Publications by authors named "Shikha S Sundaram"

51 Publications

Predictors of survival following liver transplantation for pediatric hepatoblastoma and hepatocellular carcinoma: Experience from the Society of Pediatric Liver Transplantation (SPLIT).

Am J Transplant 2022 Jan 6. Epub 2022 Jan 6.

Children's Hospital Colorado and University of Colorado, Pediatrics, Aurora, CO.

Management of unresectable pediatric hepatoblastoma (HB) and hepatocellular carcinoma (HCC) remains challenging. The Society of Pediatric Liver Transplantation (SPLIT) database was used to study survival predictors in pediatric liver transplantation (LT) for HB and HCC. Event-free survival (EFS), associated risk factors, and post-operative complications were studied in children requiring LT for HB/HCC at 16 SPLIT centers. Three-year EFS was 81% for HB (n=157) and 62% for HCC (n=18) transplants. Of HB transplants, 6.9% were PRETEXT II and 15.3% were POST-TEXT I/II. Tumor extent did not impact survival (p=NS). Salvage (n=13) and primary HB transplants had similar 3-year EFS (62% versus 78%, p=NS). Among HCC transplants, 3-year EFS was poorer in older patients (38% in ≥8-year-olds vs 86% <8-year-olds), larger tumors (48% for those beyond versus 83% within Milan criteria, p=NS). Risk of infection (HR 1.5, 95%CI 1.1-2.2, p=0.02) and renal injury (HR 2.4, 95%CI 1.7-3.3, p<0.001) were higher in malignant versus non-malignant LT. Survival is favorable for pediatric HB and HCC LT, including outcomes after salvage transplant. Unexpected numbers of LTs occurred in PRE/POST-TEXT I/II tumors. Judicious patient selection is critical to distinguish tumors that are potentially resectable; simultaneously, we must advocate for patients with unresectable malignancies to receive organs.
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http://dx.doi.org/10.1111/ajt.16945DOI Listing
January 2022

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

Extracorporeal membrane oxygenation as rescue therapy in a pediatric liver transplant recipient with very severe hepatopulmonary syndrome.

Pediatr Transplant 2021 Nov 6:e14185. Epub 2021 Nov 6.

Colorado Center for Transplantation Care, Research and Education, Division of Transplant Surgery, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.

Background: In children with cirrhosis, the prevalence of HPS ranges from 3% to 20%, resulting in impaired gas exchange due to alterations in pulmonary microvasculature. LT is the gold-standard cure for cirrhosis complicated by HPS and should ideally be performed prior to the development of severe HPS due to increased risk for post-transplant hypoxia, right heart failure, and outflow obstruction.

Methods: We present a case of a 13-year-old man, who underwent pediatric LT for severe HPS complicated by postoperative respiratory collapse, requiring a 92-day course of veno-venous ECMO.

Results: Post-transplant, despite BiPAP, inhaled nitric oxide and isoproterenol infusion, he remained hypoxic postoperatively and acutely decompensated on postoperative day 25, requiring veno-venous ECMO. After 84 days on ECMO, a persistent large splenorenal shunt was identified that was embolized by interventional radiology, and 8 days after shunt embolization and ASD closure, he was successfully weaned off ECMO.

Conclusions: This case describes the longest known duration of ECMO in a pediatric LT recipient and a unique improvement in hypoxemia following a portosystemic shunt closure. ECMO presents a heroic rescue measure for pediatric LT recipients with HPS that develops acute respiratory failure postoperatively refractory to alternative measures.
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http://dx.doi.org/10.1111/petr.14185DOI Listing
November 2021

Neonatal Presentation of Congenital Portosystemic Shunt.

J Pediatr 2021 Oct 21. Epub 2021 Oct 21.

Department of Radiology, University of Colorado Hospital; Section of Radiology, Children's Hospital Colorado, Aurora, Colorado.

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http://dx.doi.org/10.1016/j.jpeds.2021.10.010DOI Listing
October 2021

Malnutrition in Biliary Atresia: Assessment, Management, and Outcomes.

Liver Transpl 2021 Oct 20. Epub 2021 Oct 20.

Department of Pediatrics, Pediatric Liver Center, Digestive Health Institute and Section of Pediatric Gastroenterology, Hepatology & Nutrition, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA.

Children with biliary atresia (BA), particularly infants, are at high risk for malnutrition attributed to a multitude of factors, including poor oral intake and intolerance of enteral feeding, fat malabsorption, abnormal nutrient metabolism, and increased caloric demand. Malnutrition and sarcopenia negatively impact outcomes in BA, leading to higher pretransplant and posttransplant morbidity and mortality. This review summarizes factors contributing to nutritional deficiencies in BA and offers an organized approach to the assessment and management of malnutrition in this vulnerable population.
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http://dx.doi.org/10.1002/lt.26339DOI Listing
October 2021

Decreased access to pediatric liver transplantation during the COVID-19 pandemic.

Pediatr Transplant 2021 Oct 11:e14162. Epub 2021 Oct 11.

Section of Gastroenterology, Hepatology, and Nutrition, Digestive Health Institute, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.

Background: The COVID-19 pandemic has affected all aspects of the US healthcare system, including liver transplantation. The objective of this study was to understand national changes to pediatric liver transplantation during COVID-19.

Methods: Using SRTR data, we compared waitlist additions, removals, and liver transplantations for pre-COVID-19 (March-November 2016-2019), early COVID-19 (March-May 2020), and late COVID-19 (June-November 2020).

