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Background and aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. Approach and results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced >= 1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and = 5.0 and = 10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those 10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to = 5.0 mg/dl, with 79% reaching adulthood with native liver (p < 0.001). Conclusions: in this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB, This study received funding support from the following agencies: The Alagille Syndrome Alliance, Mirum Pharmaceuticals Inc. and Albireo Pharma, Inc. who provided unrestricted educational grants to the Hospital for Sick Children (SickKids Foundation). The study sponsors were not involved in the conduct of the research study or preparation of the manuscript.

Background Children with inflammatory bowel disease [IBD] are disproportionally affected by recurrent Clostridioides difficile infection [rCDI]. Although faecal microbiota transplantation [FMT] has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in paediatric IBD. Methods We performed a retrospective review of FMT at 20 paediatric centres in the USA from March 2012 to March 2020. Children with and without IBD were compared with determined differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared with determined predictors of success. Safety data and IBD-specific outcomes were obtained. Results A total of 396 paediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort [76% vs 81%, p = 0.17]. Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool [p = 0.03], were without diarrhoea prior to FMT [p = 0.03], or had a shorter time from rCDI diagnosis until FMT [p = 0.04]. Children with a failed FMT were more likely to have clinically active IBD post-FMT [p = 0.002] and 19 [13%] patients had an IBD-related hospitalisation in the 3-month follow-up. Conclusions Based on the findings from this large US multicentre cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.

BACKGROUND & AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis. APPROACH & RESULTS: A targeted ELISA-based panel of 9 biomarkers (lysyl oxidase (LOX), tissue inhibitor matrix metalloproteinase 1 (TIMP1), connective tissue growth factor (CTGF), interleukin-8 (IL-8), endoglin, periostin, mac-2-binding protein (mac2-BP), matrix metalloproteinase-3 and −7 (MMP-3, MMP-7) was examined in children with biliary atresia (BA, n=187), alpha-1 antitrypsin deficiency (A1AT, n=78) and Alagille syndrome (ALGS, n=65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations between LSM and endoglin (p=0.04), IL-8 (p

Fecal microbiota transplant and dermatologic disorders: A retrospective cohort study assessing the gut microbiome’s role in skin disease

BACKGROUND Around 1800 pediatric transplantations were performed in 2021, which is approximately 5% of the annual rate of solid organ transplantations carried out in the United States. Effective family self-management in the transition from hospital to home-based recovery promotes successful outcomes of transplantation. The use of mHealth to deliver self-management interventions is a strategy that can be used to support family self-management for transplantation recipients and their families. OBJECTIVE The study aims to evaluate the acceptability of an mHealth intervention (myFAMI) that combined use of a smartphone app with triggered nurse communication with family members of pediatric transplantation recipients. METHODS This is a secondary analysis of qualitative data from family members who received the myFAMI intervention within a larger randomized controlled trial. Eligible participants used the app in the 30-day time frame after discharge and participated in a 30-day postdischarge telephone interview. Content analysis was used to generate themes. RESULTS A total of 4 key themes were identified: (1) general acceptance, (2) positive interactions, (3) home management after hospital discharge, and (4) opportunities for improvement. CONCLUSIONS Acceptability of the intervention was high. Family members rated the smartphone application as easy to use. myFAMI allowed the opportunity for families to feel connected to and engage with the medical team while in their home environment. Family members valued and appreciated ongoing support and education specifically in this first 30 days after their child’s hospital discharge and many felt it contributed positively to the management of their child’s medical needs at home. Family members provided recommendations for future refinement of the app and some suggested that a longer follow-up period would be beneficial. The development and refinement of mHealth care delivery strategies hold potential for improving outcomes for solid organ transplantation patients and their families and as a model to consider in other chronic illness populations. CLINICALTRIAL ClinicalTrials.gov NCT03533049; https://clinicaltrials.gov/ct2/show/NCT03533049

Approximately 50% of infants with biliary atresia (BA) undergoing Kasai portoenterostomy show survival with native liver (SNL) at age 2 years. Predictors of disease progression after age 2 years are unknown, despite estimates of 20%‐30% undergoing liver transplant (LT) between age 2 and 18 years. We sought to address this knowledge gap by developing prognostic models in participants of the multicenter prospective National Institutes of Health‐supported Childhood Liver Disease Research Network. We extracted 14 clinical and biochemical variables at age 2 years to develop two models for future outcomes: 1) LT or death (LTD) and 2) first sentinel event (SE), either new onset ascites, hepatopulmonary syndrome (HPS), or gastrointestinal (GI) bleed. A total of 240 participants, enrolled between 2004 and 2017, were followed until a median age of 5.1 years (range, 2.0‐13.3 years). Of these participants, 38 underwent LT (n = 37) or death (n = 1); cumulative incidence, 23.7% (95% confidence interval [CI], 16.2%‐32.0%). Twenty‐seven experienced either new‐onset ascites (n = 13), HPS (n = 1), or GI bleed (n = 14). One participant had ascites and GI bleed concurrently; cumulative incidence, 21.5% (95% CI, 14.2%‐29.8%) by age 10 years. The Cox proportional hazard model predicted risk of LTD, using total bilirubin, albumin, platelet count, and history of either ascites or cholangitis (BA LTD model), with a C‐index of 0.88 (range, 0.86‐0.89). A cause‐specific hazard competing risk model predicted SE using platelet count and gamma glutamyltransferase levels (BA SE model) with a C‐index of 0.81 (range, 0.80‐0.84). Internal model validity was assessed using Harrell’s C‐index with cross‐validation. Conclusion: Stratification using these models identified risk of poor outcomes in patients with BA SNL after age 2 years. The models may identify those who would benefit from enhanced clinical surveillance and prioritization in clinical trials.

The natural history of gastroesophageal variceal hemorrhage (VH) in biliary atresia (BA) is not well characterized. We analyzed risk factors, incidence, and outcomes of VH in a longitudinal multicenter study.Participants enrolled in either an incident (Prospective Database of Infants with Cholestasis [PROBE]) or prevalent (Biliary Atresia Study of Infants and Children [BASIC]) cohort of BA were included. Variceal hemorrhage (VH) was defined based on gastrointestinal bleeding in the presence of varices accompanied by endoscopic or nontransplant surgical intervention. Cumulative incidence of VH and transplant-free survival was compared based on features of portal hypertension (e.g., splenomegaly, thrombocytopenia) and clinical parameters at baseline in each cohort (PROBE: 1.5 to 4.5 months after hepatoportoenterostomy [HPE]; BASIC: at enrollment3 years of age). Analyses were conducted on 869 children with BA enrolled between June 2004 and December 2020 (521 in PROBE [262 (51%) with a functioning HPE] and 348 in BASIC). The overall incidence of first observed VH at 5 years was 9.4% (95% CI: 7.0-12.4) in PROBE and 8.0% (5.2-11.5) in BASIC. Features of portal hypertension, platelet count, total bilirubin, aspartate aminotransferase (AST), albumin, and AST-to-platelet ratio index at baseline were associated with an increased risk of subsequent VH in both cohorts. Transplant-free survival at 5 years was 45.1% (40.5-49.6) in PROBE and 79.2% (74.1-83.4) in BASIC. Two (2.5%) of 80 participants who had VH died, whereas 10 (12.5%) underwent transplant within 6 weeks of VH.The low risk of VH and associated mortality in children with BA needs to be considered in decisions related to screening for varices and primary prophylaxis of VH.

