Publications by authors named "Pamela L Valentino"

30 Publications

  • Page 1 of 1

North American biliary stricture management strategies in children post liver transplant: multicenter analysis from the SPLIT Registry.

Liver Transpl 2021 Nov 27. Epub 2021 Nov 27.

Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Background: Biliary strictures affect 4-12% of pediatric liver transplants (P-LT). Biliary strictures can contribute to graft loss if left untreated, however there remains no consensus on the best course of treatment. Study objectives included analyses of outcomes associated with biliary stricture management strategies via PTC, ERCP or surgery.

Methods: We identified P-LT recipients (2011-2016) with biliary strictures from the Society of Pediatric Liver Transplantation (SPLIT) registry and retrieved imaging, procedural and operative reports from individual centers. Sub-analyses were performed to specifically evaluate PTC and ERCP for "Optimal Biliary Outcome" (OBO), defined as survival with stricture resolution without recurrence or surgery.

Results: 113 children with median 3.9 years of follow-up had strictures diagnosed 100 days (IQR 30, 290) post LT; 81% were isolated anastomotic strictures. Stricture resolution was achieved in 92% within 101 days, more frequently with isolated anastomotic strictures (96%). 20% of strictures recurred, more commonly in association with hepatic artery thrombosis (32%). Patient and graft survival at 1- and 3-years were 99%, 98% and 94%, 92% respectively. In a subgroup analysis of 79 patients with extrahepatic strictures managed by PTC/ERCP: 59% achieved OBO following a median 4 PTC, and 75% following a median 3 ERCP (P=0.0003). Among patients with OBO, those with ERCP had longer time intervals between successive procedures (41, 47, 54, 62, 71 days) than for PTC (27, 31, 36, 41, 48 days; P=0.0006).

Conclusions: Allograft salvage was successful across all interventions. Stricture resolution was achieved in 92%, with 20% risk of recurrence. Resolution without recurrence was highest in patients with isolated anastomotic strictures and without HAT.
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http://dx.doi.org/10.1002/lt.26379DOI Listing
November 2021

Alternative Etiologies of Liver Disease in Children With Suspected NAFLD.

Pediatrics 2021 04;147(4)

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;

Objectives: To determine the prevalence of alternative causes of liver disease in a cohort of youth with overweight and obesity undergoing evaluation for suspected nonalcoholic fatty liver disease (NAFLD).

Methods: Multicenter, retrospective cohort study of patients aged ≤18 years with overweight and obesity and evidence of elevated serum aminotransferases and/or hepatic steatosis on imaging, referred for suspected NAFLD to Cincinnati Children's Hospital Medical Center (2009-2017) or Yale New Haven Children's Hospital (2012-2017). Testing was performed to exclude the following: autoimmune hepatitis (AIH), Wilson disease, viral hepatitis (B and C), thyroid dysfunction, celiac disease, α-1 antitrypsin deficiency, and hemochromatosis.

Results: A total of 900 children with overweight and obesity (63% boys, 26% Hispanic ethnicity) were referred, with a median age of 13 years (range: 2-18). Most had severe obesity ( = 666; 76%) with a median BMI score of 2.45 (interquartile range [IQR]: 2.2-2.7). Median alanine aminotransferase level at presentation was 64 U/L (IQR: 42-95). A clinically indicated liver biopsy was performed in 358 children (40%) at a median of 6 months (IQR: 1-14) post initial visit; of those, 46% had confirmed nonalcoholic steatohepatitis. Positive autoantibodies were observed in 13% of the cohort, but none met criteria for AIH. Only 19 (2%) were found to have other causes of liver disease, with no cases of viral hepatitis or Wilson disease detected.

Conclusions: In a large, multicenter cohort, the vast majority of children with overweight and obesity with presumed or confirmed NAFLD tested negative for other causes of liver disease. In contrast to a previous pediatric report, no patient was diagnosed with AIH.
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http://dx.doi.org/10.1542/peds.2020-009829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015155PMC
April 2021

Severe Acute Respiratory Syndrome Coronavirus-2 Infection in Children With Liver Transplant and Native Liver Disease: An International Observational Registry Study.

J Pediatr Gastroenterol Nutr 2021 06;72(6):807-814

Medical College of Wisconsin, Milwaukee, WI.

Objective: Increased mortality risk because of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry.

Methods: In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020.

Results: Patients with LD were more likely to require admission (70% vs 43% LT, P = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, P = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and 1 patient died. Bivariable logistic-regression analysis found that patients with nonalcoholic fatty LD (NAFLD) (odds ratio [OR] 5.6, P = 0.02) and LD (OR 6.1, P = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death).

