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Chronic hepatitis C viral infection represents a worldwide viral epidemic. The natural course of hepatitis C virus is less understood in the pediatric population, although fewer children progress to cirrhosis and end-stage liver disease than adults infected. In the last five years, epidemiological and clinical research involving hepatitis C virus-infected children has raised interesting observations regarding the differences in transmission, natural history, and response to treatment in this population. [ABSTRACT FROM AUTHOR]

Objective: To assess frailty, a measure of physiologic declines in multiple organ systems, in children with chronic liver disease using a novel pediatric frailty tool.Study Design: We performed a prospective cross-sectional multicenter study at 17 liver transplantation (LT) centers. 71 children (5-17 years of age), 36 with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) and listed for LT, were assessed for frailty using validated pediatric tools to assess the 5 classic Fried Frailty Criteria-slowness, weakness, exhaustion, diminished physical activity, and shrinkage. Test scores were translated to age- and sex-dependent z scores, generating a maximum frailty score of 10.Results: The median frailty score of the cohort was 4 (IQR 3, 5). Subjects with ESLD had significantly higher frailty scores (median 5; IQR 4, 7) than subjects with CCLD (median 3; IQR 2, 4); (P <  .0001). Area under the curve receiver operating characteristic for frailty scores to discriminate between ESLD and CCLD was 0.83 (95% CI 0.73, 0.93). Forty-six percent of children with ESLD were frail and there was no correlation between pediatric frailty scores and physician's global assessments (r = -0.24, 95% CI -0.53, 0.10).Conclusions: A novel frailty tool assessed additional dimensions of health, not captured by standard laboratory measures and identified the sickest individuals among a cohort of children with chronic liver disease. This tool may have applicability to other children with chronic disease. [ABSTRACT FROM AUTHOR]

Background: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID‐19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long‐term antibody durability beyond this timeframe following three doses of the SARS‐CoV‐2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs. Methods: Participants in a multi‐center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS‐CoV‐2 spike protein receptor‐binding domain (Roche Elecsys anti‐SARS‐CoV‐2‐S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1‐, 3‐, and 6‐months post‐D3. Participants were surveyed at each timepoint and at 12‐months post‐D3. Results: All 34 participants had positive anti‐RBD antibody titers 6 months post‐D3. Variations in titers occurred between 3 and 6 months post‐D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3‐month post‐D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6–12 months following the third dose of the SARS‐CoV‐2 mRNA vaccine. Conclusions: The results suggest that antibody durability persists up to 6 months following three doses of the SARS‐CoV‐2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune‐evasive nature of novel variants such as Omicron. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection during the Omicron period was frequent amongst a cohort of vaccinated pediatric solid organ transplant recipients (pSOTRs) despite robust anti-receptor-binding domain (anti-RBD) antibody response, suggesting poor neutralizing capacity against Omicron subvariants. Breakthrough infections among pSOTRs were overall limited in severity. [ABSTRACT FROM AUTHOR]

Background: There has not been a comprehensive global survey of pediatric‐deceased donor allocation practices across all organs since the advent of deceased donor transplantation at the end of the 20th century. As an international community that is responsible for transplanting children, we set out to survey the existing landscape of allocation. We aimed to summarize current practices and provide a snapshot overview of deceased donor allocation practices to children across the world. Methods: The International Registry in Organ Donation and Transplantation (IRODAT, www.irodat.org) was utilized to generate a list of all countries in the world, divided by continent, that performed transplantation. We reviewed the published literature, published allocation policy, individual website references and associated links to publicly available listed allocation policies. Following this, we utilized tools of communication, relationships, and international fellowship to confirm deceased donation pediatric centers and survey pediatric allocation practices for liver, kidney, heart, and lung across the world. We summarize pediatric allocation practices by organ when available using source documents, and personal communication when no source documents were available. Results: The majority of countries had either formal or informal policies directed toward minimizing organ distribution disparity among pediatric patients. Conclusion: Children have long‐term life to gain from organ donation yet continue to die while awaiting transplantation. We summarize global strategies that have been employed to provide meaningful and sustained benefit to children on the waitlist. [ABSTRACT FROM AUTHOR]

