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Jorge A. Bezerra - One of the best experts on this subject based on the ideXlab platform.

  • Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy.
    Hepatology communications, 2019
    Co-Authors: Jeffrey S. Moore, Joseph Bednarek, Jorge A. Bezerra, Catherine J. Goodhue, Saul J. Karpen, Kathleen M. Loomes, John C. Magee, Estella M. Alonso, Vicky L. Ng
    Abstract:

    Biliary atresia is a progressive fibroinflammatory cholangiopathy of infancy that is associated with activation of innate and adaptive immune responses targeting bile ducts. A recently completed multicenter phase I/IIA trial of intravenous immunoglobulin in biliary atresia did not improve serum total bilirubin levels at 90 days after Hepatoportoenterostomy or survival with the native liver at 1 year. A mechanistic aim of this trial was to determine if the peripheral blood immunophenotype was associated with clinical outcomes. Flow cytometry of peripheral blood cell markers (natural killer [NK], macrophage subsets, T- and B-cell subsets, regulatory T cells), neutrophils, and activation markers (clusters of differentiation [CD]38, CD69, CD86, human leukocyte antigen-DR isotype [HLA-DR]) was performed on 29 patients with biliary atresia at baseline and at 60, 90, 180, and 360 days after Hepatoportoenterostomy. Plasma cytokines and neutrophil products were also measured. Spearman correlations of change of an immune marker from baseline to day 90 with change in serum bilirubin revealed that an increase in total bilirubin correlated with 1) increased percentage of HLA-DR+CD38+ NK cells and expression of NK cell activation markers CD69 and HLA-DR, 2) decreased percentage of regulatory T cells, and 3) increased interleukin (IL)-8 and associated neutrophil products (elastase and neutrophil extracellular traps). Cox modeling revealed that the change from baseline to day 60 of the percentage of HLA-DR+CD38+ NK cells and plasma IL-8 levels was associated with an increased risk of transplant or death by day 360. Conclusion: Poor outcomes in biliary atresia correlated with higher peripheral blood NK cells and IL-8 and lower regulatory T cells. Future studies should include immunotherapies targeting these pathways in order to protect the biliary tree from ongoing damage.

  • Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study.
    The Journal of pediatrics, 2018
    Co-Authors: Lisa G. Sorensen, Saul J. Karpen, Estella M. Alonso, Jeffrey S. Moore, Emily M. Fredericks, Benjamin L. Shneider, Jean P. Molleston, Jorge A. Bezerra
    Abstract:

    Objectives To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. Study design Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and Results There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P = .01) and low length z-scores at time of testing (OR, 0.70; P  Conclusion Participants with biliary atresia surviving with native livers after Hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful Hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful Hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions. Trial registration Clinicaltrials.gov : NCT00061828 and NCT00294684.

  • total serum bilirubin within 3 months of Hepatoportoenterostomy predicts short term outcomes in biliary atresia
    The Journal of Pediatrics, 2016
    Co-Authors: Benjamin L. Shneider, Jorge A. Bezerra, Saul J. Karpen, John C. Magee, Elizabeth B. Rand, Kathleen B Schwarz, Michael R Narkewicz, Lee M Bass, Peter F Whitington, Nanda Kerkar
    Abstract:

    Objectives To prospectively assess the value of serum total bilirubin (TB) within 3 months of Hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. Study design Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB Results Fifty percent (68/137) of infants had TB P P P P P  = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P P Conclusions Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB Trial registration ClinicalTrials.gov: NCT00061828 and NCT00294684.