Conclusions: Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.
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http://dx.doi.org/10.1097/MPG.0000000000003077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183254PMC
June 2021

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

Hepatology 2021 03;73(3):1061-1073

Massachusetts General Hospital, Harvard Medical School, Boston, MA.

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.
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http://dx.doi.org/10.1002/hep.31560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557636PMC
March 2021

Fontan-Associated Liver Disease: Screening, Management, and Transplant Considerations.

Circulation 2020 08 10;142(6):591-604. Epub 2020 Aug 10.

Department of Gastroenterology, Liver Care Center, Children's Mercy Kansas City, MO (R.F.).

Surgical innovation and multidisciplinary management have allowed children born with univentricular physiology congenital heart disease to survive into adulthood. An estimated global population of 70 000 patients have undergone the Fontan procedure and are alive today, most of whom are <25 years of age. Several unexpected consequences of the Fontan circulation include Fontan-associated liver disease. Surveillance biopsies have demonstrated that virtually 100% of these patients develop clinically silent fibrosis by adolescence. As they mature, there are increasing reports of combined heart-liver transplantation resulting from advanced liver disease, including bridging fibrosis, cirrhosis, and hepatocellular carcinoma, in this population. In the absence of a transplantation option, these young patients face a poor quality of life and overall survival. Acknowledging that there are no consensus guidelines for diagnosing and monitoring Fontan-associated liver disease or when to consider heart transplantation versus combined heart-liver transplantation in these patients, a multidisciplinary working group reviewed the literature surrounding Fontan-associated liver disease, with a specific focus on considerations for transplantation.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.045597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422927PMC
August 2020

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

J Pediatr Gastroenterol Nutr 2020 10;71(4):459-464

University of Utah and Intermountain Primary Children's Hospital, Salt Lake City, UT.

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 α4β7 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.
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http://dx.doi.org/10.1097/MPG.0000000000002855DOI Listing
October 2020

Impact of Acuity Circles on Outcomes for Pediatric Liver Transplant Candidates.

Transplantation 2020 08;104(8):1627-1632

Department of Pediatrics, University of Washington, Seattle, WA.

Background: In December 2018, United Network for Organ Sharing approved an allocation scheme based on recipients' geographic distance from a deceased donor (acuity circles [ACs]). Previous analyses suggested that ACs would reduce waitlist mortality overall, but their impact on pediatric subgroups was not considered.

Methods: We applied Scientific Registry of Transplant Recipients data from 2011 to 2016 toward the Liver Simulated Allocation Model to compare outcomes by age and illness severity for the United Network for Organ Sharing-approved AC and the existing donor service area-/region-based allocation schemes. Means from each allocation scheme were compared using matched-pairs t tests.

Results: During a 3-year period, AC allocation is projected to decrease waitlist deaths in infants (39 versus 55; P < 0.001), children (32 versus 50; P < 0.001), and teenagers (15 versus 25; P < 0.001). AC allocation would increase the number of transplants in infants (707 versus 560; P < 0.001), children (677 versus 547; P < 0.001), and teenagers (404 versus 248; P < 0.001). AC allocation led to decreased median pediatric end-stage liver disease/model for end-stage liver disease at transplant for infants (29 versus 30; P = 0.01), children (26 versus 29; P < 0.001), and teenagers (26 versus 31; P < 0.001). Additionally, AC allocation would lead to fewer transplants in status 1B in children (97 versus 103; P = 0.006) but not infants or teenagers. With AC allocation, 77% of pediatric donor organs would be allocated to pediatric candidates, compared to only 46% in donor service area-/region-based allocation (P < 0.001).

Conclusions: AC allocation will likely address disparities for pediatric liver transplant candidates and recipients by increasing transplants and decreasing waitlist mortality. It is more consistent with federally mandated requirements for organ allocation.
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http://dx.doi.org/10.1097/TP.0000000000003079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319877PMC
August 2020

A Low ω-6 to ω-3 PUFA Ratio (n-6:n-3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth.

J Nutr 2020 09;150(9):2314-2321

Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA.

Background: Recent literature suggests that the Western diet's imbalance between high ω-6 (n-6) and low ω-3 (n-3) PUFA intake contributes to fatty liver disease in obese youth.

Objectives: We tested whether 12 wk of a low n-6:n-3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response.

Methods: In a single-arm unblinded study, obese youth 9-19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n-6:n-3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann-Whitney U test, and covariance pattern modeling were used.

Results: Twenty obese adolescents (median age: 13.3 y; IQR: 10.5-16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time.

Conclusions: These data suggest that, independently of weight loss, a low n-6:n-3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype.This trial was registered at clinicaltrials.gov as NCT01556113.
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http://dx.doi.org/10.1093/jn/nxaa183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467848PMC
September 2020

Significance of autoantibody seropositivity in children with obesity and non-alcoholic fatty liver disease.

Pediatr Obes 2021 01 8;16(1):e12696. Epub 2020 Jul 8.

Section of Gastroenterology and Hepatology, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.

Background: Autoantibodies are frequently positive in adults with nonalcoholic fatty liver disease (NAFLD) without concurrent autoimmune hepatitis (AIH). The clinical significance of this is unknown in children.

Objective: To determine the prevalence of autoantibody positivity in pediatric NAFLD and to evaluate its association with disease severity.

Methods: Multicenter, retrospective study of patients ≤18 years of age with biopsy-confirmed NAFLD. Descriptive statistics were used and groups were compared using Wilcoxon-Mann Whitney or χ testing, and multivariable logistic regression was used for binary or ordinal outcomes.

Results: One hundred and thirty six patients with a median age of 14 years were included. The median body mass index Z-score was 2.5 (interquartile range 2.2, 2.6). Positive antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver-kidney microsomal antibody, or any combination of autoantibodies were observed in 22%, 14%, 0%, and 33% of patients, respectively. The proportion of patients with a steatosis score ≥2 was significantly higher in those with positive ANA (P = .045). In the multivariable regression analysis, positive ANA was associated with increased odds of steatosis score ≥2 (odds ratio, 5.91; 95% confidential interval, 1.50-23.26), after controlling for potential confounders. No other significant histology differences were seen between the groups.

Conclusions: Positive ANA and ASMA are common in children with NAFLD; however, anti-LKM positivity is not. ANA positivity is associated with more severe steatosis.
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http://dx.doi.org/10.1111/ijpo.12696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006542PMC
January 2021

Pre-operative screening for biliary atresia in cholestatic infants: A case for percutaneous liver biopsy.

J Pediatr Surg 2020 08 3;55(8):1677. Epub 2020 Jun 3.

Division of Pediatric Surgery, Department of Surgery, Yale University, New Haven, CT. Electronic address:

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http://dx.doi.org/10.1016/j.jpedsurg.2020.04.024DOI Listing
August 2020

The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children.

Hepatology 2021 03 19;73(3):1074-1087. Epub 2020 Dec 19.

Boston Children's Hospital and Harvard Medical School, Boston, MA.

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 <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well.

Conclusions: The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.
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http://dx.doi.org/10.1002/hep.31393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557635PMC
March 2021

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

Clin Gastroenterol Hepatol 2021 05 29;19(5):1067-1070.e2. Epub 2020 Apr 29.

Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.

Inflammatory bowel disease (IBD), especially when associated with primary sclerosing cholangitis (PSC), is a risk factor for developing colorectal cancer (CRC). We aimed to determine the incidence of CRC in a large cohort of pediatric-onset PSC-ulcerative colitis (UC) patients.
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http://dx.doi.org/10.1016/j.cgh.2020.04.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788582PMC
May 2021

Management of Wilson Disease Diagnosed in Infancy: An Appraisal of Available Experience to Generate Discussion.

J Pediatr Gastroenterol Nutr 2020 05;70(5):547-554

Departments of Medicine and Surgery, Section of Digestive Diseases and Transplantation and Immunology, Yale University School of Medicine, New Haven, CT.

Increased access to molecular genetic testing is changing the demographics for diagnosing inherited disorders and imposing new challenges for medical management. Wilson disease (WD), typically diagnosed in older children and adults, can now be detected in utero and in infants (children younger than 24 months, including neonates) via genetic testing. An evidence-based approach to management of these neonates and extremely young children, who are typically asymptomatic, has been hampered by lack of clinical experience. We present a case of an infantile diagnosis of WD, review available experience, and discuss current trends in antenatal genetic testing of parents and fetus that may lead to a very early diagnosis of WD. Based on physiological and nutritional considerations, we propose an algorithmic approach to management of infantile WD as a starting point for further discussion. Future collaboration amongst specialists is essential to identify evidence-based approaches and best practice for managing treatment of infants with genetically diagnosed WD.
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http://dx.doi.org/10.1097/MPG.0000000000002608DOI Listing
May 2020

Progressive Splenomegaly and Hypersplenism: An Unusual Case of Splenic Vein Stenosis with Histologic Findings of Hepatoportal Sclerosis.

J Pediatr 2020 03 20;218:222-227.e1. Epub 2019 Dec 20.

Department of Pediatrics, Section of Pediatric Gastroenterology and Hepatology, Yale University School of Medicine, New Haven, CT.

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http://dx.doi.org/10.1016/j.jpeds.2019.11.018DOI Listing
March 2020

Assessing the Validity of Adult-derived Prognostic Models for Primary Sclerosing Cholangitis Outcomes in Children.

J Pediatr Gastroenterol Nutr 2020 01;70(1):e12-e17

University of Rochester Medical Center, Rochester, NY.

Background: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC.

Methods: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic.

Results: Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy.

Conclusions: All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.
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http://dx.doi.org/10.1097/MPG.0000000000002522DOI Listing
January 2020

Frequency of whole-organ in lieu of split-liver transplantation over the last decade: Children experienced increased wait time and death.

Am J Transplant 2019 11 24;19(11):3114-3123. Epub 2019 Jun 24.

Department of Surgery, Transplant, Primary Children's Hospital, Salt Lake City, Utah.

Organ shortage is a barrier to liver transplantation (LT). Split LT (SLT) increases organ utilization, saving 2 recipients. A simulation of Organ Procurement and Transplantation Network/United Network for Organ Sharing data (2007-2017) was performed to identify whole-organ LT grafts (WLT) that met the criteria for being splittable to 2 recipients. Waitlist consequences presented. Deceased donor (DD) livers transplanted as whole organs were evaluated for suitability to split. Of these DD organs, we identified the adolescent and adult recipients of WLT who were suitable for SLT. Pediatric candidates suitable to share the SLT were ascertained from DD match-run lists, and 1342 splittable DD organs were identified; 438 WLT recipients met the criteria for accepting a SLT. Review of the 438 DD match-run lists identified 420 children next on the list suitable for SLT. Three hundred thirty-three children (79%) underwent LT, but had longer wait-times compared to 591 actual pediatric SLT recipients (median 147 days vs 44 days, P  < 0.001). Thirty-three of 420 children died on waitlist after a mean 206 days (standard deviation 317). Sharing organs suitable for splitting increases the number of LT, saving more lives. With careful patient selection, SLT will not be a disadvantage to the adult recipients. With a children-first allocation scheme, SLT will naturally increase the number of allografts because adult organs are too large for small children.
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http://dx.doi.org/10.1111/ajt.15481DOI Listing
November 2019

Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course.

J Pediatr 2019 06 14;209:92-96.e1. Epub 2019 Mar 14.

Department of Pediatrics, University of Utah, Salt Lake City, UT.

Objective: To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis.

Study Design: We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level <50 IU/L without experiencing portal hypertensive or dominant stricture events, liver transplantation, or death during the first year.

Results: We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not.

Conclusions: Less than one-half of the patients treated with UDCA have a complete GGT normalization in the first year after diagnosis, but this subset of patients has a favorable 5-year outcome. Normalization is less likely in patients with a Crohn's disease phenotype or a laboratory profile suggestive of more advanced hepatobiliary fibrosis. Patients who do not achieve normalization could reasonably stop UDCA, as they are likely not receiving clinical benefit. Alternative treatments with improved efficacy are needed, particularly for patients with already-advanced disease.
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http://dx.doi.org/10.1016/j.jpeds.2019.01.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535363PMC
June 2019

The Impact of Increased Allocation Priority for Children Awaiting Liver Transplant: A Liver Simulated Allocation Model (LSAM) Analysis.

J Pediatr Gastroenterol Nutr 2019 04;68(4):472-479

Department of Pediatrics, University of Washington, Seattle, WA.

Objective: The aim of the study was to investigate the impact of prioritizing infants, children, adolescents, and the sickest adults (Status 1) for deceased donor livers. We compared outcomes under two "SharePeds" allocation schema, which prioritize children and Status 1 adults for national sharing and enhanced access to pediatric donors or all donors younger than 35 years, to outcomes under the allocation plan approved by the Organ Procurement and Transplant Network in December 2017 (Organ Procurement and Transplantation Network [OPTN] 12-2017).

Methods: The 2017 Liver Simulated Allocation Model and Scientific Registry of Transplant Recipients data on all US liver transplant candidates and liver offers 7/2013 to 6/2016 were used to predict waitlist deaths, transplants, and post-transplant deaths under the OPTN 12-2017 and SharePeds schema.

Results: Prioritizing national sharing of pediatric donor livers with children (SharePeds 1) would decrease waitlist deaths for infants (<2 years, P = 0.0003) and children (2-11 years, P = 0.001), with no significant change for adults (P = 0.13). Prioritizing national sharing of all younger than 35-year-old deceased donor livers with children and Status 1A adults (SharePeds 2) would decrease waitlist deaths for infants, children, and all Status 1A/B patients (P < 0.0001 for each). SharePeds 1 and 2 would increase the number of liver transplants done in infants, children, and adolescents compared to the OPTN-2017 schema (P < 0.00005 for all age groups). Both SharePeds schema would increase the percentage of pediatric livers transplanted into pediatric recipients.

Conclusions: Waitlist deaths could be significantly decreased, and liver transplants increased, for children and the sickest adults, by prioritizing children for pediatric livers and with broader national sharing of deceased donor livers.
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http://dx.doi.org/10.1097/MPG.0000000000002287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428603PMC
April 2019

Gamma Glutamyltransferase Reduction Is Associated With Favorable Outcomes in Pediatric Primary Sclerosing Cholangitis.

Hepatol Commun 2018 Nov 25;2(11):1369-1378. Epub 2018 Sep 25.

University of Rochester Medical Center Rochester NY.

Adverse clinical events in primary sclerosing cholangitis (PSC) happen too slowly to capture during clinical trials. Surrogate endpoints are needed, but no such validated endpoints exist for children with PSC. We evaluated the association between gamma glutamyltransferase (GGT) reduction and long-term outcomes in pediatric PSC patients. We evaluated GGT normalization (< 50 IU/L) at 1 year among a multicenter cohort of children with PSC who did or did not receive treatment with ursodeoxycholic acid (UDCA). We compared rates of event-free survival (no portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or liver-related death) at 5 years. Of the 287 children, mean age of 11.4 years old, UDCA was used in 81% at a mean dose of 17 mg/kg/day. Treated and untreated groups had similar GGT at diagnosis (314 versus 300, = not significant [NS]). The mean GGT was reduced at 1 year in both groups, with lower values seen in treated (versus untreated) patients (99 versus 175, = 0.002), but 5-year event-free survival was similar (74% versus 77%, = NS). In patients with GGT normalization (versus no normalization) by 1 year, regardless of UDCA treatment status, 5-year event-free survival was better (91% versus 67%, < 0.001). Similarly, larger reduction in GGT over 1 year (> 75% versus < 25% reduction) was also associated with improved outcome (5-year event-free survival 88% versus 61%, = 0.005). A GGT < 50 and/or GGT reduction of > 75% by 1 year after PSC diagnosis predicts favorable 5-year outcomes in children. GGT has promise as a potential surrogate endpoint in future clinical trials for pediatric PSC.
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http://dx.doi.org/10.1002/hep4.1251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211333PMC
November 2018

Biliary drainage as treatment for allograft steatosis following liver transplantation for PFIC-1 disease: A single-center experience.

Pediatr Transplant 2018 06 14;22(4):e13184. Epub 2018 Apr 14.

Department of Surgery, Section of Transplantation and Immunology, Yale University School of Medicine, New Haven, CT, USA.

Development of macrovesicular steatosis post-LT in patients with PFIC-1 is increasingly being observed, with the etiology not fully understood. We highlight successful and effective EBD for reversal of allograft steatosis in 2 patients with PFIC-1 disease and discuss our experience with internal biliary diversion in this patient population.
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http://dx.doi.org/10.1111/petr.13184DOI Listing
June 2018

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

J Pediatr Gastroenterol Nutr 2017 07;65(1):6-15

*The Hospital for Sick Children †University of Toronto, Toronto, Ontario, Canada ‡Yale University School of Medicine, New Haven, CT §Mount Sinai Hospital, Toronto ||London Health Sciences Centre, Western University, London, Ontario, Canada.

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.
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http://dx.doi.org/10.1097/MPG.0000000000001530DOI Listing
July 2017

The natural history of primary sclerosing cholangitis in 781 children: A multicenter, international collaboration.

Hepatology 2017 08 26;66(2):518-527. Epub 2017 Jun 26.

Texas Children's Hospital, Houston, TX, and Phoenix Children's Hospital, Phoenix, AZ.

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).
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http://dx.doi.org/10.1002/hep.29204DOI Listing
August 2017

Hepatic Issues and Complications Associated With Inflammatory Bowel Disease: A Clinical Report From the NASPGHAN Inflammatory Bowel Disease and Hepatology Committees.

J Pediatr Gastroenterol Nutr 2017 04;64(4):639-652

*Division of Pediatric Gastroenterology and Nutrition, Golisano Children's Hospital, University of Rochester, Rochester, NY †Division of Pediatric Gastroenterology, University of Utah, Salt Lake City ‡Division of Pediatric General and Thoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH §Division of Pediatric Gastroenterology and Hepatology, Seattle Children's Hospital, Seattle, WA ||Division of Pediatric Gastroenterology, Stanford Children's Health, Palo Alto, CA ¶Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH #Section of Pediatric Gastroenterology and Hepatology, Yale University School of Medicine, New Haven, CT **Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA ††Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia ‡‡Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA §§Division of Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, University of Toronto, Toronto, Canada.