Results: Waitlist additions decreased by 25% during early COVID-19 (41.3/month vs. 55.4/month, p < .001) with black candidates most affected (p = .04). Children spent longer on the waitlist during early COVID-19 compared to pre-COVID-19 (140 vs. 96 days, p < .001). There was a 38% decrease in liver transplantations during early COVID-19 (IRR 0.62, 95% CI 0.49-0.78), recovering to pre-pandemic rates during late COVID-19 (IRR 1.03, NS), and no change in percentage of living and deceased donors. White children had a 30% decrease in overall liver transplantation but no change in living donor liver transplantation (IRR 0.7, 95% CI 0.50-0.95; IRR 0.96, NS), while non-white children had a 44% decrease in overall liver transplantation (IRR 0.56, 95% CI 0.40-0.77) and 81% decrease in living donor liver transplantation (IRR 0.19, 95% CI 0.02-0.76).

Conclusions: The COVID-19 pandemic decreased access to pediatric liver transplantation, particularly in its early stage. There were no regional differences in liver transplantation during COVID-19 despite the increased national sharing of organs. While pediatric liver transplantation has resumed pre-pandemic levels, ongoing racial disparities must be addressed.
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http://dx.doi.org/10.1111/petr.14162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8646490PMC
October 2021

Hepatic Fat in Early Childhood Is Independently Associated With Estimated Insulin Resistance: The Healthy Start Study.

J Clin Endocrinol Metab 2021 10;106(11):3140-3150

Department of Pediatrics, University of Colorado School of Medicine, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA.

Background: Fatty liver disease is a common metabolic abnormality in adolescents with obesity but remains understudied in early childhood.

Objectives: To describe hepatic fat deposition in prepubertal children and examine cross-sectional associations with metabolic markers and body composition.

Methods: Data were from 286 children ages 4 to 8 years old in the Healthy Start Study, a longitudinal prebirth cohort in Colorado (USA). Assessments included magnetic resonance imaging to quantify hepatic and abdominal fats, fasting blood draws to measure metabolic markers, and air displacement plethysmography to measure body composition (fat mass and fat-free mass).

Results: The median (interquartile range) for hepatic fat was 1.65% (1.24%, 2.11%). Log-transformed hepatic fat was higher in Hispanic [mean (95% CI): 0.63 (0.52, 0.74)] vs non-Hispanic white children [0.46 (0.38, 0.53), P = 0.01] and children with overweight/obesity [0.64 (0.49, 0.79)] vs normal-weight [0.47 (0.40, 0.53), P = 0.02]. Higher log-hepatic fat was associated with higher insulin [β (95% CI): 1.47 (0.61, 2.33) uIU/mL, P = 0.001] and estimated insulin resistance (homeostatic model assessment) [0.40 (0.20, 0.60), P < 0.001] in the full sample and glucose [5.53 (2.84, 8.21) mg/dL, P < 0.001] and triglycerides [10.92 (2.92,18.91) mg/dL, P = 0.008] in boys, in linear regression models adjusted for sociodemographics, maternal/perinatal confounders, and percentage body fat. Log-hepatic fat was also associated with abdominal subcutaneous adipose tissue [SAT; 7.37 (1.12,13.60) mm2, P = 0.02] in unadjusted models, but this was attenuated and insignificant after adjusting for confounders.

Conclusions: While hepatic fat was low in children 4 to 8 years old, it was independently associated with estimated insulin resistance and exhibited sex-specific associations with glucose and triglycerides, suggesting hepatic fat may be an early indicator of metabolic dysfunction in youth.
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http://dx.doi.org/10.1210/clinem/dgab541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530740PMC
October 2021

Challenging the Traditional Paradigm of Supply and Demand in Pediatric Liver Transplantation Through Nondirected Living Donation: A Case Series.

Liver Transpl 2021 10 31;27(10):1392-1400. Epub 2021 Jul 31.

Division of Transplantation, Department of Surgery, University of Colorado School of Medicine, Aurora, CO.

A gap exists between the demand for pediatric liver transplantation and the supply of appropriate size-matched donors. We describe our center's experience with pediatric liver transplantation using anonymous nondirected living liver donors (ND-LLD). First-time pediatric liver transplant candidates listed at our center between January 2012 and June 2020 were retrospectively reviewed and categorized by donor graft type, and recipients of ND-LLD grafts were described. A total of 13 ND-LLD pediatric liver transplantations were performed, including 8 left lateral segments, 4 left lobes, and 1 right lobe. Of the ND-LLD recipients, 5 had no directed living donor evaluated, whereas the remaining 8 (62%) had all potential directed donors ruled out during the evaluation process. Recipient and graft survival were 100% during a median follow-up time of 445 (range, 70-986) days. Of ND-LLDs, 69% were previous living kidney donors, and 1 ND-LLD went on to donate a kidney after liver donation. Of the ND-LLDs, 46% were approved prior to the recipient being listed. Over time, the proportion of living donor transplants performed, specifically from ND-LLDs, increased, and the number of children on the waiting list decreased. The introduction of ND-LLDs to a pediatric liver transplant program can expand the benefit of living donor liver transplantation to children without a suitable directed living donor while achieving excellent outcomes for both the recipients and donors.
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http://dx.doi.org/10.1002/lt.26108DOI Listing
October 2021

Higher Mortality in Pediatric Liver Transplant Candidates With Sarcopenia.

Liver Transpl 2021 06;27(6):808-817

Pediatric Gastroenterology, Hepatology & Nutrition and the Digestive Health Institute, Children's Hospital Colorado, University of Colorado, Aurora, CO.

