Faculty Bibliography

Liver abnormalities in severe acute respiratory syndrome-coronavirus 2 infection, including hepatitis and cholestasis, have been observed in adults and are associated with worse outcomes. We describe 2 adolescents with cholestasis and hepatitis with mild presentation of severe acute respiratory syndrome-coronavirus 2 lacking typical symptoms. Our intention is to raise index of suspicion for testing and protective equipment use.

Pediatric liver transplant recipients are at risk of developing graft fibrosis which can affect patient survival. VCTE is a non-invasive tool that measures LSM and has been shown to correlate with hepatic fibrosis. The aim of this study was to therefore evaluate the ability of LSM to predict fibrosis in pediatric liver transplant recipients with different graft types. We performed a cross-sectional study evaluating LSM of 28 pediatric liver transplant recipients who underwent a total of 20 liver biopsies within 1 month of LSM. LSM was compared to liver histology as well as graft type: WL or PL. The median LSM of all post-transplant patients was 5.6 kPa (range = 2.7-18.3). There was a statistically significant correlation between LSM and METAVIR fibrosis score (P = .001) and LAF score (P < .001). There was no difference in LSM between graft type (P = .088). The AUROC curve for LSM predicting any significant fibrosis (F ≥ 2) was 0.863. A cutoff value of 7.25 had a sensitivity of 71%, specificity of 100%, NPV of 87%, and PPV of 100% for significant fibrosis. LSM by VCTE is feasible in pediatric liver transplant recipients regardless of graft type. We found a significant correlation between LSM and hepatic fibrosis and established a cutoff value that may help determine which patients warrant further evaluation for graft fibrosis.

BACKGROUND:Children with sickle cell disease (SCD) are at risk of liver injury because of sickle cell hepatopathy and iron overload from chronic transfusions (CT). The authors examine the association between iron overload and liver stiffness measurement (LSM) by vibration controlled transient elastography (VCTE), which has been shown to correlate with fibrosis. METHODS:Patients 21 years of age and less with SCD had VCTE performed; those who received CT underwent magnetic resonance imaging T2* for iron quantification. RESULTS:The authors enrolled 42 patients, 17 (40%) of whom received CT. There was no difference in LSM between patients who underwent CT (5.5±1.5 kPa) and those who did not (5.2±2.3 kPa) (P=0.923). There was no correlation between iron quantification and LSM (r=-0.077, P=0.769). However, children 12 years of age and older had abnormal LSM when compared with a reference range (P=0.013). CONCLUSION:VCTE is a noninvasive technology that is feasible in children with SCD. LSM values were elevated in older children but did not correlate with iron overload, suggesting that fibrosis may not be affected by iron overload alone. Though additional data are needed, LSM may be a useful test for the progression of liver disease in SCD regardless of iron burden.

Health care delivery is increasingly evaluated according to quality measures, yet such measures are underdeveloped for cirrhosis. The Practice Metrics Committee of the American Association for the Study of Liver Diseases was charged with developing explicit process-based and outcome-based measures for adults with cirrhosis. We identified candidate measures from comprehensive reviews of the literature and input from expert clinicians and patient focus groups. We conducted an 11-member expert clinician panel and used a modified Delphi method to systematically identify a set of quality measures in cirrhosis. Among 119 candidate measures, 46 were identified as important measures to define the quality of cirrhosis care, including 26 process measures, 7 clinical outcome measures, and 13 patient-reported outcome measures. The final process measures captured care processes for ascites (n = 5), varices/bleeding (n = 7), hepatic encephalopathy (n = 4), hepatocellular cancer (HCC) screening (n = 1), liver transplantation evaluation (n = 2), and other care (n = 7). Clinical outcome measures included survival, variceal bleeding and rebleeding, early-stage HCC, liver-related hospitalization, and rehospitalization within 7 and 30 days. Patient-reported outcome measures covered physical symptoms, physical function, mental health, general function, cognition, social life, and satisfaction with care. The final list of patient-reported outcomes was validated in 79 patients with cirrhosis from nine institutions in the United States. Conclusion: We developed an explicit set of evidence-based quality measures for adult patients with cirrhosis. These measures are a tool for providers and institutions to evaluate their care quality, drive quality improvement, and deliver high-value cirrhosis care. The quality measures are intended to be applicable in any clinical care setting in which care for patients with cirrhosis is provided.

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.