Fecal microbiota transplant for more than Clostridioides difficile: Dermatology a new frontier

Primary sclerosing cholangitis (PSC) is a rare disease of stricturing and destruction of the biliary tree with a complex genetic and environmental etiology. Most patients have co-occurring inflammatory bowel disease. Children generally present with uncomplicated disease, but undergo a variable progression to end-stage liver disease. Within ten years of diagnosis, 50% of children will develop clinical complications including 30% requiring liver transplantation. Cholangiocarcinoma is a rare but serious complication affecting 1% of children. Ursodeoxycholic acid and oral vancomycin therapy used widely in children as medical therapy, and may be effective in a subset of patients. Gamma glutamyltransferase is a potential surrogate endpoint for disease activity, with improved survival in patients who achieve a normal value. Endoscopic retrograde cholangiopancreatography is a necessary adjunct to medical therapy to evaluate mass lesions or dominant strictures for malignancy, and also to relieve biliary obstruction. Liver transplantation remains the only option for patients who progress to end-stage liver disease. We review special considerations for patients before and after transplant, and in patients with inflammatory bowel disease. There is presently no published treatment algorithm or guideline for the management of children with PSC. We review the evidence for drug efficacy, dosing, duration of therapy, and treatment targets in PSC, and provide a framework for endoscopic and medical management of this complex problem.

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.

Background and Aims: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. Approach and Results: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of

BACKGROUND/PURPOSE: Meckel diverticulum (MD) is present in 2% of the population. Many practitioner feel the diagnosis relies upon technetium-99m pertechnetate scintigraphy. When negative, patients undergo additional invasive procedures delaying definitive therapy. This study aims to identify features of bleeding MD and generate a risk score, which could preclude unnecessary testing and facilitate earlier operation. METHODS: All patients

Background & Aims Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI. Methods We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT. Results Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39–5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26–4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05–4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04–1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations. Conclusions Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients—factors associated with success differ from those of adult patients.

OBJECTIVEClostridium difficile infection (CDI) places a high burden on the US healthcare system. Recurrent CDI (RCDI) occurs frequently. Recently proposed guidelines from the American College of Gastroenterology (ACG) and the American Gastroenterology Association (AGA) include fecal microbiota transplantation (FMT) as a therapeutic option for RCDI. The purpose of this study was to estimate the cost-effectiveness of FMT compared with vancomycin for the treatment of RCDI in adults, specifically following guidelines proposed by the ACG and AGA.DESIGNWe constructed a decision-analytic computer simulation using inputs from the published literature to compare the standard approach using tapered vancomycin to FMT for RCDI from the third-party payer perspective. Our effectiveness measure was quality-adjusted life years (QALYs). Because simulated patients were followed for 90 days, discounting was not necessary. One-way and probabilistic sensitivity analyses were performed.RESULTSBase-case analysis showed that FMT was less costly ($1,669 vs $3,788) and more effective (0.242 QALYs vs 0.235 QALYs) than vancomycin for RCDI. One-way sensitivity analyses showed that FMT was the dominant strategy (both less expensive and more effective) if cure rates for FMT and vancomycin were ≥70% and CONCLUSIONSOur results suggest that FMT may be a cost-saving intervention in managing RCDI. Implementation of FMT for RCDI may help decrease the economic burden to the healthcare system.Infect Control Hosp Epidemiol 2014;00(0): 1–7

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC–inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. Conclusion: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC–inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518–527).

Neonatal cholestasis results from a variety of etiologies, including anatomic, infectious, and metabolic abnormalities. Hyperthyroidism, in contrast to hypothyroidism, is infrequently associated with neonatal cholestasis. Newborn screening is an important tool to detect newborn metabolic disorders, including thyroid dysfunction. However, one must exercise caution when interpreting these reports; typically only high thyroid stimulating hormone (TSH) levels are flagged as abnormal, while low or undetectable levels may not be. We present a unique case of cholestasis in a hyperthyroid neonate of an untreated, undiagnosed mother with Graves' disease; the infant's metabolic screen was not flagged as abnormal.