Little is known about the impact of sarcopenia (reduced muscle mass and function) in pediatric chronic liver disease. We compared psoas muscle surface area (PMSA), measured at the 4th lumbar vertebrae, in children listed for liver transplantation (LT) to that of healthy controls and studied the impact of sarcopenia on transplant-associated outcomes. The effect of PMSA (raw value and z score) on survival was studied using multivariable proportional hazards, whereas the impact of PMSA on other transplant-associated outcomes was assessed by multivariable linear or logistic regression. The correlation of PMSA with anthropometric values and markers of disease severity was studied using Spearman's rank-order correlation. Mean PMSA was significantly lower in LT candidates (n = 57, 699.4 ± 591.9 mm [mean ± SD]) than controls (n = 53, 1052.9 ± 960.7 mm ; P = 0.02). For LT candidates, there was an increased risk of death (either while on the waiting list or following transplantation) with lower PMSA (hazard ratio [HR], 1.6 per 100 mm [P = 0.03]; 95% confidence interval [CI], 1.1-2.8), amounting to a 4.9 times higher risk of death for every 1 unit decrease in PMSA z score (HR, 4.9 [P = 0.05], 95% CI, 1.2-34.5), adjusting for age and sex. PMSA did not correlate with posttransplant length of intubation, hospital length of stay, or perioperative complications. PMSA also did not correlate with calculated (r = 0.10, P = 0.60) or appealed Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores (r = 0.10, P = 0.69). Pediatric LT candidates have a significant reduction in muscle compared with controls. LT candidates with lower PMSA experience significant increases in mortality. As such, sarcopenia may provide a novel indicator of disease severity in children with chronic liver disease.
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http://dx.doi.org/10.1002/lt.26027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187298PMC
June 2021

Successful non-directed living liver donor transplant for an infant with biliary atresia during the COVID-19 pandemic.

Pediatr Transplant 2020 12 14;24(8):e13816. Epub 2020 Aug 14.

Section of Gastroenterology, Hepatology and Nutrition and the Digestive Health Institute, University of Colorado School of Medicine, Anschutz Medical Campus & Children's Hospital Colorado, Aurora, Colorado, USA.

Amidst the coronavirus (COVID-19) pandemic, the American Society for Transplant Surgeons has recommended that only urgent liver transplant with deceased donors should occur. However, young pediatric candidates rely on living donors for lifesaving transplant. We present a case of non-directed left lateral lobe living liver donor transplant for a 7-month-old child with biliary atresia experiencing repeated life-threatening episodes of sepsis and cholangitis from infected bile lakes. Using careful preoperative planning among the entire multidisciplinary team, paying meticulous attention to infection control pre- and post-operatively, and taking advantage of robust telehealth technology both in and out of the hospital, a successful transplant was achieved. Amidst the COVID pandemic, non-directed liver transplantation can be safely achieved for pediatric recipients.
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http://dx.doi.org/10.1111/petr.13816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988506PMC
December 2020

Improvements in Disease-Specific Health-Related Quality of Life of Pediatric Liver Transplant Recipients During Immunosuppression Withdrawal.

Liver Transpl 2021 05;27(5):735-746

Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chicago, IL.

Long-term immunosuppression (IS) leads to systemic complications affecting health-related quality of life (HRQOL) in pediatric liver transplantation (LT) recipients. We serially assessed HRQOL using the PedsQL Generic and Multidimensional Fatigue Scales and Family Impact and Transplant Modules as part of a multicenter prospective immunosuppression withdrawal (ISW) trial between 2012 and 2018. Participants received a primary LT ≥4 years before the study and were on stable IS with normal liver tests and without rejection in the prior 2 years. IS was withdrawn in 7 steps over 36 to 48 weeks. HRQOL was assessed at regular intervals. The primary endpoint was change in disease-specific HRQOL measured by the PedsQL Transplant Module. Generic HRQOL was measured by the PedsQL Generic Scale and was compared with an age-matched and sex-matched multicenter cohort. Of the 88 participants, 39 were boys, median age was 11 years (range, 8-13), and time since transplant was 9 years (range, 6-11). For 36 months, disease-specific HRQOL improved for all participants, whereas generic HRQOL was unchanged. Neither generic nor disease-specific HRQOL changed for the 35 participants who developed acute rejection during ISW. In the first use of patient-reported outcome measures during an ISW trial, we found improvements in disease-specific HRQOL in all participants and no lasting detrimental effects in those who experienced rejection.
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http://dx.doi.org/10.1002/lt.25963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185886PMC
May 2021

Nonfasted Liver Stiffness Correlates with Liver Disease Parameters and Portal Hypertension in Pediatric Cholestatic Liver Disease.

Hepatol Commun 2020 Nov 5;4(11):1694-1707. Epub 2020 Aug 5.

University of Michigan Ann Arbor MI USA.

Elastographic measurement of liver stiffness is of growing importance in the assessment of liver disease. Pediatric experiences with this technique are primarily single center and limited in scope. The Childhood Liver Disease Research Network provided a unique opportunity to assess elastography in a well-characterized multi-institutional cohort. Children with biliary atresia (BA), alpha-1 antitrypsin deficiency (A1ATD), or Alagille syndrome (ALGS) followed in a prospective longitudinal network study were eligible for enrollment in a prospective investigation of transient elastography (FibroScan). Studies were performed in participants who were nonfasted and nonsedated. Liver stiffness measurements (LSMs) were correlated with standard clinical and biochemical parameters of liver disease along with a research definition of clinically evident portal hypertension (CEPH) graded as absent, possible, or definite. Between November 2016 and August 2019, 550 participants with a mean age of 8.8 years were enrolled, 458 of whom had valid LSMs (BA, n = 254; A1ATD, n = 104; ALGS, n = 100). Invalid scans were more common in participants <2 years old. There was a positive correlation between LSM and total bilirubin, international normalized ratio (INR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), GGT to platelet ratio (GPR), pediatric end-stage liver disease score, AST to platelet ratio index, and spleen size, and a negative correlation with albumin and platelet count in BA, with similar correlations for A1ATD (except AST, ALT, and albumin) and ALGS (except for INR, GGT, GPR, and ALT). Possible or definite CEPH was more common in BA compared to ALGS and A1ATD. LSM was greater in definite versus absent CEPH in all three diseases. Disease-specific clinical and biochemical characteristics of the different CEPH grades were observed. : It is feasible to obtain LSMs in children, especially over the age of 2 years. LSM correlates with liver parameters and portal hypertension, although disease-specific patterns exist.
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http://dx.doi.org/10.1002/hep4.1574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603532PMC
November 2020

A community divided: Post-transplant live vaccine practices among Society of Pediatric Liver Transplantation (SPLIT) centers.