Background: Patient‐reported outcome measures (PROMs) are not routinely used in clinical care by pediatric liver transplant (LT) teams. The Starzl Network for Excellence in Pediatric Transplantation (SNEPT) assessed feasibility of using a disease‐specific Quality of Life (QoL) questionnaire in the ambulatory setting at 10 SNEPT sites. Methods: A mixed methods feasibility project assessing administration processes, barriers, and user experiences with the Pediatric Liver Transplant Quality of Life (PeLTQL) tool. Iterative processes sought stakeholder feedback across four phases (Pilot, Extended Pilot, Development of a Mobile App PeLTQL version, and Pilot App use). Results: A total of 149 patient–parent dyads completed the PeLTQL during LT clinic follow‐up. Clinicians, parents, and patients evaluated and reported on feasibility of operationalization. Only two of 10 SNEPT sites continued PeLTQL administration after the initial two pilot phases. Reasons include limited clinical time and available personnel aggravated by the COVID‐19 pandemic. In response, a mobile application version of the PeLTQL was initiated. Providing PeLTQL responses electronically was "very easy" or "easy" as reported by 96% (22/23) parents. Conclusions: Administration of a PROM into post‐pediatric LT clinical care was feasible, but ongoing utilization stalled. Use of a mobile app towards facilitating completion of the PeLTQL outside of clinic hours may address the time and work‐flow barriers identified. [ABSTRACT FROM AUTHOR]

Background: Retrospective studies have demonstrated the efficacy and safety of pediatric and adolescent transjugular intrahepatic portosystemic shunt (TIPS), but long-term outcomes warrant further investigation. Objective: To report on the development of hyperplastic hepatic nodular lesion development in children and young adults (<21 years) with TIPS patency >3 years. Materials and methods: Eighteen children and young adults, including 10 (55.6%) females and 8 (44.4%) males, underwent TIPS creation with >3 years' patency and follow-up evaluation at a tertiary children's hospital. The mean age at the time of TIPS creation was 12.5±5.1 years (range: 1.5–20.0 years). The mean model for end-stage liver disease (MELD) at the time of TIPS creation was 8.1±1.6 (range: 6–11). Indications for TIPS creation included acute variceal bleeding (8/18, 44.4%), primary (1/18, 5.6%) or secondary (7/18, 38.9%) prevention of varices, portal vein thrombosis (1/18, 5.6%), and splenic sequestration (1/18, 5.6%). Technical successes, intra-procedural parameters, hemodynamic and clinical successes, TIPS patencies, adverse events, imaging evaluations, and follow-ups were recorded. Results: All (100%) TIPS placements were successful; however, a direct intrahepatic portosystemic shunt was created in one (5.6%) patient. Mean reduction of the portosystemic shunt gradient was 9.1±3.3 mmHg (range: 4–16 mmHg). Seventeen (94.4%) patients demonstrated clinical success with resolution of their initial clinical indication for TIPS placement. The 3-year TIPS primary, primary-assisted, and secondary patencies were 83.3% (15/18), 94.4% (17/18), and 100% (18/18), respectively. Two (11.1%) patients developed mild, medically controlled hepatic encephalopathy. One (5.6%) patient developed hepatopulmonary syndrome. Nine (50%) patients developed single or multiple hepatic nodules at a mean imaging surveillance time after TIPS of 4.4±3.0 years (range: 1.5–10.2 years). Six (33.3%) patients developed nodules >1 cm with imaging features most consistent with focal nodular hyperplasia or focal nodular hyperplasia-like nodules. The mean follow-up duration was 5.7±2.9 years (range: 3.0–13.1 years). Conclusion: Long-term (>3 years) portosystemic shunting via TIPS is associated with the development of hepatic nodular lesions in children. Consequently, children with TIPS may need gray-scale assessment of hepatic parenchyma as part of routine ultrasound exams and extended imaging surveillance until more is understood regarding the natural history of induced nodularity. [ABSTRACT FROM AUTHOR]