The epidemiology and natural history of pediatric primary sclerosing cholangitis (PSC), autoimmune sclerosing cholangitis (ASC), and autoimmune hepatitis (AIH) are not well characterized. Using multiple, overlapping search strategies followed by a detailed records review, we identified all cases of pediatric PSC, ASC, AIH, and inflammatory bowel disease (IBD) in a geographically isolated region of the United States. We identified 607 cases of IBD, 29 cases of PSC, 12 cases of ASC, and 44 cases of AIH. The mean age at diagnosis was 13.0 years for PSC, 11.3 years for ASC, and 9.8 years for AIH. The incidence and prevalence of PSC, ASC, and AIH were 0.2 and 1.5 cases, 0.1 and 0.6 cases, and 0.4 and 3.0 cases per 100,000 children, respectively. The mean duration of follow-up was 5.9 years. The probability of developing complicated liver disease within 5 years of the diagnosis of liver disease was 37% [95% confidence interval (CI) = 21%-58%] for PSC, 25% (95% CI = 7%-70%) for ASC, and 15% (95% CI = 7%-33%) for AIH. The 5-year survival rates with the native liver were 78% (95% CI = 54%-91%) for PSC, 90% (95% CI = 47%-99%) for ASC, and 87% (95% CI = 71%-95%) for AIH. Cholangiocarcinoma developed in 2 of the 29 PSC patients (6.9%). PSC occurred in 9.9% of patients with ulcerative colitis (UC) and in 0.6% of patients with Crohn's disease (CD). ASC occurred in 2.3% of UC patients and 0.9% of CD patients. AIH occurred in 0.4% of UC patients and in 0.3% of CD patients. Liver disease occurred in 39 of 607 IBD patients (6.4%) overall. Conclusion: Immune-mediated liver diseases are important sources of morbidity in children. Using a population-based design, this study quantifies the burden and natural history of immune-mediated liver disease in children. (Hepatology 2013;58:1392–1400)

Portal vein thrombosis (PVT) occurs in ≤12% of pediatric recipients of liver transplantation (LT). Known complications of PVT include portal hypertension, allograft loss, and mortality. The management of PVT is varied. A single-center, case-control study of pediatric LT recipients with portal vein (PV) changes after LT was performed. Cases were categorized as early PVT (if PVT was detected within 30 days of transplantation) or late PVT (if PVT was detected more than 30 days after transplantation or if early PVT persisted beyond 30 days). Two non-PVT control patients were matched on the basis of the recipient weight, transplant indication, and allograft type to each patient with PVT. Thirty-two of the 415 LT recipients (7.7%) received 37 allografts and developed PVT. In comparison with control patients, a higher proportion of patients with PVT had PVT present before LT (13.3% versus 0%, P = 0.01). Patients with early PVT usually returned to the operating room, and 9 of 15 patients (60%) had PV flow restored. Patients with late PVT had lower white blood cell (4.9 [1000/μL] versus 6.8 [1000/μL], P < 0.01) and platelet counts (140 [1000/μL] versus 259 [1000/μL], P < 0.01), an elevated international normalized ratio (1.2 versus 1.0, P < 0.001), and more gastrointestinal bleeding (25% versus 8.3%, P = 0.03) compared to controls. Patients with PVT were also less frequently at the expected grade level (52% versus 88%, P < 0.001). The patient survival rates were 84%, 78%, and 78% and 91%, 84%, and 79% for cases and controls at 1, 5, and 10 years, respectively. The allograft survival rates were 90%, 80%, and 80% for cases and 94%, 89%, and 87% for controls at 1, 5, and 10 years, respectively. In conclusion, patients with early and late PVT had preserved allograft function, and there was no impact on mortality. Patients diagnosed with early PVT often underwent operative interventions with successful restoration of flow. Patients diagnosed with late PVT experienced variceal bleeding, and some required portosystemic shunting procedures. Academic delays were also more common. In late PVT, the clinical presentation dictates care because the optimal management algorithm has not yet been determined. Multi-institutional studies are needed to confirm these findings and improve patient outcomes. Liver Transpl 19:315–321, 2013. © 2013 AASLD.