Pediatr Transplant 2020 11 26;24(7):e13804. Epub 2020 Aug 26.

Section of Gastroenterology, Hepatology and Nutrition, Digestive Health Institute, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA.

Background: Historically, the IDSA and the AST have recommended that live vaccines not be administered post-transplant due to concern for induction of vaccine-strain disease in immunocompromised hosts. However, recent prospective studies and revised AST guidelines published in April 2019 suggest that in the current era of immunosuppression minimization, live vaccines may be safely administered to select transplant recipients with resulting immunoprotection. The goal of this study was to assess current post-transplant live vaccine practices at individual pediatric liver transplant centers following the updated AST guidelines.

Methods: A six-item email survey detailing center-specific post-transplant live vaccine practices followed by up to three response-specific questions were distributed between July 2019 and May 2020 to a representative from each center participating in the SPLIT consortium.

Results: The overall survey response rate was 93% (41/44 centers). Only 29% (12/41) of centers offer live vaccines post-transplant; each of these 12 centers uses different eligibility criteria for live vaccines. There was no difference between large (ten or more transplants per year) and small (less than ten transplants per year) centers in likelihood to offer live vaccines post-transplant. The main reasons for a center not offering post-transplant live vaccines were safety concerns and inability to reach group consensus.

Conclusions: The majority of pediatric liver transplant centers are reluctant to offer live vaccines post-transplant despite the updated AST guidelines. Prospective multicenter studies are needed to confirm safety and immunogenicity of live vaccines post-transplant.
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http://dx.doi.org/10.1111/petr.13804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112257PMC
November 2020

Hepatitis C in 2020: A North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper.

J Pediatr Gastroenterol Nutr 2020 09;71(3):407-417

Children's Hospital of Colorado, Digestive Health Institute, University of Colorado School of Medicine, Aurora, CO.

In 1989, a collaboration between the Centers for Disease Control (CDC) and a California biotechnology company identified the hepatitis C virus (HCV, formerly known as non-A, non-B hepatitis virus) as the causative agent in the epidemic of silent posttransfusion hepatitis resulting in cirrhosis. We now know that, the HCV genome is a 9.6 kb positive, single-stranded RNA. A single open reading frame encodes a 3011 amino acid residue polyprotein that undergoes proteolysis to yield 10 individual gene products, consisting of 3 structural proteins (core and envelope glycoproteins E1 and E2) and 7 nonstructural (NS) proteins (p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B), which participate in posttranslational proteolytic processing and replication of HCV genetic material. Less than 25 years later, a new class of medications, known as direct-acting antivirals (DAAs) which target these proteins, were introduced to treat HCV infection. These highly effective antiviral agents are now approved for use in children as young as 3 years of age and have demonstrated sustained virologic responses exceeding 90% in most genotypes. Although tremendous scientific progress has been made, the incidence of acute HCV infections has increased by 4-fold since 2005, compounded in the last decade by a surge in opioid and intravenous drug use. Unfortunately, awareness of this deadly hepatotropic virus among members of the lay public remains limited. Patient education, advocacy, and counseling must, therefore, complement the availability of curative treatments against HCV infection if this virus is to be eradicated.
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http://dx.doi.org/10.1097/MPG.0000000000002814DOI Listing
September 2020

Efficacy and Safety of Immunosuppression Withdrawal in Pediatric Liver Transplant Recipients: Moving Toward Personalized Management.

Hepatology 2021 05;73(5):1985-2004

Department of Pathology, University of Pittsburgh, Pittsburgh, PA.

Background And Aims: Tolerance is transplantation's holy grail, as it denotes allograft health without immunosuppression and its toxicities. Our aim was to determine, among stable long-term pediatric liver transplant recipients, the efficacy and safety of immunosuppression withdrawal to identify operational tolerance.

Approach And Results: We conducted a multicenter, single-arm trial of immunosuppression withdrawal over 36-48 weeks. Liver tests were monitored biweekly (year 1), monthly (year 2), and bimonthly (years 3-4). For-cause biopsies were done at investigators' discretion but mandated when alanine aminotransferase or gamma glutamyltransferase exceeded 100 U/L. All subjects underwent final liver biopsy at trial end. The primary efficacy endpoint was operational tolerance, defined by strict biochemical and histological criteria 1 year after stopping immunosuppression. Among 88 subjects (median age 11 years; 39 boys; 57 deceased donor grafts), 33 (37.5%; 95% confidence interval [CI] 27.4%, 48.5%) were operationally tolerant, 16 were nontolerant by histology (met biochemical but failed histological criteria), and 39 were nontolerant by rejection. Rejection, predicted by subtle liver inflammation in trial entry biopsies, typically (n = 32) occurred at ≤32% of the trial-entry immunosuppression dose and was treated with corticosteroids (n = 32) and/or tacrolimus (n = 38) with resolution (liver tests within 1.5 times the baseline) for all but 1 subject. No death, graft loss, or chronic, severe, or refractory rejection occurred. Neither fibrosis stage nor the expression level of a rejection gene set increased over 4 years for either tolerant or nontolerant subjects.

Conclusions: Immunosuppression withdrawal showed that 37.5% of selected pediatric liver-transplant recipients were operationally tolerant. Allograft histology did not deteriorate for either tolerant or nontolerant subjects. The timing and reversibility of failed withdrawal justifies future trials exploring the efficacy, safety, and potential benefits of immunosuppression minimization.
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http://dx.doi.org/10.1002/hep.31520DOI Listing
May 2021

The effect of sleep on gastrointestinal functioning in common digestive diseases.

Lancet Gastroenterol Hepatol 2020 06;5(6):616-624

Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address:

Sleep quality and sleep disorders affect symptom manifestation and the pathogenesis of digestive diseases. Sleep is largely regulated by the light-dark cycle and associated circadian rhythms. These occurrences are closely regulated through several mechanisms with direct effects on the gastrointestinal tract. Misalignment of the circadian system is a common cause of sleep complaints, which play an important role in the presentation of many gastrointestinal disorders. This Review will focus on sleep disorders and how these alterations in sleep play an important role in many commonly encountered digestive diseases, such as gastro-oesophageal reflux disease, irritable bowel syndrome, inflammatory bowel disease, and non-alcoholic fatty liver disease. Therapeutic interventions focusing on resolving sleep disorders could optimise treatment and improve quality of life in these patients.
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http://dx.doi.org/10.1016/S2468-1253(19)30412-1DOI Listing
June 2020

Liver Diseases in the Perinatal Period: Interactions Between Mother and Infant.

Hepatology 2020 04 18;71(4):1474-1485. Epub 2020 Mar 18.

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO.

Liver diseases affecting the mother and infant dyad may present in the perinatal period from 20 weeks of gestation to 28 days of life. This review will focus on the current approach to neonatal acute liver failure and the progress made in the diagnosis and management of gestational alloimmune liver disease. It will highlight mother-to-child transmission of viral hepatitis, both management and public health implications. Emerging concepts implicating maternal obesity and nutrition in the development of a rapidly progressive nonalcoholic steatohepatitis phenotype in the offspring will be discussed. Finally, the presentation and management of acute fatty liver of pregnancy and intrahepatic cholestasis of pregnancy, and their impact on the fetus, will be reviewed.
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http://dx.doi.org/10.1002/hep.31109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150638PMC
April 2020

Immunization Status at the Time of Liver Transplant in Children and Adolescents.

JAMA 2019 11;322(18):1822-1824

Adult and Child Consortium for Health Outcomes Research and Delivery Science (ACCORDS), University of Colorado, Denver, Aurora.

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http://dx.doi.org/10.1001/jama.2019.14386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865293PMC
November 2019

A Prospective Trial of Withdrawal and Reinstitution of Ursodeoxycholic Acid in Pediatric Primary Sclerosing Cholangitis.

Hepatol Commun 2019 Nov 29;3(11):1482-1495. Epub 2019 Aug 29.

Pediatrics Baylor College of Medicine Houston TX.

Ursodeoxycholic acid (UDCA) is commonly used to treat several liver disorders in adults and children, including primary sclerosing cholangitis (PSC) for which it is not U.S. Food and Drug Administration approved. UDCA treatment has an uncertain impact on disease outcomes and has been reported in high doses to be associated with worse outcome in adults with PSC. In this context, controlled withdrawal and reintroduction of UDCA in children with PSC were studied. Prior to study initiation, participants were required to have alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) <2 times the upper limit of normal on stable UDCA dosing. The study included four phases: I (stable dosing), II (50% UDCA reduction), III (UDCA discontinuation), IV (UDCA reintroduction), with a primary endpoint of change in ALT and GGT between phases I and III. We enrolled 27 participants (22 completed) between March 2011 and June 2016. Changes in mean ALT and GGT between phases I and III were ALT, +29.5 IU/L ( = 0.105) and GGT, +60.4 IU/L ( = 0.003). In 7 participants, ALT and GGT ≤29 IU/L did not rise above 29 IU/L (null response group). Eight participants had increases of ALT or GGT >100 IU/L (flare group). None developed elevated bilirubin. All flares responded to UDCA reinstitution. Serum GGT, interleukin-8, and tumor necrosis factor α levels were higher in the flare group at baseline. Liver biochemistries increased in children with PSC during controlled UDCA withdrawal; one third increased above 100 IU/L and one third remained normal during UDCA withdrawal. : The impact of prolonged UDCA use in childhood PSC and the significance of a biochemical flare are unclear. Further studies of the natural history and treatment of pediatric PSC and UDCA use are needed.
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http://dx.doi.org/10.1002/hep4.1421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824074PMC
November 2019

Health-Related Quality of Life and Cognitive Functioning in Pediatric Liver Transplant Recipients.

Liver Transpl 2020 01 6;26(1):45-56. Epub 2019 Nov 6.

Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.

The goal of this work was to examine the change in health-related quality of life (HRQOL) and cognitive functioning from early childhood to adolescence in pediatric liver transplantation (LT) recipients. Patients were recruited from 8 North American centers through the Studies of Pediatric Liver Transplantation consortium. A total of 79 participants, ages 11-18 years, previously tested at age 5-6 years in the Functional Outcomes Group study were identified as surviving most recent LT by 2 years and in stable medical follow-up. The Pediatric Quality of Life 4.0 Generic Core Scale, Pediatric Quality of Life Cognitive Function Scale, and PROMIS Pediatric Cognitive Function tool were distributed to families electronically. Data were analyzed using repeated measures and paired t tests. Predictive variables were analyzed using univariate regression analysis. Of the 69 families contacted, 65 (94.2%) parents and 61 (88.4%) children completed surveys. Median age of participants was 16.1 years (range, 12.9-18.0 years), 55.4% were female, 33.8% were nonwhite, and 84.0% of primary caregivers had received at least some college education. Median age at LT was 1.1 years (range, 0.1-4.8 years). The majority of participants (86.2%) were not hospitalized in the last year. According to parents, adolescents had worse HRQOL and cognitive functioning compared with healthy children in all domains. Adolescents reported HRQOL similar to healthy children in all domains except psychosocial, school, and cognitive functioning (P = 0.02; P < 0.001; P = 0.04). Participants showed no improvement in HRQOL or cognitive functioning over time. For cognitive and school functioning, 60.0% and 50.8% of parents reported "poor" functioning, respectively (>1 standard deviation below the healthy mean). Deficits in HRQOL seem to persist in adolescence. Over half of adolescent LT recipients appear to be at risk for poor school and cognitive functioning, likely reflecting attention and executive function deficits.
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http://dx.doi.org/10.1002/lt.25634DOI Listing
January 2020

Barriers to ideal outcomes after pediatric liver transplantation.