  • pathogenesis of biliary atresia defining biology to understand clinical phenotypes
    Nature Reviews Gastroenterology & Hepatology, 2015
    Co-Authors: Akihiro Asai, Alexander Miethke, Jorge A. Bezerra
    Abstract:

    Biliary atresia is a severe cholangiopathy of early infancy that destroys extrahepatic bile ducts and disrupts bile flow. With a poorly defined disease pathogenesis, treatment consists of the surgical removal of duct remnants followed by Hepatoportoenterostomy. Although this approach can improve the short-term outcome, the liver disease progresses to end-stage cirrhosis in most children. Further improvement in outcome will require a greater understanding of the mechanisms of biliary injury and fibrosis. Here, we review progress in the field, which has been fuelled by collaborative studies in larger patient cohorts and the development of cell culture and animal model systems to directly test hypotheses. Advances include the identification of phenotypic subgroups and stages of disease based on clinical, pathological and molecular features. Stronger evidence exists for viruses, toxins and gene sequence variations in the aetiology of biliary atresia, triggering a proinflammatory response that injures the duct epithelium and produces a rapidly progressive cholangiopathy. The immune response also activates the expression of type 2 cytokines that promote epithelial cell proliferation and extracellular matrix production by nonparenchymal cells. These advances provide insight into phenotype variability and might be relevant to the design of personalized trials to block progression of liver disease.

  • use of corticosteroids after Hepatoportoenterostomy for bile drainage in infants with biliary atresia the start randomized clinical trial
    JAMA, 2014
    Co-Authors: Jorge A. Bezerra, John C. Magee, Benjamin L. Shneider, Barbara A. Haber, Jessi Erlichman, Philip J. Rosenthal, Cathie Spino, Kasper S Wang, Paula M Hertel
    Abstract:

    Importance Biliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after Hepatoportoenterostomy improves clinical outcome. Objective To determine whether the addition of high-dose corticosteroids after Hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver. Design, Setting, and Patients The multicenter, double-blind Steroids in Biliary Atresia Randomized Trial (START) was conducted in 140 infants (mean age, 2.3 months) between September 2005 and February 2011 in the United States; follow-up ended in January 2013. Interventions Participants were randomized to receive intravenous methylprednisolone (4 mg/kg/d for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks) followed by a tapering protocol for 9 weeks (n = 70) or placebo (n = 70) initiated within 72 hours of Hepatoportoenterostomy. Main Outcomes and Measures The primary end point (powered to detect a 25% absolute treatment difference) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months postHepatoportoenterostomy. Secondary outcomes included survival with native liver at 24 months of age and serious adverse events. Results The proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months postHepatoportoenterostomy (58.6% [41/70] of steroids group vs 48.6% [34/70] of placebo group; adjusted relative risk, 1.14 [95% CI, 0.83 to 1.57]; P  = .43). The adjusted absolute risk difference was 8.7% (95% CI, −10.4% to 27.7%). Transplant-free survival was 58.7% in the steroids group vs 59.4% in the placebo group (adjusted hazard ratio, 1.0 [95% CI, 0.6 to 1.8]; P  = .99) at 24 months of age. The percentage of participants with serious adverse events was 81.4% [57/70] of the steroids group and 80.0% [56/70] of the placebo group ( P  > .99); however, participants receiving steroids had an earlier time of onset of their first serious adverse event by 30 days postHepatoportoenterostomy (37.2% [95% CI, 26.9% to 50.0%] of steroids group vs 19.0% [95% CI, 11.5% to 30.4%] of placebo group; P  = .008). Conclusions and Relevance Among infants with biliary atresia who have undergone Hepatoportoenterostomy, high-dose steroid therapy following surgery did not result in statistically significant treatment differences in bile drainage at 6 months, although a small clinical benefit could not be excluded. Steroid treatment was associated with earlier onset of serious adverse events in children with biliary atresia. Trial Registration clinicaltrials.gov Identifier:NCT00294684

Benjamin L. Shneider - One of the best experts on this subject based on the ideXlab platform.

  • Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study.
    The Journal of pediatrics, 2018
    Co-Authors: Lisa G. Sorensen, Saul J. Karpen, Estella M. Alonso, Jeffrey S. Moore, Emily M. Fredericks, Benjamin L. Shneider, Jean P. Molleston, Jorge A. Bezerra
    Abstract:

    Objectives To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. Study design Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and Results There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P = .01) and low length z-scores at time of testing (OR, 0.70; P  Conclusion Participants with biliary atresia surviving with native livers after Hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful Hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful Hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions. Trial registration Clinicaltrials.gov : NCT00061828 and NCT00294684.