Background & Aims Celiac disease is detected using serology and endoscopy analyses. We used multiple statistical analyses of a geographically isolated population in the United States to determine whether a single serum screening can identify individuals with celiac disease. Methods We performed a retrospective study of 3555 pediatric patients (18 years old or younger) in the intermountain West region of the United States from January 1, 2008, through September 30, 2013. All patients had undergone serologic analyses for celiac disease, including measurement of antibodies to tissue transglutaminase (TTG) and/or deamidated gliadin peptide (DGP), and had duodenal biopsies collected within the following year. Modified Marsh criteria were used to identify patients with celiac disease. We developed models to identify patients with celiac disease using logistic regression and classification and regression tree (CART) analysis. Results Single use of a test for serum level of IgA against TTG identified patients with celiac disease with 90% sensitivity, 90% specificity, a 61% positive predictive value (PPV), a 90% negative predictive value, and an area under the receiver operating characteristic curve value of 0.91; these values were higher than those obtained from assays for IgA against DGP or IgG against TTG plus DGP. Not including the test for DGP antibody caused only 0.18% of celiac disease cases to be missed. Level of TTG IgA 7-fold the upper limit of normal (ULN) identified patients with celiac disease with a 96% PPV and 100% specificity. Using CART analysis, we found a level of TTG IgA 3.2-fold the ULN and higher to most accurately identify patients with celiac disease (PPV, 89%). Multivariable CART analysis showed that a level of TTG IgA 2.5-fold the ULN and higher was sufficient to identify celiac disease in patients with type 1 diabetes (PPV, 88%). Serum level of IgA against TTG in patients with versus those without trisomy 21 did not affect diagnosis predictability in CART analysis. Conclusions In a population-based study, we found that serum level of IgA against TTG can identify patients with celiac disease with PPVs of about 90%. Predictive values increase greatly when levels are markedly above the ULN or when the assay is used in combination with other variables. Measurement of IgG against TTG or DGP does not increase the accuracy of detection of celiac disease based against TTG IgA levels. There is a low risk of false-positive results from serologic analysis in patients with type I diabetes or persistent increases in antibody against TTG on repeat testing.

Historically, HIDA is the initial diagnostic test in the evaluation of biliary atresia (BA). Non-excreting HIDA scans can yield false-positive results leading to negative laparotomy. Cholestatic infants must be evaluated promptly to exclude biliary atresia (BA) and other treatable hepatic conditions. Intraoperative cholangiogram (IOC) is the gold standard for diagnosing BA, but requires surgical intervention. Percutaneous transhepatic cholecysto-cholangiography (PTCC) and liver biopsy are less invasive and have been described in small case series. We hypothesized that PTCC and liver biopsy effectively exclude BA, thus avoiding unnecessary IOC. Retrospective review of cholestatic infants who underwent PTCC, biopsy or cholescintigraphy at a tertiary children’s hospital from August 1998 to January 2009. Group differences were evaluated and the receiver operator curve and safety of PTCC determined. One-hundred twenty-eight cholestatic infants were reviewed. Forty-six (36%) underwent PTCC. Forty-one out of 46 (89%) had simultaneous PTCC and liver biopsy. PTCC was completed successfully in 19/23 (83%) children despite a small or absent GB on initial US. Negative laparotomy rate was 1/6 (17%) for simultaneous PTCC/liver biopsy. Complications occurred in 4/46 including bleeding (n = 2), fever with elevated transaminases (n = 1) and oxygen desaturations (n = 1). PTCC, particularly when performed in combination with simultaneous liver biopsy, effectively excludes BA in cholestatic infants with acceptable morbidity. PTCC can frequently be performed when a contracted gallbladder is seen on initial US exam. Negative laparotomy rate is lowest when PTCC is coupled with simultaneous liver biopsy.