Pediatr Transplant 2019 09 25;23(6):e13537. Epub 2019 Jul 25.

Mount Sinai Kravis Childrens Hospital and Recanati/Miller Transplant Institute, New York City, New York.

Long-term survival for children who undergo LT is now the rule rather than the exception. However, a focus on the outcome of patient or graft survival rates alone provides an incomplete and limited view of life for patients who undergo LT as an infant, child, or teen. The paradigm has now appropriately shifted to opportunities focused on our overarching goals of "surviving and thriving" with long-term allograft health, freedom of complications from long-term immunosuppression, self-reported well-being, and global functional health. Experts within the liver transplant community highlight clinical gaps and potential barriers at each of the pretransplant, intra-operative, early-, medium-, and long-term post-transplant stages toward these broader mandates. Strategies including clinical research, innovation, and quality improvement targeting both traditional as well as PRO are outlined and, if successfully leveraged and conducted, would improve outcomes for recipients of pediatric LT.
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http://dx.doi.org/10.1111/petr.13537DOI Listing
September 2019

Nocturnal Hypoxia Activation of the Hedgehog Signaling Pathway Affects Pediatric Nonalcoholic Fatty Liver Disease Severity.

Hepatol Commun 2019 Jul 17;3(7):883-893. Epub 2019 Apr 17.

Duke University Durham NC.

Chronic intermittent hypoxia and hedgehog (Hh) pathway dysregulation are associated with nonalcoholic fatty liver disease (NAFLD) progression. In this study, we determined the relationship between obstructive sleep apnea (OSA)/nocturnal hypoxia and Hh signaling in pediatric NAFLD. Adolescents with histologic NAFLD (n = 31) underwent polysomnogram testing, laboratory testing, and Sonic Hh (SHh), Indian hedgehog (IHh), glioblastoma-associated oncogene 2 (Gli2), keratin 7 (K7), α-smooth muscle actin (α-SMA), and hypoxia-inducible factor 1α (HIF-1α) immunohistochemistry. Aspartate aminotransferase (AST) correlated with SHh,  = 0.64; Gli2,  = 0.4; α-SMA,  = 0.55; and K7,  = 0.45 ( < 0.01), as did alanine aminotransferase (ALT) (SHh,  = 0.51; Gli2,  = 0.43; α-SMA,  = 0.51;  < 0.02). SHh correlated with NAFLD activity score ( = 0.39), whereas IHh correlated with inflammation ( = -0.478) and histologic grade ( = -0.43);  < 0.03. Subjects with OSA/hypoxia had higher SHh (4.0 ± 2.9 versus 2.0 ± 1.5), Gli2 (74.2 ± 28.0 versus 55.8 ± 11.8), and α-SMA (6.2 ± 3.3 versus 4.3 ± 1.2); compared to those without ( < 0.03). OSA severity correlated with SHh ( = 0.31;  = 0.09) and Gli2 ( = 0.37;  = 0.04) as did hypoxia severity, which was associated with increasing SHh ( = -0.53), Gli2 ( = -0.52), α-SMA ( = -0.61), and K7 ( = -0.42);  < 0.02. Prolonged O desaturations <90% also correlated with SHh ( = 0.55) and Gli2 ( = 0.61);  < 0.05. : The Hh pathway is activated in pediatric patients with NAFLD with nocturnal hypoxia and relates to disease severity. Tissue hypoxia may allow for functional activation of HIF-1α, with induction of genes important in epithelial-mesenchymal transition, including SHh, and NAFLD progression.
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http://dx.doi.org/10.1002/hep4.1354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601320PMC
July 2019

Clinical Practice Approach to Nonalcoholic Fatty Liver Disease by Pediatric Gastroenterologists in the United States.

J Pediatr Gastroenterol Nutr 2019 02;68(2):182-189

Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla.

Objectives: Nonalcoholic fatty liver disease (NAFLD) is common; however, no information is available on how pediatric gastroenterologists in the United States manage NAFLD. Therefore, study objectives were to understand how pediatric gastroenterologists in the US approach the management of NAFLD, and to identify barriers to care for children with NAFLD.

Methods: We performed structured one-on-one interviews to ascertain each individual pediatric gastroenterologist's approach to the management of NAFLD in children. Responses were recorded from open-ended questions regarding screening for comorbidities, recommendations regarding nutrition, physical activity, medications, and perceived barriers to care.

Results: Response rate was 72.0% (486/675). Mean number of patients examined per week was 3 (standard deviation [SD] 3.5). Dietary intervention was recommended by 98.4% of pediatric gastroenterologists. Notably, 18 different dietary recommendations were reported. A majority of physicians provided targets for exercise frequency (72.6%, mean 5.6 days/wk, SD 1.6) and duration (69.9%, mean 40.2 minutes/session, SD 16.4). Medications were prescribed by 50.6%. Almost one-half of physicians (47.5%) screened for type 2 diabetes, dyslipidemia, and hypertension. Providers who spent more than 25 minutes at the initial visit were more likely to screen for comorbidities (P = 0.003). Barriers to care were reported by 92.8% with 29.0% reporting ≥3 barriers.

