Faculty Bibliography

One cause of neonatal cholestasis (NC) is paucity of intrahepatic bile ducts which can be associated with Alagille syndrome or non- syndromic. Alagille syndrome is caused by autosomal dominant mutations in the Notch signaling pathway ligand Jagged1 in 94% of patients and mutations in the NOTCH2 receptor in <1% of patients. This is a retrospective case series studying infants with neonatal cholestasis found to have variants of unknown significance (VOUS) in NOTCH2. Sorting intolerant from tolerant (SIFT) and polymorphism phenotyping (PolyPhen) were utilized to predict a damaging effect. Five infants with NC without other features of Alagille syndrome were found to have one copy of a VOUS in NOTCH2, predicted to be damaging by SIFT and PolyPhen. Our cases support the notion that NOTCH2 mutations may result in hypoplastic biliary system. Further characterization of these variants is important to assist with our clinical approach to NC.

Benign biliary strictures are uncommon in children. Classically, these cases are managed surgically, however less invasive approaches with interventional radiology and or endoscopy may have similar results and improved safety profiles While benign biliary strictures have been described in literature on several occasions in young children, (most older than 1 year and once in an infant 3 months of age), all reported cases were managed surgically. We present two cases of benign biliary strictures in infants less than 6 months of age that were managed successfully with novel non-invasive procedures and a review of all current pediatric cases reported in the literature. Furthermore, we describe the use of a Rendezvous procedure, which has not been reported as a treatment approach for benign biliary strictures.

OBJECTIVE:There are multiple approaches to manage the clinical complications of portal hypertension (PHTN) to treat/prevent spontaneous hemorrhage by mitigating thrombocytopenia. No single approach is ideal for all patients given the heterogeneity of this population. Our goal was to determine whether partial splenic embolization (PSE) was safe and effective in the pediatric population. METHODS:This is a retrospective review of our single-center experience for all patients ages 0 to 21 who underwent PSE between January 2010 and August 2017. The embolized splenic volume targeted was 60% to 70%. RESULTS:Twenty-six patients underwent PSE due to thrombocytopenia and/or recurrent variceal bleeding. Patients ranged in age from 18 months to 20 years (mean 13.1 years). The median platelet count before PSE was 53.0 (×10/L). The platelet count improved after PSE with values >100,000 in 21 patients (80.8%). Children with prior esophageal varices showed improvement after PSE with only 9 (34.6%) requiring further endoscopic therapy. After PSE, patients developed transient abdominal pain, distention, fever, and perisplenic fluid collections. Serious complications such as splenic abscess, splenic rupture, bleeding, pancreatic infarction, opportunistic infection, or death were not observed. One patient experienced thrombotic complications after PSE and was later diagnosed with myelodysplastic syndrome. CONCLUSIONS:PSE is a safe and effective alternative in the management of pediatric PHTN in select populations. PSE may be a favorable alternative to splenectomy and portal systemic shunting because it preserves functional spleen mass and avoids postprocedure accelerated liver disease or encephalopathy.

Some patients with veno-occlusive disease (VOD) have multiorgan dysfunction, and multiple teams are involved in their daily care in the pediatric intensive care unit. Cardiorespiratory dysfunction is critical in these patients, requiring immediate action. The decision of whether to use a noninvasive or an invasive ventilation strategy may be difficult in the setting of mucositis or other comorbidities in patients with VOD. Similarly, monitoring of organ functions may be very challenging in these patients, who may have fulminant hepatic failure with or without hepatic encephalopathy complicated by delirium and/or infections. In this final guideline of our series on supportive care in patients with VOD, we address some of these questions and provide evidence-based recommendations on behalf of the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplantation Consortium Joint Working Committees.

UNLABELLED:Patients with cirrhosis seek improvement in their symptoms, functioning, quality of life, and satisfaction with the care they receive. However, these patient-reported outcomes (PROs) are not routinely measured for clinical care, research, or quality improvement. The members of the American Association for the Study of Liver Diseases Practice Metrics Committee, charged with developing quality indicators for clinical practice, performed a scoping review of PROs in cirrhosis. The aim is to synthesize a comprehensive set of PROs for inclusion into a standard patient-centered outcome set. We searched Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and the Cochrane Trial Library since inception, with final searches run between April 20 and June 1, 2017. Studies were included if they reported the construction and/or validation of a PRO instrument for patients with cirrhosis or if they assessed the clinical (case-mix) variables determining responses to established PRO scales. Eleven studies were selected that yielded 259 items specific to patients with cirrhosis. After removing duplicates, 152 unique items were isolated. These items were consolidated into seven domains: physical symptoms, physical function, mental health, general function, cognition, social life, and satisfaction with care. The seven domains included 52 subdomains (e.g., physical domain, abdominal pain subdomain). Twelve variables were identified that independently modified established PRO scales. These included clinical factors (severity of liver disease and its complications, medication burden, and comorbidities), specific PROs (cramps, pruritis), and surrogate outcome measures (falls, hospitalization). CONCLUSION:This scoping review identified and categorized a large existing set of PRO concepts that matter to patients with cirrhosis; these outcomes may now be translated into usable measures both for the assessment of the quality of cirrhosis care in clinical practice and to perform research from the patient's perspective. (Hepatology 2018;67:2375-2383).

BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and is the most common liver disease in the developed world. In children with suspected NAFLD, present guidelines suggest consideration of alternative diagnoses via extensive blood testing, though the yield of this work up is unknown. Furthermore, the gold standard diagnostic test for NAFLD remains liver biopsy, making the development of non-invasive tests critically important. OBJECTIVES:Our objectives are: 1) to determine the accuracy of elastography and multiple serum biomarkers - each assessed individually and as algorithms (including those previously tested in adults) - for the diagnosis of nonalcoholic steatohepatitis (NASH) and early fibrosis in children and (2) to examine the utility of extensive testing for rare alternative diagnoses in overweight or obese children with elevated alanine aminotransferase (ALT) suspected to have NAFLD. DESIGN:This is an ongoing, cross-sectional study in children 2-18 years of age with up to 2 years of prospective follow up. Eligible patients are asymptomatic, overweight or obese, and have an ALT ≥35 U/L upon enrollment. Two forms of elastography are obtained serially along with anthropometric data and routine laboratory tests. Elastography and serum biomarkers are also performed immediately prior to any clinically-indicated biopsy. METHODS:Between April 2015 and April 2018, 193 children have been enrolled in this ongoing study and 71 have undergone liver biopsy. Here we carefully report the rationale, methodology, and preliminary data for this study.