Alagille Syndrome: A Focused Review on Clinical Features, Genetics, and Treatment.

Alagille syndrome (ALGS) is an autosomal dominant disorder caused by pathogenic variants in JAG1 or NOTCH2, which encode fundamental components of the Notch signaling pathway. Clinical features span multiple organ systems including hepatic, cardiac, vascular, renal, skeletal, craniofacial, and ocular, and occur with variable phenotypic penetrance. Genotype-phenotype correlation studies have not yet shown associations between mutation type and clinical manifestations or severity, and it has been hypothesized that modifier genes may modulate the effects of JAG1 and NOTCH2 pathogenic variants. Medical management is supportive, focusing on clinical manifestations of disease, with liver transplant indicated for severe pruritus, liver synthetic dysfunction, portal hypertension, bone fractures, and/or growth failure. New therapeutic approaches are under investigation, including ileal bile acid transporter (IBAT) inhibitors and other approaches that may involve targeted interventions to augment the Notch signaling pathway in involved tissues.

Early detection of SARS-CoV-2 and other infections in solid organ transplant recipients and household members using wearable devices.

The increasing global prevalence of SARS-CoV-2 and the resulting COVID-19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns, and blood oxygen saturation show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS-CoV-2 is detectable before clinical symptoms in >80% of adults. Early detection of SARS-CoV-2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self-isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS-CoV-2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant-specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS-CoV-2, and other infections are also reviewed.

Genomics and Liver Transplantation: Genomic Biomarkers for the Diagnosis of Acute Cellular Rejection.

Acute cellular rejection (ACR) is a common complication in liver transplantation recipients (LTRs), especially within the first 12 months, and it is associated with increased morbidity and mortality. Although abnormalities in standard liver biochemistries may raise the clinical suspicion for ACR, it lacks specificity, and invasive liver biopsies, which are associated with numerous risks, are required for definitive diagnoses. Biomarker discovery for minimally invasive tools for diagnosis and prognostication of ACR after liver transplantation (LT) has become a rapidly evolving field of research with a recent shift in focus to omics-based biomarker discovery. Although none are yet ready to replace the standard of care, there are several promising minimally invasive, blood-derived biomarkers that are under intensive research for the diagnosis of ACR in LTRs. These omics-based biomarkers, encompassing DNA, RNA, proteins, and metabolites, hold tremendous potential. Some are likely to become integrated into ACR diagnostic algorithms to assist clinical decision making with a high degree of accuracy that is cost-effective and reduces or even obviates the need for an invasive liver biopsy.

Patient perspective on exercise practices, preferences, and barriers in pediatric nonalcoholic fatty liver disease: A multicenter survey.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is prevalent among children, and lifestyle modification is the primary treatment approach. However, the optimal exercise duration, frequency, and intensity for managing NAFLD remain undefined. This study aimed to gain insights from the patient perspective by examining exercise behaviors, preferences, and barriers in children with NAFLD. Methods: A multicenter survey was conducted among children 8-18 years with NAFLD in pediatric gastroenterology clinics. Participants completed a questionnaire on exercise practices, preferences, and barriers, while parents completed a questionnaire on their willingness and ability to support their child's exercise. Data were analyzed using χ 2 test with Yates' correction and two-sample t test. Results: The study included 408 children with NAFLD, with a mean age of 13.8 years. Approximately 52.5% of participants had physical education classes at school, while 59.5% engaged in extracurricular exercise, averaging 3.7 days per week. However, 11.5% reported no physical activity. A significant majority (81.1%) expressed interest in increasing their exercise levels, primarily driven by health-related factors. Time-related constraints were the most cited barriers to exercise (53.7%). Approximately 80% of parents demonstrated willingness and ability to support their child's exercise regimen. Conclusion: This study provides insights into exercise behaviors, preferences, and barriers among children with NAFLD. Half of the children lacked exercise opportunities at school but expressed interest in increasing their physical activity. Time limitation was the major obstacle cited. Parents are motivated to support increased physical activity. Exercise intervention programs for NAFLD should consider the perspective of the children and their families.

Live Vaccines in Pediatric Liver Transplant Recipients: "To Give or Not to Give".

Content available: Author Audio Recording.