Background CDI is a common cause of bacterial diarrhea, especially in immunocompromised patients. Fecal Microbiota Transplanation (FMT) has been shown to be an effective treatment for recurrent and refractory CDI. The outcomes of FMT treatment for recurrent CDI have been well described in adult populations; however, the data for immunocompromised (IC) patients especially among children are limited. We describe the experience of FMT for treatment of CDI in immuncompromised pediatric patients. Methods We collected clinical data for IC patients Results We performed 37 pediatric FMT for recurrent, refractory, and/or severe CDI between September 2012 and February 2017. Of these, 12 were immunocompromised children: 2 with SOT; 3 with neoplasm and/or HSCT; and 7 with IBD on immunosuppressive medication(s). Median age was 11.9 years old (range 3–16 years). 6 (50%) experienced resolution of diarrhea within 1 week post-FMT, and 9 (67%) were C. difficile negative within 3 months of FMT (3 patients did not have follow-up testing). None had CDI relapse within 3 months post-FMT. 3 (25%) had adverse event(s) within 3 months post-FMT, 2 of whom had SAEs: 1 had graft rejection at 2 months post-FMT which ultimately required re-transplantion and 1 had aspiration pneumonitis immediately following FMT. 4 (50%) of the IBD patients had disease remission (clinical, biologic, and/or histologic) in the 3 months post-FMT. Conclusion FMT appears to be effective and reasonably safe for recurrent CDI in immunocompromised pediatric patients. However, the small numbers limit conclusions, especially about safety. Larger multicenter studies are needed to precisely determine safety and efficacy in this specialized population. Disclosures All authors: No reported disclosures.

Limited data on short- and long-term outcomes of renal replacement therapy (RRT) in pediatric liver transplantation (LT) patients exist. We evaluated risk factors for RRT in pediatric LT recipients with hepatorenal syndrome (HRS) and described the outcomes. We performed a single-center, case-control study of LT recipients who required RRT for HRS from 1999 to 2011. Three controls who did not receive RRT were matched with each case on the basis of age, diagnosis, and LT date. We identified 8 recipients among 133 recipients of 152 LT cases [6%, 95% confidence interval = 2%-10%; mean age = 7.7 years, range = 0.5-19.8 years) who required RRT before LT for HRS. Four patients were 0.99; and 97 versus 114 mL/minute/1.73 m2 at the most recent follow-up, P = 0.09). The case survival rates were 75% and 63% at 1 month and 1 year, respectively; 4 cases required antihypertensives and diuretics 1 month after LT, but at the last follow-up, only 1 case required antihypertensive therapy, and none required diuretics. In conclusion, pediatric patients with HRS, including infants, benefit from RRT. Although HRS decreases survival, patients with HRS who undergo LT generally recover renal function within 1 month that persists during long-term follow-up.

Limited data on short- and long-term outcomes of renal replacement therapy (RRT) in pediatric liver transplantation (LT) patients exist. We evaluated risk factors for RRT in pediatric LT recipients with hepatorenal syndrome (HRS) and described the outcomes. We performed a single-center, case-control study of LT recipients who required RRT for HRS from 1999 to 2011. Three controls who did not receive RRT were matched with each case on the basis of age, diagnosis, and LT date. We identified 8 recipients among 133 recipients of 152 LT cases [6%, 95% confidence interval = 2%-10%; mean age = 7.7 years, range = 0.5-19.8 years) who required RRT before LT for HRS. Four patients were1 year old and weighed 5.6 to 6.6 kg. Biliary atresia was the most common LT indication. Cases had higher Model for (Pediatric) End-Stage Liver Disease scores at listing (26 versus 16, P = 0.01) and lower glomerular filtration rates (GFRs; 15 versus 102 mL/minute/1.73 m(2) , P 0.001) at RRT initiation or LT. Ascites, gastrointestinal bleeding, and infections occurred more commonly among cases: (100% versus 54%, P = 0.03; 100% versus 46%, P = 0.01; and 88% versus 33%, P = 0.01, respectively). Cases also experienced toxic vancomycin troughs more frequently (38% versus 0%, P = 0.01) and received RRT for a median of 21 days (range = 3-355 days). The case mortality rate was 37.5% (3/8 at 1, 26, and 346 days after LT) and 0% for controls. The 4 infants required 0 to 3 dialysis catheter replacements during RRT. Cases and controls had similar median follow-ups [3.2 years (range = 1.5-7.6 years) versus 4.9 years (range = 0.2-11 years), P = 0.29]. After LT, they also had similar GFRs (83 versus 99 mL/minute/1.73 m(2) at 1 month, P = 0.19; 80 versus 107 mL/minute/1.73 m2 at 1 year, P 0.99; and 97 versus 114 mL/minute/1.73 m2 at the most recent follow-up, P = 0.09). The case survival rates were 75% and 63% at 1 month and 1 year, respectively; 4 cases required antihypertensives and diuretics 1 month after LT, but at the last follow-up, only 1 case required antihypertensive therapy, and none required diuretics. In conclusion, pediatric patients with HRS, including infants, benefit from RRT. Although HRS decreases survival, patients with HRS who undergo LT generally recover renal function within 1 month that persists during long-term follow-up.

