Risk factors for more rapid progression of severe liver fibrosis in children with cystic fibrosis-related liver disease: A multi-center study validated by liver biopsy.

BACKGROUND AND AIMS: Early identification of risk factors for the development of severe fibrosis in children with cystic fibrosis-related liver disease (CFLD) is crucial as promising therapies emerge. METHODS: This multi-center cohort study of children with a priori defined CFLD from 1999 to 2016, was designed to evaluate the clinical utility of CF-specific characteristics and liver biomarkers assessed years prior to liver biopsy-proven CFLD to predict risk of developing severe fibrosis (F3-4) over time. Fibrosis was staged by Metavir classification. RESULTS: The overall study cohort of 42 patients (F0-2 (n = 22) and F3-4 (n = 20)) was 57% male (n = 24) with median age of 7.6 years at baseline visit versus 10.3 years at biopsy. Median FEV1 % predicted was lower in F3-4 participants at baseline versus F0-2 (59% vs. 85%; p = .002), while baseline FIB-4, APRI and GGT were higher in F3-4. Median splits for FIB-4 (≥.13), APRI (≥.36), GPR (≥.09), GGT (≥25.5), and FEV1 % (<64%) were associated with more rapid progression to F3-4 (p < .01 for all). Using a combination of change/year in FIB-4, APRI, and GPR to predict F3-4, the AUROC was .81 (95% CI, .66, .96; p < .0001). For up to 5.8 years prior, thresholds for GPR were met 6.5-fold more rapidly, and those for APRI and FIB-4 were met 2.5-fold more rapidly, in those who progressed to F3-4 than those that did not. CONCLUSIONS: This study suggests mild-moderate pulmonary dysfunction and higher liver biomarker indices at baseline may be associated with faster progression of CFLD.

Impact of psychosocial factors on medication level variability index and outcomes in pediatric liver transplant recipients.

BACKGROUND: Caregivers play an important role in maintaining a functioning graft after pediatric liver transplantation. Therefore, the psychosocial factors of both patients and caregivers can have a critical impact on transplant outcomes. Appropriate assessment and recognition of these factors pre-transplantation may allow transplant teams to better define the needs of pediatric organ recipients and develop specific countermeasures, which may then contribute toward improving transplant outcomes. METHODS: We studied 136 pediatric LT recipients followed at Texas Children's Hospital. Licensed social workers conducted comprehensive pre-transplant assessments on each patient, consisting of 22 psychosocial variables that were thought to impact adherence, which were reviewed during our study period. Non-adherence was determined using the MLVI for up to 4 years after transplantation. Biopsy-confirmed rejection episodes were assessed in the first 3 years after liver transplantation. RESULTS: Factors significantly associated with non-adherence (defined as MLVI >2) included parental age and parental education level at assessment, type of insurance, and household income. The number of ACR episodes trended higher in patients with non-adherence, and these patients had a higher number of moderate to severe rejection episodes but this trend was not statistically significant. CONCLUSIONS: Psychosocial characteristics such as parental age, education level, insurance, and household income may contribute significantly to suboptimal adherence to medications after transplantation. Identification of these psychosocial factors and early intervention is essential to the success and equitable care of our pediatric LT recipients.

Rolling stones: an instructive case of neonatal cholestasis.

BACKGROUND: Jaundice within the first 1-2 weeks of a neonate's life will generally self-resolve; however, if it lasts longer than this time frame it warrants further work up. Direct or conjugated hyperbilirubinemia can suggest neonatal cholestasis, which in turn reflects marked reduction in bile secretion and flow. The differential diagnosis for neonatal cholestasis is broad. Neonatal choledocholithiasis is a rare cause of neonatal cholestasis, but should be considered on the differential diagnosis for patients presenting with elevated conjugated bilirubin. CASE PRESENTATION: We describe an infant who presented with neonatal cholestasis. He subsequently underwent work up for biliary atresia, as this is one of the more time-sensitive diagnoses that must be made in neonates with conjugated hyperbilirubinemia. He was ultimately found to have choledocholithiasis on magnetic resonance cholangiopancreatography. He was managed conservatively with optimizing nutrition and ursodeoxycholic acid therapy. CONCLUSIONS: We found that conservative management, specifically optimizing nutrition and treating with ursodeoxycholic acid, can be a sufficient approach to facilitating resolution of the choledocholithiasis and conjugated hyperbilirubinemia.

Progression of pediatric celiac disease from potential celiac disease to celiac disease: a retrospective cohort study.

BACKGROUND: A subset of patients with serology suggesting celiac disease have an initially negative biopsy but subsequently develop histopathologic celiac disease. Here we characterize patients with potential celiac disease who progress to celiac disease. METHODS: We performed a retrospective analysis of children (0-18 years of age) with biopsy-confirmed celiac disease seen at St. Louis Children's Hospital between 2013 and 2018. RESULTS: Three hundred sixteen of 327 (96%) children with biopsy-confirmed celiac disease were diagnosed on initial biopsy. The 11 children with potential celiac disease who progressed to celiac disease had lower anti-tissue transglutaminase (anti-TTG IgA) concentrations (2.4 (1.6-5) X upper limit of normal (ULN) vs. 6.41 (3.4-10.5) X ULN) at time of first biopsy. Their median anti-TTG IgA concentrations rose from 2.4 (1.6-5) X ULN to 3.6 (3.1-9.2) X ULN between biopsies. CONCLUSIONS: Four percent of biopsy confirmed celiac patients initially had a negative biopsy, but later developed histopathologic celiac disease. This is likely an underestimate as no surveillance algorithm was in place. We recommend repeat assessment in children whose serology suggests celiac disease despite normal small bowel biopsy.

Adherence to surgical antibiotic prophylaxis remains a challenge despite multifaceted interventions.

BACKGROUND: Adherence to prophylactic antibiotics guidelines is challenging and poorly documented. We hypothesized that a multiphase, multifaceted quality improvement initiative would engage relevant stakeholders, address known barriers to adoption, and improve overall adherence. METHODS: From 2011 to 2014, a series of interventions were introduced in the pediatric operating rooms. After each interventional period, prospective assessments were performed to record the antibiotic type, dose, timing, and redosing according to the guidelines. Perioperative factors that may influence guideline adherence were analyzed. Spearman's rank correlation, analysis of variance, and χ(2) tests were performed. RESULTS: A total of 1,052 operations were observed, and 629 (60%) required prophylactic antibiotics. Adherence to all 4 guideline components remained unchanged (54-55%, P = .38). Redosing significantly improved (7-53%, P = .02), but correct type decreased (98-70%, P < .01). The percentage of cases in which only one antibiotic guideline component was missed remained unchanged (35-34%, P = .46). Adherence to guidelines was not significantly associated with American Society of Anesthesiologists class, surgical specialty, patient weight, anesthesia provider, or surgical wound class. CONCLUSION: Despite multiple interventions to improve antibiotic prophylaxis, overall adherence did not improve. Most interventions were directed at the point of administration in the operating room; future implementation strategies should focus on the perioperative setting.