national sharing of all younger than 35-year-old deceased donor livers with children and Status 1A adults (SharePeds 2) would decrease waitlist deaths for infants, children, and all Status 1A/B patients (P < 0.0001 for each). SharePeds 1 and 2 would increase the number of liver transplants done in infants, children, and adolescents compared to the OPTN-2017 schema (P < 0.00005 for all age groups). Both SharePeds schema would increase the percentage of pediatric livers transplanted into pediatric recipients. Conclusions: Waitlist deaths could be significantly decreased, and liver transplants increased, for children and the sickest adults, by prioritizing children for pediatric livers and with broader national sharing of deceased donor livers

PoopMD, a Mobile Health Application, Accurately Identifies Infant Acholic Stools

<div><p>Biliary atresia (BA) is the leading cause of pediatric end-stage liver disease in the United States. Education of parents in the perinatal period with stool cards depicting acholic and normal stools has been associated with improved time-to-diagnosis and survival in BA. PoopMD is a mobile application that utilizes a smartphone’s camera and color recognition software to analyze an infant’s stool and determine if additional follow-up is indicated. PoopMD was developed using custom HTML5/CSS3 and wrapped to work on iOS and Android platforms. In order to define the gold standard regarding stool color, seven pediatricians were asked to review 45 photographs of infant stool and rate them as acholic, normal, or indeterminate. Samples for which 6+ pediatricians demonstrated agreement defined the gold standard, and only these samples were included in the analysis. Accuracy of PoopMD was assessed using an iPhone 5s with incandescent lighting. Variability in analysis of stool photographs as acholic versus normal with intermediate rating weighted as 50% agreement (kappa) was compared between three laypeople and one expert user. Variability in output was also assessed between an iPhone 5s and a Samsung Galaxy S4, as well as between incandescent lighting and compact fluorescent lighting. Six-plus pediatricians agreed on 27 normal and 7 acholic photographs; no photographs were defined as indeterminate. The sensitivity was 7/7 (100%). The specificity was 24/27 (89%) with 3/27 labeled as indeterminate; no photos of normal stool were labeled as acholic. The Laplace-smoothed positive likelihood ratio was 6.44 (95% CI 2.52 to 16.48) and the negative likelihood ratio was 0.13 (95% CI 0.02 to 0.83). kappa_user was 0.68, kappa_phone was 0.88, and kappa_light was 0.81. Therefore, in this pilot study, PoopMD accurately differentiates acholic from normal color with substantial agreement across users, and almost perfect agreement across two popular smartphones and ambient light settings. PoopMD may be a valuable tool to help parents identify acholic stools in the perinatal period, and provide guidance as to whether additional evaluation with their pediatrician is indicated. PoopMD may improve outcomes for children with BA.</p></div

Example of stool photographs presented to panel of pediatricians for development of gold standard.

<p>Example of stool photographs presented to panel of pediatricians for development of gold standard.</p

RGB hexcodes denoting the spectrum of abnormal and normal stool colors.

<p>RGB hexcodes denoting the spectrum of abnormal and normal stool colors.</p