Objective To assess sustained immunosuppression-free remission (SIFR) in children with autoimmune hepatitis (AIH). Study design We retrospectively reviewed all children with AIH in the region between 1986 and 2011 using a population-based methodology. Results We identified 56 children with AIH (62.5% females; median age, 11.1 years [IQR, 5.7-14.4 years], followed for a median of 5.6 years [IQR, 2.8-8.6 years]). Liver disease was characterized by type II AIH in 8.9%, cirrhosis in 14.0%, and primary sclerosing cholangitis in 21.4%. Coexisting nonhepatic immune-mediated diseases occurred in 37.5%. Biochemical remission on immunosuppressive therapy was achieved in 76.4% of all patients with AIH at a median of 1.2 years (IQR, 0.4-3.6 years); 23.1% of these patients experienced a subsequent relapse. Discontinuation of all immunosuppressive medications was attempted in 16 patients and was successful in 14 patients (87.5%) with type 1 AIH (median age at discontinuation, 8.9 years [IQR, 3.5-17.9 years], treated for a median of 2.0 years [IQR, 1.3-3.5 years] after diagnosis), with SIFR occurring at a median of 3.4 years (IQR, 2.6-5.8 years) of follow-up. Excluding patients with inflammatory bowel disease who received immunosuppressive therapy independent of their liver disease, the probability of achieving SIFR within 5 years of diagnosis of AIH was 41.6% (95% CI, 25.3%-62.9%). Baseline patient characteristics associated with an inability to achieve biochemical remission on immunosuppression or SIFR were elevated international normalized ratio, positive antineutrophil cytoplasmic antibody titer, cirrhosis, and a nonhepatic autoimmune disorder. Conclusion We found a high rate of successful discontinuation of all immunosuppressive medications in carefully selected patients with AIH in a population-based cohort. SIFR is an achievable goal for children with AIH, particularly those with type I disease in stable biochemical remission on immunosuppressive therapy.

Portal vein thrombosis (PVT) occurs in ≤12% of pediatric recipients of liver transplantation (LT). Known complications of PVT include portal hypertension, allograft loss, and mortality. The management of PVT is varied. A single-center, case-control study of pediatric LT recipients with portal vein (PV) changes after LT was performed. Cases were categorized as early PVT (if PVT was detected within 30 days of transplantation) or late PVT (if PVT was detected more than 30 days after transplantation or if early PVT persisted beyond 30 days). Two non-PVT control patients were matched on the basis of the recipient weight, transplant indication, and allograft type to each patient with PVT. Thirty-two of the 415 LT recipients (7.7%) received 37 allografts and developed PVT. In comparison with control patients, a higher proportion of patients with PVT had PVT present before LT (13.3% versus 0%, P = 0.01). Patients with early PVT usually returned to the operating room, and 9 of 15 patients (60%) had PV flow restored. Patients with late PVT had lower white blood cell (4.9 [1000/μL] versus 6.8 [1000/μL], P0.01) and platelet counts (140 [1000/μL] versus 259 [1000/μL], P0.01), an elevated international normalized ratio (1.2 versus 1.0, P0.001), and more gastrointestinal bleeding (25% versus 8.3%, P = 0.03) compared to controls. Patients with PVT were also less frequently at the expected grade level (52% versus 88%, P0.001). The patient survival rates were 84%, 78%, and 78% and 91%, 84%, and 79% for cases and controls at 1, 5, and 10 years, respectively. The allograft survival rates were 90%, 80%, and 80% for cases and 94%, 89%, and 87% for controls at 1, 5, and 10 years, respectively. In conclusion, patients with early and late PVT had preserved allograft function, and there was no impact on mortality. Patients diagnosed with early PVT often underwent operative interventions with successful restoration of flow. Patients diagnosed with late PVT experienced variceal bleeding, and some required portosystemic shunting procedures. Academic delays were also more common. In late PVT, the clinical presentation dictates care because the optimal management algorithm has not yet been determined. Multi-institutional studies are needed to confirm these findings and improve patient outcomes.

Background and objectives Acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in the first 100 days following allogeneic hematopoietic progenitor stem cell transplant. The best diagnostic endoscopic strategy for gastrointestinal (GI) GVHD is a matter of debate. Our aim in the present study was to compare the relative contribution of the endoscopic appearance and biopsies from upper endoscopy and flexible sigmoidoscopy in children with suspected acute GVHD. Methods The present study was designed as single-center retrospective chart review cohort study. We reviewed the charts of all of the patients younger than 18 years with suspected acute GI GVHD who had endoscopic evaluation within the first 100 days after stem cell transplant between 1999 and 2009. Results A total of 48 patients were included. The most common symptoms prompting endoscopic evaluation were diarrhea (70%) and a combination of nausea and vomiting (67%). GVHD was diagnosed in at least 1 biopsy site in 40 of 48 patients (83%). Twenty-two of 40 (55%) patients with GVHD had simultaneous upper and lower endoscopic biopsies, 11 patients had only upper endoscopy, and 7 had only lower endoscopy. The most common endoscopic finding was normal mucosa. The sensitivity for diagnosing GVHD was 77% for both rectosigmoid and upper endoscopic biopsies. Thirty-three of 40 patients had upper endoscopy with biopsies; 28 (85%) had GVHD. The sensitivities and negative predictive value of gastric biopsies were 85% and 63%, whereas for duodenal biopsies they were 50% and 57%, respectively. Conclusions Rectosigmoid and combined upper endoscopic biopsies are equally sensitive for the diagnosis of acute GI GVHD in children. Flexible sigmoidoscopy can be done unsedated in appropriate patients at the bedside without anesthesia; it can be performed first to identify GI GVHD.

Background Capsule endoscopy (CE) is used increasingly to evaluate the small bowel in children. An upper GI series is recommended before CE to evaluate the risk of obstruction. Despite normal findings on an upper GI series, CE may still be incomplete. Although large adult studies have demonstrated the safety and diagnostic yield of CE, similar pediatric studies have not been available. Objective To identify factors associated with incomplete studies and the diagnostic yield in pediatric patients. Design Retrospective review of consecutive CE studies from February 2005 through June 2008. Setting Large tertiary children's hospital. Patients A total of 123 CE studies in 117 patients; median age 12.9 years (range 0.8-22.4 years). Main Outcome Measurements Demographic information, indication, placement technique, pre-CE imaging results, and cecal completion status were recorded. Risk factors were analyzed with bivariate and multivariate regression analysis. Results There were 27 (22%) incomplete studies; of these, there were normal pre-CE radiologic study findings in 12 (44%), and findings requiring medical, endoscopic, or operative intervention in 6. Of the 117 patients, CE produced a new diagnosis in 21 (18%). Abnormal findings on previous imaging (odds ratio [OR] 3.0; 95% CI, 1.2-8.0), endoscopic placement (OR 3.1; 95% CI, 1.1-8.4), and female sex (OR 3.3; 95% CI, 1.2-9.4) were associated with incomplete studies. Limitations Retrospective, incomplete follow-up. Conclusions CE may be performed in children as small as 11.5 kg, with 18% yield in all studies, and 28% in pediatric known inflammatory bowel disease. Capsule retention requiring retrieval did not pose life-threatening risk in our series, and CE may be used to identify disease-associated small-bowel stenosis.