Background: Accurate and reproducible means of measuring the portosystemic gradient are essential for risk stratification and treatment of portal hypertension. Objective: To report the reliability of hepatic venous pressure gradients in children with intrahepatic veno-venous collateralization. Materials and methods: Between January 2012 and December 2019 (96 months), 39 patients with native livers underwent wedge hepatic venography and hepatic venous pressure gradient measurements at a tertiary pediatric center. All archived images were reviewed for balloon isolation of the hepatic vein and hepatic vein-to-hepatic vein (HV-HV) collaterals. HV-HV collaterals were categorized as present on the basis of non-catheterized segmental venous opacification despite appropriate balloon isolation. Hepatic venous pressure gradient was defined as the difference of wedge and free hepatic venous pressures. Wedge portosystemic gradient was defined as the difference between wedge hepatic venous pressure and right atrial (RA) pressures. For patients subsequently undergoing portal venous catheterization, portosystemic gradient was defined as the difference between main portal vein and RA pressures. Results: Thirteen of 39 (33.3%) patients demonstrated HV-HV collaterals on wedge hepatic venography. The mean hepatic venous pressure gradient was 5.2±3.8 mmHg (range: 0–15 mmHg). The mean hepatic venous pressure gradient was 3.6±2.6 mmHg (range: 0–9 mmHg) in the presence of HV-HV collaterals and 5.9±4.2 mmHg (range: 1–15 mmHg) in the absence of HV-HV collaterals (P=0.043). Twelve (30.8%) patients were found to have varices: 10 gastroesophageal, 1 rectal and 1 stomal. The mean hepatic venous pressure gradient in patients with varices was 5.4±47 mmHg (range: 0–15 mmHg). For patients with varices, mean hepatic venous pressure gradient was 3.0±2.7 mmHg (range: 0–9 mmHg) in the presence of HV-HV collaterals and 10.3±4.1 mmHg (range: 5–15 mmHg) in the absence of HV-HV collaterals (P=0.004). Four (10.3%) patients had extrahepatic portal vein occlusion: 3 with cavernous transformation and 1 with type Ib Abernethy malformation. All patients with extrahepatic portal vein occlusion demonstrated HV-HV collaterals compared with 8 of 35 (22.9%) patients without extrahepatic portal vein occlusion (P=0.002). Four of 39 (10.3%) patients underwent direct portal pressure measurements: 3 via transhepatic and 1 via trans-splenic portal access. All had demonstrated HV-HV collaterals on wedged imaging. One had extrahepatic portal vein occlusion. The mean time between wedge portosystemic gradient and portosystemic gradient measurement was 3.75 days (range: 0–8 days). The mean wedge portosystemic gradient was 4.5±3.1 mmHg (range: 2–9 mmHg) and the mean portosystemic gradient was 14.5±3.7 mmHg (range: 12–20 mmHg) (P=0.006). Conclusion: HV-HV collateralization is frequently observed in children undergoing wedged portal venography and leads to misrepresentative hepatic venous pressure gradients. All patients undergoing hepatic venous pressure gradient measurement should have wedged venography to identify HV-HV collaterals and to qualify measured pressures. Additional techniques to obtain representative pressures in the presence of HV-HV collaterals warrant further investigation. [ABSTRACT FROM AUTHOR]

Adult liver transplant programs have heretofore been hesitant to perform liver retransplantation in adult patients who underwent primary liver transplantation as a child (P_A). Areas of concern include: (a) potential disruption in care when transferring from a pediatric to an adult transplant center; (b) generally inferior outcomes of retransplantation; (c) reputation of young adults for non‐adherence to post‐transplant regimen; and (d) potential higher work effort for equivalent outcomes. To examine these concerns, we reviewed data on all US liver adult retransplants from 10/01/1987 to 9/30/2017. We propensity matched the P_A patients to patients who received both primary and retransplantation as adults (A_A), with ≥550 days between transplants. A mixed Cox proportional hazards model with program size and time period of transplantation as random variables revealed that retransplantation of P_A patients produced no significantly different graft survival or patient survival rates than retransplantation of the matched A_A patients. Therefore, inferior rates of liver retransplantation in these patients and concerns about continuity of care in changing transplant programs are not as believed in the wider liver transplant community. In conclusion, liver transplant centers should be optimistic about retransplanting adults who received their primary transplants as children. [ABSTRACT FROM AUTHOR]

Learning Health Networks (LHN) improve the well‐being of populations by aligning clinical care specialists, technology experts, patients and patient advocates, and other thought leaders for continuous improvement and seamless care delivery. A novel LHN focused on pediatric transplantation, the Starzl Network for Excellence in Pediatric Transplantation (SNEPT), convened its inaugural meeting in September 2018. Clinical care team representatives, patients, and patient families/advocates partnered to take part in educational sessions, pain point exercises, and project identification workshops. Participants discussed the global impact of transplant from both a population and individual perspective, identifying challenges and opportunities where the Starzl Network could work to improve outcomes at scale across a variety of transplant‐related conditions. [ABSTRACT FROM AUTHOR]