  • total serum bilirubin within 3 months of Hepatoportoenterostomy predicts short term outcomes in biliary atresia
    The Journal of Pediatrics, 2016
    Co-Authors: Benjamin L. Shneider, Jorge A. Bezerra, Saul J. Karpen, John C. Magee, Elizabeth B. Rand, Kathleen B Schwarz, Michael R Narkewicz, Lee M Bass, Peter F Whitington, Nanda Kerkar
    Abstract:

    Objectives To prospectively assess the value of serum total bilirubin (TB) within 3 months of Hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. Study design Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB Results Fifty percent (68/137) of infants had TB P P P P P  = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P P Conclusions Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB Trial registration ClinicalTrials.gov: NCT00061828 and NCT00294684.

  • Liver Transplantation for Biliary Atresia: Is There a Difference in Outcome for Infants?
    Journal of pediatric gastroenterology and nutrition, 2016
    Co-Authors: Ronen Arnon, Rachel A. Annunziato, Guiseppe D’amelio, Jaime Chu, Benjamin L. Shneider
    Abstract:

    ABSTRACTObjectives:Liver transplantation (LT) in children with biliary atresia (BA) is often performed because of poor bile drainage, complications of biliary cirrhosis, or recurrent cholangitis. Poor bile drainage after a Kasai Hepatoportoenterostomy is the primary driver for LT in infancy. The aim

  • use of corticosteroids after Hepatoportoenterostomy for bile drainage in infants with biliary atresia the start randomized clinical trial
    JAMA, 2014
    Co-Authors: Jorge A. Bezerra, John C. Magee, Benjamin L. Shneider, Barbara A. Haber, Jessi Erlichman, Philip J. Rosenthal, Cathie Spino, Kasper S Wang, Paula M Hertel
    Abstract:

    Importance Biliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after Hepatoportoenterostomy improves clinical outcome. Objective To determine whether the addition of high-dose corticosteroids after Hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver. Design, Setting, and Patients The multicenter, double-blind Steroids in Biliary Atresia Randomized Trial (START) was conducted in 140 infants (mean age, 2.3 months) between September 2005 and February 2011 in the United States; follow-up ended in January 2013. Interventions Participants were randomized to receive intravenous methylprednisolone (4 mg/kg/d for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks) followed by a tapering protocol for 9 weeks (n = 70) or placebo (n = 70) initiated within 72 hours of Hepatoportoenterostomy. Main Outcomes and Measures The primary end point (powered to detect a 25% absolute treatment difference) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months postHepatoportoenterostomy. Secondary outcomes included survival with native liver at 24 months of age and serious adverse events. Results The proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months postHepatoportoenterostomy (58.6% [41/70] of steroids group vs 48.6% [34/70] of placebo group; adjusted relative risk, 1.14 [95% CI, 0.83 to 1.57]; P  = .43). The adjusted absolute risk difference was 8.7% (95% CI, −10.4% to 27.7%). Transplant-free survival was 58.7% in the steroids group vs 59.4% in the placebo group (adjusted hazard ratio, 1.0 [95% CI, 0.6 to 1.8]; P  = .99) at 24 months of age. The percentage of participants with serious adverse events was 81.4% [57/70] of the steroids group and 80.0% [56/70] of the placebo group ( P  > .99); however, participants receiving steroids had an earlier time of onset of their first serious adverse event by 30 days postHepatoportoenterostomy (37.2% [95% CI, 26.9% to 50.0%] of steroids group vs 19.0% [95% CI, 11.5% to 30.4%] of placebo group; P  = .008). Conclusions and Relevance Among infants with biliary atresia who have undergone Hepatoportoenterostomy, high-dose steroid therapy following surgery did not result in statistically significant treatment differences in bile drainage at 6 months, although a small clinical benefit could not be excluded. Steroid treatment was associated with earlier onset of serious adverse events in children with biliary atresia. Trial Registration clinicaltrials.gov Identifier:NCT00294684

  • efficacy of fat soluble vitamin supplementation in infants with biliary atresia
    Pediatrics, 2012
    Co-Authors: Benjamin L. Shneider, Jorge A. Bezerra, Saul J. Karpen, John C. Magee, Barbara A. Haber, Philip J. Rosenthal, Trivellore E Raghunathan, Kathleen B Schwarz, Frederick J Suchy, Nanda Kerkar
    Abstract:

    OBJECTIVE: Cholestasis predisposes to fat-soluble vitamin (FSV) deficiencies. A liquid multiple FSV preparation made with tocopheryl polyethylene glycol-1000 succinate (TPGS) is frequently used in infants with biliary atresia (BA) because of ease of administration and presumed efficacy. In this prospective multicenter study, we assessed the prevalence of FSV deficiency in infants with BA who received this FSV/TPGS preparation. METHODS: Infants received FSV/TPGS coadministered with additional vitamin K as routine clinical care in a randomized double-blinded, placebo-controlled trial of corticosteroid therapy after Hepatoportoenterostomy (HPE) for BA (identifier NCT 00294684). Levels of FSV, retinol binding protein, total serum lipids, and total bilirubin (TB) were measured 1, 3, and 6 months after HPE. RESULTS: Ninety-two infants with BA were enrolled in this study. Biochemical evidence of FSV insufficiency was common at all time points for vitamin A (29%–36% of patients), vitamin D (21%–37%), vitamin K (10%–22%), and vitamin E (16%–18%). Vitamin levels were inversely correlated with serum TB levels. Biochemical FSV insufficiency was much more common (15%–100% for the different vitamins) in infants whose TB was ≥2 mg/dL. At 3 and 6 months post HPE, only 3 of 24 and 0 of 23 infants, respectively, with TB >2 mg/dL were sufficient in all FSV. CONCLUSIONS: Biochemical FSV insufficiency is commonly observed in infants with BA and persistent cholestasis despite administration of a TPGS containing liquid multiple FSV preparation. Individual vitamin supplementation and careful monitoring are warranted in infants with BA, especially those with TB >2 mg/dL. * Abbreviations: BA — : biliary atresia FSV — : fat-soluble vitamin HPE — : Hepatoportoenterostomy INR — : international normalized ratio RBP — : retinol binding protein TB — : total bilirubin TPGS — : D-α tocopheryl polyethylene glycol-1000 succinate

Kathleen B Schwarz - One of the best experts on this subject based on the ideXlab platform.

  • Factors Associated with Timing and Adverse Outcomes in Patients with Biliary Atresia Undergoing Kasai Hepatoportoenterostomy.
    The Journal of pediatrics, 2018
    Co-Authors: Michael Ross Townsend, Adeeb Jaber, Hanina Abi Nader, Shaker M. Eid, Kathleen B Schwarz
    Abstract:

    Objective To assess factors associated with timing of Hepatoportoenterostomy (HPE) and adverse perioperative outcomes in patients with biliary atresia in the US. Study design We examined hospitalizations in infants aged Results Our analysis of 1243 biliary atresia hospitalizations showed that only 37.7% of patients had HPE in the first 60 days of life. Patients who underwent HPE after 60 days of age were uninsured, were more likely to be black (aOR, 4.22; 95% CI, 1.49-11.95), less likely to be admitted at a teaching hospital (aOR, 0.27; 95% CI 0.10-0.79), and less likely to have a concomitant congenital malformation (aOR, 0.49; 95% CI 0.25-0.98). Patients with delayed age at HPE incurred significantly higher hospital costs ($57 914 vs $34 074; P = .026). Delayed age at HPE and weekend admission were independently associated with increased odds of adverse perioperative outcome (aOR, 1.09; 95% CI, 1.01-3.02 and 3.98; 95% CI, 1.67-9.46, respectively). Conclusion Current outcomes in patients with biliary atresia in the United States are suboptimal and result in higher costs. The specific factors associated with delayed care are further evidence that universal health care and screening are needed for all infants, along with systematic referral of potential patients with biliary atresia to specialized health centers.