Hepatobiliary disorders are common in patients with inflammatory bowel disease (IBD), and persistent abnormal liver function tests are found in approximately 20% to 30% of individuals with IBD. In most cases, the cause of these elevations will fall into 1 of 3 main categories. They can be as a result of extraintestinal manifestations of the disease process, related to medication toxicity, or the result of an underlying primary hepatic disorder unrelated to IBD. This latter possibility is beyond the scope of this review article, but does need to be considered in anyone with elevated liver function tests. This review is provided as a clinical summary of some of the major hepatic issues that may occur in patients with IBD.
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http://dx.doi.org/10.1097/MPG.0000000000001492DOI Listing
April 2017

The Natural History of Primary Sclerosing Cholangitis in Children: A Large Single-Center Longitudinal Cohort Study.

J Pediatr Gastroenterol Nutr 2016 12;63(6):603-609

Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA.

Objectives: Data regarding pediatric primary sclerosing cholangitis (PSC) natural history are limited. We describe a large pediatric PSC cohort with longitudinal follow-up.

Methods: The present study records review of pediatric patients with PSC diagnosed between 1984 and 2014.

Results: N = 120 (63% M) ages 1 to 21 years (median 14 years) at diagnosis. 27% (31/113) had autoimmune sclerosing cholangitis (ASC), 24% had exclusive small duct PSC, METAVIR stage was F3-F4 in 41%. Eighty-one percent of patients with PSC had inflammatory bowel disease (IBD); most had ulcerative/indeterminate colitis (72/97), typically pancolitis (40/72). PSC-IBD was more common than ASC-IBD (85% vs 68%, P = 0.03). Median follow-up was 3.7 years (interquartile range [IQR] 1.5, 6.9). Median gamma glutamyl transferase decreased from baseline of 221 U/L (IQR 110, 425) to 104 U/L by 1 year postdiagnosis ([IQR 18,229], P < 0.0001), and then changed little. Mean fibrosis stage at diagnosis was 2.3 ± 1.4 (N = 91), and at 1 to 5 years was 2.6 ± 1.3 (N = 20). Transplant-free survival at 10 year was 89%; there were 6 liver transplants, 2 in patients with small duct PSC and 4 with diffuse large duct PSC. Although the cirrhosis rate was not significantly different in PSC with IBD versus without (22% vs 41%, P = 0.06), the former had a lower rate of liver transplantation (2% vs 18%, P = 0.01). The rate of cirrhosis was lower in patients diagnosed with IBD before PSC (15% vs 31%, P = 0.05).

Conclusions: In this largest reported pediatric PSC cohort, liver transplantation rate at 10 years was lower than that reported in adults. ASC and PSC had similar biochemical abnormalities and degree of fibrosis at diagnosis. PSC that developed after IBD diagnosis had a milder course, possibly reflecting earlier disease detection or milder phenotype.
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http://dx.doi.org/10.1097/MPG.0000000000001368DOI Listing
December 2016

Outcomes after discontinuation of routine use of transanastomotic biliary stents in pediatric liver transplantation at a single site.

Pediatr Transplant 2016 Aug 30;20(5):647-51. Epub 2016 May 30.

Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Routine use of transanastomotic biliary stents (RTBS) for biliary reconstruction in liver transplantation (LT) is controversial, with conflicting outcomes in adult randomized trials. Pediatric literature contains limited data. This study is a retrospective review of 99 patients who underwent first LT (2005-2014). In 2011, RTBS was discontinued at our center. This study describes biliary complications following LT with and without RTBS. 56 (56%) patients had RTBS. Median age at LT was 1.9 yr (IQR 0.7, 8.6); 55% were female. Most common indication for LT was biliary atresia (36%). Most common biliary reconstruction was Roux-en-Y choledochojejunostomy (75% with RTBS, 58% without RTBS, p = 0.09). Biliary complications (strictures, bile leaks, surgical revision) occurred in 23% without significant difference between groups (20% with RTBS, 28% without RTBS, p = 0.33). Patients with RTBS had routine cholangiography via the tube at 6-8 wk; thus, significantly more patients with RTBS had cholangiograms (91% vs. 19%, p < 0.0001). There was no difference in the number of patients who required therapeutic intervention via endoscopic or percutaneous transhepatic cholangiography (11% with RTBS, 19% no RTBS, p = 0.26). Routine use of RTBS for biliary reconstruction in pediatric LT may not be necessary, and possibly associated with need for costlier, invasive imaging without improvement in outcomes.
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http://dx.doi.org/10.1111/petr.12729DOI Listing
August 2016

Abnormal Liver Biochemistry Is Common in Pediatric Inflammatory Bowel Disease: Prevalence and Associations.

Inflamm Bowel Dis 2015 Dec;21(12):2848-56

*Division of Gastroenterology, Hepatology, and Nutrition, The University of Toronto, ON, Canada; †Department of Pediatrics, The University of Toronto, Toronto, ON, Canada; ‡Institute of Health Policy, Management and Evaluation, The University of Toronto, Toronto, ON, Canada; §Child Health Evaluative Sciences, Hospital for Sick Children and The University of Toronto, Toronto, ON, Canada; and ‖Division of Rheumatology, The University of Toronto, Toronto, ON, Canada.

Background: Liver enzymes (LEs) abnormalities associated with pediatric inflammatory bowel diseases (IBD) are understudied. We undertook to describe the development and associations of abnormal LEs in pediatric IBD.

Methods: We ascertained a cohort of 300 children with IBD and collected retrospective data. A Kaplan-Meier analysis determined the time to development of different thresholds of abnormal LEs. Associations between clinical variables and the development of abnormal LEs were determined.

Results: The probability of developing the first episode of abnormal LEs above the upper limit of normal (ULN) within 150 months was 58.1% (16.3% by 1 mo post-IBD diagnosis). There was a 6% prevalence of primary sclerosing cholangitis (PSC) or autoimmune sclerosing cholangitis (ASC) in this cohort. Of those diagnosed with PSC/ASC, 93% had persistent LE elevations at a threshold of >2× ULN, while those without PSC/ASC had a 4% probability of this abnormality. Elevated gamma glutamyltranspeptidase levels of 252 U/L had a 99% sensitivity and 71% specificity for PSC/ASC in IBD. After exclusion of patients with PSC/ASC, corticosteroids, antibiotics, and exclusive enteral nutrition demonstrated strongly positive associations with the first development of abnormal LEs >ULN (hazard ratio 2.1 [95% confidence interval, 1.3-3.3], hazard ratio 5.6 [95% confidence interval, 3.6-8.9], hazard ratio 4.2 [95% confidence interval, 1.6-11.3], respectively).

Conclusions: Abnormal LEs are common in pediatric IBD and occur early. PSC/ASC is associated with persistently high LEs and gamma glutamyltranspeptidase levels >252 U/L. Children with IBD are at risk of elevated LEs if they require medications other than 5-ASA to induce IBD remission.
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http://dx.doi.org/10.1097/MIB.0000000000000558DOI Listing
December 2015

The Academic Half-Day redesigned: Improving generalism, promoting CanMEDS and developing self-directed learners.

Paediatr Child Health 2015 Jan-Feb;20(1):30-4

Department of Pediatrics, McGill University, Montreal Children's Hospital, Montreal, Quebec; ; Centre for Medical Education, McGill University, Montreal, Quebec.

Background: The Montreal Children's Hospital Pediatric Residency Program redesigned its Academic Half-Day based on program concerns consistent with the published literature. These concerns included inadequate preparation for general paediatric practice, gaps in CanMEDS education and exclusive use of didactic lectures. Novel instructional methods included monthly simulation sessions to learn CanMEDS competencies, increased use of general paediatricians as instructors, implementation of a 'systems-based' curriculum and development of self-directed learning skills through activities such as 'Residents as Teachers'.

Method: A postimplementation online survey was sent to all 18 residents who had been exposed to both curricula. The survey was designed to determine the impact of the new curriculum on their perceived ability to retain information and acquire the competencies of a general paediatrician, and to assess the effect on their self-directed learning. Responses were recorded on a five-point Likert scale ranging from 'strongly disagree' to 'strongly agree'.

Results: Fourteen of 18 (78%) residents completed the survey. All residents preferred the 'systems-based' educational program. Seventy-nine percent of all residents agreed that the simulation sessions were an effective method of learning the CanMEDS competencies. Importantly, 64% of residents voluntarily read more about the topics presented and 71% agreed that they retained the content better. Moreover, 79% believed that changes made to the teaching curriculum better prepared them for a general paediatric practice and 64% of residents believed that it better 'supplements' learning in the clinical setting.

Conclusion: The authors propose that the new curriculum is comprehensive, while developing the skills required for life-long learning as a general paediatrician.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333752PMC
http://dx.doi.org/10.1093/pch/20.1.30DOI Listing
February 2015

Hepatotoxicity caused by methotrexate therapy in children with inflammatory bowel disease: a systematic review and meta-analysis.

Inflamm Bowel Dis 2014 Jan;20(1):47-59

1Division of Gastroenterology, Hepatology, and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; 2Neonatal Intensive Care Unit, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; 3Department of Clinical Epidemiology and Biostatistics, McMaster University, Toronto, ON, Canada; and 4Division of Rheumatology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Background: Methotrexate (MTX) is an immunomodulator used in pediatric inflammatory bowel disease (IBD) maintenance regimens. However, MTX use is associated with liver toxicity. We aimed to systematically review and meta-analyze the incidence of hepatotoxicity with MTX use among children with IBD.

Methods: We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases from 1946 to April 2013 for cohort studies and collected information about the study design, IBD treatment results, and hepatotoxicity. Pooled proportions of toxicity with 95% confidence interval (CI) were estimated using a random-effects model.

Results: Twelve high-quality studies were included in this review. Fifty-seven of 457 patients treated with MTX developed varied degrees of abnormal liver biochemistry. The pooled proportion of patients with abnormal liver biochemistry was 10.2% (95% CI 5.4%-18.5%) across all studies included in the meta-analysis. Due to hepatotoxicity, dose reductions were required in 6.4% (95% CI 4.3%-9.5%), whereas 4.5% (95% CI 2.8%-7.2%) of patients required discontinuation.

Conclusions: Hepatotoxicity after the use of MTX among IBD patients was a relatively common event. Monitoring for hepatotoxicity is strongly recommended, as discontinuation of MTX may be necessary in a significant proportion of children.
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http://dx.doi.org/10.1097/01.MIB.0000436953.88522.3eDOI Listing
January 2014

The role of diagnostic imaging and liver biopsy in the diagnosis of focal nodular hyperplasia in children.

Liver Int 2014 Feb 7;34(2):227-34. Epub 2013 Jul 7.

Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children (SickKids), Toronto, Ontario, Canada; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.

Background & Aims: Focal nodular hyperplasia (FNH), a benign liver tumour, has a characteristic appearance on diagnostic imaging (DI) and histology. The role of liver biopsy in children for the diagnosis of FNH is unclear. This study investigates the diagnostic accuracy of DI for FNH in children without comorbidities, compared to liver biopsy.

Methods: A total of 304 consecutive patients (age <18 years) with a biopsied liver mass were retrospectively ascertained (1990-2010). Individuals with a history of malignancy, liver disease or syndromes with increased malignancy risk were excluded. DI and biopsy data were reviewed.

Results: After excluding 205 cases, 99 liver masses were studied. Based on histology, the most common diagnosis was hepatoblastoma (46/99, 44%) followed by FNH (23/99, 23%). The mean age at FNH diagnosis was 11.1 ± 5.2 years, with female preponderance (78%), and a median follow-up of 1.35 years (interquartile range 0.54, 4.20 years). 19/23 biopsy-proven FNH met standard criteria for FNH on DI. In 4/23 cases of biopsy-proven FNH, imaging did not suggest FNH. Two false positive cases included adenoma and fibrolamellar hepatocellular carcinoma. On review of original reports, DI had 82.6% sensitivity and 97.4% specificity for the diagnosis of FNH. On blind review, the sensitivity of DI for FNH diagnosis was 81.3% for MRI (13/16), and 53.3% for CT (8/15).

Conclusions: In this cohort of children with liver masses and no comorbidities, a diagnosis of FNH by imaging was highly specific, and MRI was the most sensitive study for its diagnosis. Liver biopsy may be deferred in selected children if the DI, particularly MRI, is indicative of FNH.
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http://dx.doi.org/10.1111/liv.12241DOI Listing
February 2014

Variation in care for children with esophageal varices: a study of physicians', patients', and families' approaches and attitudes.

J Pediatr Gastroenterol Nutr 2011 Jun;52(6):751-5

Division of Paediatrics, Gastroenterology, Hepatology & Nutrition Unit, Pontificia Universidad Católica de Chile, Santiago, Chile.

Background And Aims: Inadequate evidence to guide the management of children with esophageal varices may lead to variation in care and the provision of poor-quality care to some children. The aims of the study were to describe approaches taken by pediatric gastroenterologists for the management of esophageal varices in children, and to determine the attitudes of children, parents, and physicians toward screening endoscopy for identification of varices.

Methods: Canadian pediatric gastroenterologists and hepatologists were questioned about their approaches to screening for esophageal varices and therapy to prevent or treat variceal hemorrhage. Consecutive children with portal hypertension and their parents were surveyed about attitudes to screening endoscopy.

Results: Forty-seven of 72 (65%) physicians responded. Seventy percent of respondents screen for esophageal varices in selected children, most using endoscopy (77%). Fifty-eight percent of respondents who screen for varices would provide primary prophylactic treatment. Most would treat an acute variceal bleed with antibiotics, acid suppression, octreotide, and endoscopy within 24 hours (76%) and then secondary prophylaxis with endoscopic variceal ligation (96%) or β-blockers (28%). Among 29 families surveyed, 63% of parents and 50% of patients would agree to screening endoscopy to understand their risk of variceal bleeding and 67% if prophylactic therapy were available. Families were more concerned about the risk of endoscopic adverse events than were gastroenterologists.

Conclusions: Pediatric gastroenterologists vary in the care they provide for children at risk for esophageal varices and their attitudes toward the role of screening endoscopy differ from that of their patients. Further evidence is required to support practice guidelines that may reduce variation in care and thus improve its quality.
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http://dx.doi.org/10.1097/MPG.0b013e318213be81DOI Listing
June 2011
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