Conclusions: The majority of US pediatric gastroenterologists regularly encounter children with NAFLD. Varied recommendations regarding diet and exercise highlight the need for prospective clinical trials. NAFLD requires a multidimensional approach with adequate resources in the home, community, and clinical setting.
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http://dx.doi.org/10.1097/MPG.0000000000002194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053385PMC
February 2019

Treating Obstructive Sleep Apnea and Chronic Intermittent Hypoxia Improves the Severity of Nonalcoholic Fatty Liver Disease in Children.

J Pediatr 2018 07 8;198:67-75.e1. Epub 2018 May 8.

Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, CO.

Objective: To determine the effects of treating obstructive sleep apnea/nocturnal hypoxia on pediatric nonalcoholic fatty liver disease (NAFLD) severity and oxidative stress.

Study Design: Biopsy proven participants (n = 9) with NAFLD and obstructive sleep apnea/hypoxia were studied before and after treatment with continuous positive airway pressure (CPAP) for sleep disordered breathing, including laboratory testing and markers of oxidative stress, urine F(2)-isoprostanes.

Results: Adolescents (age 11.5 ± 1.2 years; body mass index, 29.5 ± 3.8 kg/m) with significant NAFLD (mean histologic necroinflammation grade, 2.3 ± 0.9; fibrosis stage, 1.4 ± 1.3; NAFLD Activity Score summary, 4.8 ± 1.6) had obstructive sleep apnea/hypoxia by polysomnography. At baseline, they had severe obstructive sleep apnea/hypoxia, elevated aminotransferases, the metabolic syndrome, and significant oxidative stress (high F(2)-isoprostanes). Obstructive sleep apnea/hypoxia was treated with home CPAP for a mean 89 ± 62 days. Although body mass index increased, obstructive sleep apnea/hypoxia severity improved on CPAP and was accompanied by reduced alanine aminotransferase, metabolic syndrome markers, and F(2)-isoprostanes.

Conclusions: This study provides strong evidence that treatment of obstructive sleep apnea/nocturnal hypoxia with CPAP in children with NAFLD may reverse parameters of liver injury and reduce oxidative stress. These data also suggest CPAP as a new therapy to prevent progression of NAFLD in those children with obesity found to have obstructive sleep apnea/nocturnal hypoxia.
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http://dx.doi.org/10.1016/j.jpeds.2018.03.028DOI Listing
July 2018

Frailty in Children with Liver Disease: A Prospective Multicenter Study.

J Pediatr 2018 03;194:109-115.e4

Division of Gastroenterology, Hepatology and Nutrition, Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatric, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Objective: To assess frailty, a measure of physiologic declines in multiple organ systems, in children with chronic liver disease using a novel pediatric frailty tool.

Study Design: We performed a prospective cross-sectional multicenter study at 17 liver transplantation (LT) centers. 71 children (5-17 years of age), 36 with compensated chronic liver disease (CCLD) and 35 with end-stage liver disease (ESLD) and listed for LT, were assessed for frailty using validated pediatric tools to assess the 5 classic Fried Frailty Criteria-slowness, weakness, exhaustion, diminished physical activity, and shrinkage. Test scores were translated to age- and sex-dependent z scores, generating a maximum frailty score of 10.

Results: The median frailty score of the cohort was 4 (IQR 3, 5). Subjects with ESLD had significantly higher frailty scores (median 5; IQR 4, 7) than subjects with CCLD (median 3; IQR 2, 4); (P <  .0001). Area under the curve receiver operating characteristic for frailty scores to discriminate between ESLD and CCLD was 0.83 (95% CI 0.73, 0.93). Forty-six percent of children with ESLD were frail and there was no correlation between pediatric frailty scores and physician's global assessments (r = -0.24, 95% CI -0.53, 0.10).

Conclusions: A novel frailty tool assessed additional dimensions of health, not captured by standard laboratory measures and identified the sickest individuals among a cohort of children with chronic liver disease. This tool may have applicability to other children with chronic disease.
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http://dx.doi.org/10.1016/j.jpeds.2017.10.066DOI Listing
March 2018

Nutritional State and Feeding Behaviors of Children With Eosinophilic Esophagitis and Gastroesophageal Reflux Disease.

J Pediatr Gastroenterol Nutr 2018 04;66(4):603-608

Gastrointestinal Eosinophilic Diseases Program.

Objective: As both gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) are associated with malnutrition and feeding dysfunction, this study compares growth, nutrition, and feeding behaviors in children with GERD and EoE.

Methods: Subjects ages 1 to 7 years with GERD or EoE were enrolled in a prospective study. Assessments included length/height, weight, 3-day food diary, serum biomarkers of nutrition, and the Behavioral Pediatric Feeding Assessment Scale.

Results: Mean weight-for-length z scores in GERD and EoE children were -0.93 and -1.14 (p = NS) and mean body mass index z scores were 0.29 and -0.13 (P = NS). Vitamin D intake was below the daily recommended intake in GERD subjects. EoE subjects' intake was below daily recommended intake of Vitamin D and calcium. GERD and EoE groups both had normal intake of calories, carbohydrates, proteins, fats, and iron, and normal serum ferritin (25 vs 34 ng/mL), prealbumin (21 vs 20 mg/dL), parathyroid hormone (42 vs 37 pg/mL), and Vitamin D (both 30 ng/mL). Behavioral Pediatric Feeding Assessment Scale problem and frequency scores were similar in GERD and EoE subjects but were higher than those of a historical cohort of healthy controls (Hedges' g of 0.95 and 1.1, respectively). EoE subjects on food allergen restriction diets had significantly less feeding dysfunction than those on regular diets.