  • Percutaneous Transhepatic Cholangioplasty to Treat Multiple Intrahepatic Biliary Strictures After Hepatoportoenterostomy.
    Journal of pediatric gastroenterology and nutrition, 2017
    Co-Authors: Melissa Weidner, Sally E. Mitchell, Kathleen B Schwarz
    Abstract:

    In children with biliary atresia, Hepatoportoenterostomy (HP) is recommended to improve bile flow. Biliary strictures are known potential complications after HP, which can again impair bile flow often leading to biliary cirrhosis and liver transplantation. In patients who are status post HP and have biliary strictures, nonsurgical therapeutic options such as endoscopic dilation can pose technical difficulties due to altered anatomy. Percutaneous transhepatic cholangiography with cholangioplasty is a valuable tool for obstructive cholangiopathies, but to our knowledge this has not been previously demonstrated to be successful in patients with multiple intrahepatic biliary strictures status post HP. Herein, we present 3 patients status post HP who presented with multiple intrahepatic biliary strictures and underwent successful percutaneous transhepatic cholangiography with cholangioplasty.

  • total serum bilirubin within 3 months of Hepatoportoenterostomy predicts short term outcomes in biliary atresia
    The Journal of Pediatrics, 2016
    Co-Authors: Benjamin L. Shneider, Jorge A. Bezerra, Saul J. Karpen, John C. Magee, Elizabeth B. Rand, Kathleen B Schwarz, Michael R Narkewicz, Lee M Bass, Peter F Whitington, Nanda Kerkar
    Abstract:

    Objectives To prospectively assess the value of serum total bilirubin (TB) within 3 months of Hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. Study design Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB Results Fifty percent (68/137) of infants had TB P P P P P  = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P P Conclusions Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB Trial registration ClinicalTrials.gov: NCT00061828 and NCT00294684.

  • efficacy of fat soluble vitamin supplementation in infants with biliary atresia
    Pediatrics, 2012
    Co-Authors: Benjamin L. Shneider, Jorge A. Bezerra, Saul J. Karpen, John C. Magee, Barbara A. Haber, Philip J. Rosenthal, Trivellore E Raghunathan, Kathleen B Schwarz, Frederick J Suchy, Nanda Kerkar
    Abstract:

    OBJECTIVE: Cholestasis predisposes to fat-soluble vitamin (FSV) deficiencies. A liquid multiple FSV preparation made with tocopheryl polyethylene glycol-1000 succinate (TPGS) is frequently used in infants with biliary atresia (BA) because of ease of administration and presumed efficacy. In this prospective multicenter study, we assessed the prevalence of FSV deficiency in infants with BA who received this FSV/TPGS preparation. METHODS: Infants received FSV/TPGS coadministered with additional vitamin K as routine clinical care in a randomized double-blinded, placebo-controlled trial of corticosteroid therapy after Hepatoportoenterostomy (HPE) for BA (identifier NCT 00294684). Levels of FSV, retinol binding protein, total serum lipids, and total bilirubin (TB) were measured 1, 3, and 6 months after HPE. RESULTS: Ninety-two infants with BA were enrolled in this study. Biochemical evidence of FSV insufficiency was common at all time points for vitamin A (29%–36% of patients), vitamin D (21%–37%), vitamin K (10%–22%), and vitamin E (16%–18%). Vitamin levels were inversely correlated with serum TB levels. Biochemical FSV insufficiency was much more common (15%–100% for the different vitamins) in infants whose TB was ≥2 mg/dL. At 3 and 6 months post HPE, only 3 of 24 and 0 of 23 infants, respectively, with TB >2 mg/dL were sufficient in all FSV. CONCLUSIONS: Biochemical FSV insufficiency is commonly observed in infants with BA and persistent cholestasis despite administration of a TPGS containing liquid multiple FSV preparation. Individual vitamin supplementation and careful monitoring are warranted in infants with BA, especially those with TB >2 mg/dL. * Abbreviations: BA — : biliary atresia FSV — : fat-soluble vitamin HPE — : Hepatoportoenterostomy INR — : international normalized ratio RBP — : retinol binding protein TB — : total bilirubin TPGS — : D-α tocopheryl polyethylene glycol-1000 succinate

  • a multicenter study of the outcome of biliary atresia in the united states 1997 to 2000
    The Journal of Pediatrics, 2006
    Co-Authors: Benjamin L. Shneider, Jorge A. Bezerra, Barbara A. Haber, Philip J. