Autoimmune Antibodies in Children and Adolescents With Nonalcoholic Fatty Liver Disease.

OBJECTIVES: The clinical significance of autoantibody positivity in nonalcoholic fatty liver disease (NAFLD) in the absence of autoimmune hepatitis (AIH) remains uncertain. We aimed to determine the prevalence of autoantibodies in a pediatric cohort with biopsy-proven NAFLD and investigate the association between autoantibodies and NAFLD histologic grade. METHODS: Single-center, retrospective study of patients ≤21 years with biopsy-proven NAFLD from 2014 to 2019. Clinical and laboratory data were obtained within 90 days of liver biopsy. Autoantibody positivity was defined as serum titer ≥1:80 or units ≥20. Liver biopsies were evaluated for features of AIH, then scored for steatosis, hepatocyte ballooning, lobular inflammation, and NAFLD activity score (NAS) was calculated. Portal inflammation and fibrosis were scored separately. Multivariable logistic regression was used for continuous and binary outcomes. RESULTS: Sixty-seven subjects met inclusion criteria. Positive antinuclear antibody (ANA), antismooth muscle antibody (ASMA), antineutrophil cytoplasmic antibody (ANCA), anti-F-actin antibody (F-actin), anti-liver kidney microsomal (LKM) antibody, or any combination was observed in 43%, 39%, 19%, 13%, 0%, and 66% of subjects, respectively. After controlling for confounders, positive ANA and alanine aminotransferase (ALT) >80 had 4.6 greater odds of having an NAS ≥5 ( P = 0.035; 95% confidence interval [CI], 1.12-19.01). Autoantibody positivity resolution occurred in 10%-50% who underwent serial monitoring. CONCLUSIONS: Autoantibodies, except LKM, were frequently encountered in our pediatric NAFLD cohort in the absence of AIH. ANA positivity with ALT may help clinically stratify pediatric patients with suspected NAFLD targeting those at greater risk for nonalcoholic steatohepatitis (NASH).

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

Content available: Author Audio Recording.

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.

Liraglutide with Lifestyle Intervention in Adolescents with Overweight/Obesity, Nonalcoholic Fatty Liver Disease, and Type II Diabetes Mellitus.

There is a strong interplay between nonalcoholic fatty liver disease (NAFLD), obesity, insulin resistance, and type II diabetes mellitus (T2DM). Liraglutide, a glucagon-like-peptide-1 (GLP-1) analogue, is FDA approved for T2DM in children 10 years or older and more recently approved for chronic weight management in children 12 years or older with obesity. GLP-1 analogues have also been shown to reduce liver enzymes and improve liver histology. We report two adolescent females with T2DM and biopsy proven nonalcoholic steatohepatitis (NASH) refractory to lifestyle intervention who were safety treated with liraglutide with associated weight loss and liver enzyme improvement. This is the first case series reporting use of liraglutide in pediatric NASH. Liraglutide should be considered in pediatric patients with overweight/obesity, NAFLD, and T2DM.

Utilization of Topiramate as an Adjunct to Lifestyle Intervention for Weight Loss in Pediatric Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease is the most common chronic liver disease in children and has become the leading indication for liver transplantation in adults. The primary treatment modality is lifestyle modification to promote weight loss, which is challenging to achieve and maintain. Adjunctive weight loss medications, such as topiramate, are commonly used off-label in adults and children with obesity and found to be safe and effective. We report an adolescent male with severe obesity and nonalcoholic steatohepatitis refractory to aggressive lifestyle intervention. He was safely treated with topiramate with resultant weight loss, reduction in body mass index z-score, improvement in liver enzymes, and resolution of hepatic steatosis. This is the first report of using topiramate in a pediatric patient with obesity and nonalcoholic steatohepatitis. Topiramate should be considered in pediatric nonalcoholic fatty liver disease to help curb emotional eating and promote satiety in cases refractory to lifestyle intervention alone.

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.

Update on childhood/adolescent obesity and its sequela.

PURPOSE OF REVIEW: We aim to describe current concepts on childhood and adolescent obesity with a strong focus on its sequela. Childhood obesity is a national epidemic with increasing prevalence over the past three decades placing children at increased risk for many serious comorbidities, previously felt to be only adult-specific diseases, making this topic both timely and relevant for general pediatricians as well as for subspecialists. RECENT FINDINGS: Childhood obesity develops through an interplay of genetics, environment, and behavior. Treatment includes lifestyle modification, and now metabolic and bariatric surgery is more commonly considered in carefully selected adolescents. The off-label use of adjunct medications for weight loss in childhood and adolescent obesity is still in its infancy, but will likely become the next logical step in those with lifestyle modification refractory obesity. Obesity can lead to several comorbidities, which can persist into adulthood potentially shortening the child's lifespan. SUMMARY: Efforts should be focused primarily on reducing childhood and adolescent obesity, and when indicated treating its sequela in effort to reduce future morbidity and mortality in this precious population. VIDEO ABSTRACT: http://links.lww.com/MOP/A36.