Conclusions: As a selected group of children with uncomplicated GERD or EoE were without nutritional deficiencies but had maladaptive feeding, providing anticipatory guidance to minimize mealtime challenges, monitoring for improvement, or referring to a feeding therapist, may be beneficial. A trial of food allergen restriction may provide additional benefit for those with EoE.
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http://dx.doi.org/10.1097/MPG.0000000000001741DOI Listing
April 2018

Outcomes in Pediatric Autoimmune Hepatitis and Significance of Azathioprine Metabolites.

J Pediatr Gastroenterol Nutr 2017 07;65(1):80-85

*Department of Pediatrics, University of Colorado School of Medicine†Digestive Health Institute, Children's Hospital Colorado‡Department of Pathology, University of Colorado School of Medicine§Department of Pathology, Children's Hospital Colorado||Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora, CO.

Objectives: Autoimmune hepatitis (AIH) is a common pediatric liver disease and long-term remission is usually maintained with azathioprine (AZA). There is no consensus on the target range for AZA active metabolite 6-thioguanine (6-TGN) levels in pediatric AIH. The aim of the present study was to characterize the outcomes of pediatric patients with AIH and determine correlations between AZA dosing or 6-TGN metabolite levels and biochemical remission.

Methods: A retrospective chart review was performed and data on presentation, laboratories including AZA metabolite levels, medication use, and outcomes were collected.

Results: Between 2002 and 2013, 66 children with AIH were identified (mean age at diagnosis 9.6 ± 5.1 years) with a mean follow-up period of 2.9 ± 3.2 years. Common presenting symptoms included jaundice, fatigue, and abdominal pain. The majority of subjects received steroids for induction and AZA for maintenance of remission. Seventy-nine percent achieved biochemical remission (mean time to remission 6.2 ± 9.2 months), 14% were in the induction phase of therapy, 6% required liver transplantation, and 18% were weaned off immunosuppression and remained in remission. 6-TGN levels ranging from 50 to 250 pmol/8 × 10 red blood cell count were associated with biochemical remission (alanine aminotransferase levels of ≤50 U/L).

Conclusions: The vast majority of children with AIH maintain a sustained remission with AZA monotherapy. Biochemical remission was maintained with 6-TGN levels much lower than that recommended for inflammatory bowel disease. These findings suggest that patients should be maintained at the lowest AZA dose possible that is associated with biochemical remission.
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http://dx.doi.org/10.1097/MPG.0000000000001563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482766PMC
July 2017

NASPGHAN Clinical Practice Guideline for the Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease in Children: Recommendations from the Expert Committee on NAFLD (ECON) and the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN).

J Pediatr Gastroenterol Nutr 2017 02;64(2):319-334

*School of Medicine, Emory University †Children's Healthcare of Atlanta, Atlanta, GA ‡Texas Children's Hospital §Baylor College of Medicine, Houston, TX ||School of Medicine, Yale University, New Haven, CT ¶School of Medicine, University of Colorado, Denver #Children's Hospital Colorado, Aurora, CO **Cincinnati Children's Hospital Medical Center ††Department of Pediatrics, University of Cincinnati, Cincinnati, OH ‡‡Hospital for Sick Children §§School of Medicine, University of Toronto, Toronto ||||Janeway Children's Health and Rehabilitation Centre ¶¶Discipline of Pediatrics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada ##School of Medicine, University of California San Diego ***Rady Children's Hospital, San Diego, CA.

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that occurs in the setting of insulin resistance and increased adiposity. It has rapidly evolved into the most common liver disease seen in the pediatric population and is a management challenge for general pediatric practitioners, subspecialists, and for health systems. In this guideline, the expert committee on NAFLD reviewed and summarized the available literature, formulating recommendations to guide screening and clinical care of children with NAFLD.
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http://dx.doi.org/10.1097/MPG.0000000000001482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413933PMC
February 2017

Hospitalizations for Respiratory Syncytial Virus and Vaccine-Preventable Infections in the First 2 Years After Pediatric Liver Transplant.

J Pediatr 2017 03 11;182:232-238.e1. Epub 2017 Jan 11.

Adult and Child Consortium for Health Outcomes Research and Delivery Science, Anschutz Medical Campus & Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO; Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO.

Objectives: To examine in liver transplant recipients at centers participating in the Pediatric Health Information System dataset the number of hospitalizations for respiratory syncytial virus (RSV) and vaccine-preventable infections (VPIs) in the first 2 years after transplantation, morbidity and mortality associated with these hospitalizations, and costs associated with these hospitalizations.

Study Design: A retrospective cohort study of patients <18 years of age who underwent liver transplantation at a Pediatric Health Information System center between January 1, 2004, and December 31, 2012. Hospitalizations for RSV/VPIs during the first 2 years post-transplant were ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Data were collected on clinical care, outcomes, and costs during these hospitalizations.

Results: There were 2554 liver transplant recipients identified; 415 patients (16.3%) had 544 cases of RSV/VPIs. RSV, rotavirus, and influenza were the most common infections resulting in hospitalization. Ninety-two patients (3.6%) had RSV/VPI during their transplant hospitalization. Transplant hospitalizations complicated by RSV/VPI were longer (44 days vs. 21 days; P < .001), had higher rejection rates (37% vs. 26%; P = .02), and were more expensive ($259 697 vs. $190 860; P < .001). Multivariate analyses identified age <2 years at transplant (P < .001) and multivisceral recipient (P = .04) as predictors of a hospitalization for RSV.

Conclusions: VPIs occurred in 1 of 6 liver transplant recipients in the first 2 years post-transplant, a significantly higher rate than in the general pediatric population. These hospitalizations had substantial morbidity, mortality, and costs, demonstrating the importance of vaccinating patients before transplantation.
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http://dx.doi.org/10.1016/j.jpeds.2016.12.021DOI Listing
March 2017
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