Home-based fecal calprotectin utilization in a general pediatric gastroenterology clinic.

OBJECTIVE: Remote investigation and monitoring have gained importance in ambulatory practice. A home-based fecal calprotectin (FC) test has been developed where the sample is processed and analyzed at home through a smartphone application. We aimed to assess the use of standard ELISA (sFC) versus home-based (hFC) FC testing in a general pediatric gastroenterology clinic. METHODS: Ambulatory pediatric patients with hFC or sFC performed between August 2019 and November 2020 were included. Data regarding demographics, clinical characteristics, medication use, investigations, and final diagnosis, categorized as inflammatory bowel disease (IBD), functional gastrointestinal (GI) disorders, organic non-IBD (ONI) GI disorders, non-GI disorders, and undetermined after 6 months of investigation, were recorded. RESULTS: A total of 453 FC tests from 453 unique patients were included. Of those, 249 (55%) were hFC. FC levels (median) were higher in children with IBD compared to non-IBD diagnosis (sFC 795 vs. 57 µg/g, hFC 595 vs. 47 µg/g, p < 0.001), and in ONI compared to functional GI disorders (sFC 85 vs. 54 µg/g, p = 0.003, hFC 57 vs. 40 µg/g, p < 0.001). No significant difference was observed between different ONI GI disorders or subtypes of functional disorders. Age did not significantly influence levels. CONCLUSIONS: Overall, hFC and sFC provide similar results in the general pediatric GI ambulatory setting. FC is a sensitive but not disease-specific marker to identify patients with IBD. Values appear to be higher in ONI GI disorders over functional disorders, although cut-off values have yet to be determined.

Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis.

BACKGROUND AND AIMS: Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes. APPROACH AND RESULTS: We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis. CONCLUSIONS: We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.

Colorectal Dysplasia and Cancer in Pediatric-Onset Ulcerative Colitis Associated With Primary Sclerosing Cholangitis.

Inflammatory bowel disease (IBD), especially when associated with primary sclerosing cholangitis (PSC), is a risk factor for developing colorectal cancer (CRC).1-3 We aimed to determine the incidence of CRC in a large cohort of pediatric-onset PSC-ulcerative colitis (UC) patients.

Vedolizumab Therapy in Children With Primary Sclerosing Cholangitis: Data From the Pediatric Primary Sclerosing Cholangitis Consortium.

OBJECTIVES: Most patients with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD). The liver and colon express MAdCAM-1, a target of lymphocyte homing integrins. Vedolizumab (VDZ) is an α4ß7 integrin antibody used to treat IBD. We investigated liver outcomes in children with PSC-IBD treated with VDZ. METHODS: Patients were identified within the Pediatric PSC Consortium, a multicenter research registry. Retrospective demographic, phenotypic, biochemical, radiological, histopathologic and IBD data for up to 1 year of VDZ therapy were collected. Liver biochemical and IBD responses were defined as: a 75% or greater reduction in initial γ-glutamyltransferase (GGT), or a GGT that fell to <50 IU/L and improved Mayo endoscopy grade or IBD activity scores after 9 to 12 months. RESULTS: Thirty-seven patients were identified from 19 centers. VDZ was initiated at median age of 16 years [IQR 15-18], 69% were male, 65% had large duct involvement, 19% had (Metavir F3/F4) fibrosis and 59% had ulcerative colitis. Of 32 patients with abnormal GGT at baseline, 22% had a liver biochemical response after 9 to 12 months. For IBD, 32% achieved remission, 30% had a clinical response, and 38% had no response. Final GGT after 9 to 12 months was 51 [IQR 28-71] in IBD patients in remission versus 127 [IQR 63-226] in those with active IBD, (P = 0.066). CONCLUSIONS: Liver biochemistry worsened over time in IBD unresponsive to VDZ but remained unchanged in IBD patients in remission. VDZ did not improve liver biochemistry in pediatric PSC-IBD. Progressive liver disease may be more common in patients with medically refractory IBD.

Similarity Network Fusion: A Novel Application to Making Clinical Diagnoses.

Similarity Network Fusion (SNF) is a novel methodological tool that integrates multiple different types of data to identify homogeneous subsets of patients in whom disease classification may be otherwise unclear or challenging. In this review article, the authors hope to provide insight into how SNF can be used in clinical decision making where the aim is to have little influence on the data prior to obtaining the results of the analysis.

Second-line Agents in Pediatric Patients With Autoimmune Hepatitis: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Ten percent to 20% of children with autoimmune hepatitis (AIH) require second-line therapy to achieve remission. Although current guidelines exist on first-line management, evidence for second-line therapy in treatment-refractory patients is lacking. Our aim was to perform a systematic review and meta-analysis of the efficacy and safety of second-line treatments used in this population. METHODS: Electronic and manual searches were used to identify potential studies for inclusion. Studies were selected based on reported response rates to second-line therapies in children who failed response to prednisone and azathioprine. Data extraction and risk of bias assessment were performed independently by 2 reviewers. Meta-analysis using weighted estimate of response rates at 6 months was performed for each treatment option. Heterogeneity was assessed. RESULTS: Fifteen studies of 76 pediatric patients with AIH were included in the review. Overall response rates at 6 months were estimated as 36% for mycophenolate mofetil (MMF) (N = 34, 95% confidence interval [CI] (16-57)), and 50% for tacrolimus (N = 4, 95% CI (0-100%)) and 83% for cyclosporine (N = 15, 95% CI (66%-100%)). Adverse effects were most frequent with cyclosporine (64% experiencing at least 1 adverse effect) followed by tacrolimus (54%) and MMF (48%). Pooled estimates of adverse events were 78% for cyclosporine (95% CI (54%-100%)), 42% for tacrolimus (95% CI (0%-85%)) and 45% for MMF (95% CI (25%-68%)). Sensitivity analyses were not performed due to small sample size. CONCLUSIONS: Cyclosporine had the highest response rate at 6 months in children with standard-treatment-refractory AIH; however, it also had the highest rate of adverse events. MMF was the second most efficacious option with a low adverse effect rate.

A national retrospective study of paediatric end-stage liver disease as a predictor of change to second-line therapy in children with autoimmune hepatitis.

BACKGROUND & AIMS: Adult studies of autoimmune hepatitis (AIH) have shown that the model of end-stage liver disease is associated with resistance to first-line treatment. Using a multicentre retrospective database, we sought to determine if the paediatric end-stage liver disease (PELD) score would similarly predict treatment resistance in paediatric AIH. METHODS: One hundred and seventy-one children from 13 Canadian centres who fulfilled the International Autoimmune Hepatitis Group (IAIHG) criteria were included and assessed for change to second-line therapy within 24 months of primary treatment onset. Those with PSC overlap at presentation, or missing data on the PELD variables were excluded. PELD was calculated for all remaining patients. Univariate analysis and receiver-operator characteristic (ROC) curves were performed to determine the predictive ability of the PELD score to change to second-line therapy. RESULTS: A total of 103 children were included with median age of 11 years (range 2-17). Mean PELD was -2.51±8.58. Second-line therapy was used within 24 months of diagnosis in 13 patients. Univariate analysis revealed that change to second-line therapy was associated with higher PELD (P=.028) and internal normalized ratio (INR) (P=.011). ROC curves for PELD and its individual components were performed. The strength of association was strongest with INR (AUC 0.72; CI: 0.58-0.86) although the composite PELD score also showed some predictive ability (AUC 0.67; CI: 0.52-0.81). CONCLUSION: In this paediatric AIH cohort, higher PELD at presentation predicted change to second-line therapy within the first 2 years of follow-up. INR appeared to be the main contributor to that association.