Introduction: Indications for TIPS are well described in adults and involve complications of PHTN. Complications from PHTN are associated with PSG of > 12 mm Hg in adults. It is unclear if these parameters apply to children with PHTN. Objective: To assess whether adult criteria for TIPS placement can be utilized in children, describe laboratory changes over time, and report outcomes. Methods: We performed a retrospective review of 34 pediatric patients who underwent TIPS, examining indications, radiology, PSG reductions, laboratory changes, and outcomes. Results: Most patients had PHTN due to parenchymal liver disease including congenital hepatic fibrosis (n = 5), biliary atresia (n = 5), cystic fibrosis–related liver disease (n = 3) and cavernous transformation of the portal vein (n = 6). Indications for TIPS included variceal bleeding, recurrent ascites, and maintenance of portal vein flow following thrombolysis. Variceal bleeding was observed in six children with PSG < 12 mm Hg. Minor complications occurred in eight subjects. Continued bleeding occurred in one patient. Six patients were successfully bridged to transplantation, and three patients died secondary to end‐stage disease. Standard laboratory tests stabilized after TIPS placement and hematocrit increased. Conclusion: TIPS placement in pediatric patients was performed for complications of PHTN. Unlike adult series, a substantial proportion of our cases treated extrahepatic PHTN from cavernous transformation of the portal vein. Children presented with sequelae of PHTN with PSG below 12 mm Hg, below the adult standard. We found TIPS in pediatrics to be safe and effective with laboratory stabilization and improvement in hematocrit. [ABSTRACT FROM AUTHOR]

Background: Pediatric liver transplantation for small recipients presents significant challenges, particularly in securing suitably sized donor organs. This case report illustrates the feasibility of performing an in situ split procurement in an 18.5-kg toddler, the smallest recorded case in the OPTN database to date, for a critically ill 8-week-old infant recipient., Case Presentation: An 8-week-old infant with severe hepatitis of unknown etiology was urgently listed as Status 1A. An organ offer from a 3.5-year-old donor, requiring a reduction procedure, became available 1939 nautical miles away. Instead of a back-table reduction procedure, we performed an in situ split to reduce cold ischemic time given the distance. The recipient surgery was started ahead of the organ's arrival, and the recipient was ready for graft implantation upon the organ's arrival, resulting in a total of 510 min of cold ischemic time. Post-operatively, the graft did not show signs of significant injury or dysfunction, which expedited recovery from her other medical conditions., Conclusions: In situ split liver procurement is an invaluable tool for pediatric centers as it effectively provides more graft options for pediatric patients on the waitlist. Additionally, in situ split can offer significant benefits in optimizing recipient surgery, especially when the donor is located at an extreme distance. Despite these benefits, in situ split is not currently widely utilized across transplant centers. Addressing the logistical challenges associated with this technique is crucial for broader implementation and improved patient outcomes., (© 2024 Wiley Periodicals LLC.)

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., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background and Aims: High levels of serum matrix metalloproteinase-7 (MMP-7) have been linked to biliary atresia (BA), with wide variation in concentration cutoffs. We investigated the accuracy of serum MMP-7 as a diagnostic biomarker in a large North American cohort., Approach and Results: MMP-7 was measured in serum samples of 399 infants with cholestasis in the Prospective Database of Infants with Cholestasis study of the Childhood Liver Disease Research Network, 201 infants with BA and 198 with non-BA cholestasis (age median: 64 and 59 days, p = 0.94). MMP-7 was assayed on antibody-bead fluorescence (single-plex) and time resolved fluorescence energy transfer assays. The discriminative performance of MMP-7 was compared with other clinical markers. On the single-plex assay, MMP-7 generated an AUROC of 0.90 (CI: 0.87-0.94). At cutoff 52.8 ng/mL, it produced sensitivity = 94.03%, specificity = 77.78%, positive predictive value = 64.46%, and negative predictive value = 96.82% for BA. AUROC for gamma-glutamyl transferase = 0.81 (CI: 0.77-0.86), stool color = 0.68 (CI: 0.63-0.73), and pathology = 0.84 (CI: 0.76-0.91). Logistic regression models of MMP-7 with other clinical variables individually or combined showed an increase for MMP-7+gamma-glutamyl transferase AUROC to 0.91 (CI: 0.88-0.95). Serum concentrations produced by time resolved fluorescence energy transfer differed from single-plex, with an optimal cutoff of 18.2 ng/mL. Results were consistent within each assay technology and generated similar AUROCs., Conclusions: Serum MMP-7 has high discriminative properties to differentiate BA from other forms of neonatal cholestasis. MMP-7 cutoff values vary according to assay technology. Using MMP-7 in the evaluation of infants with cholestasis may simplify diagnostic algorithms and shorten the time to hepatoportoenterostomy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)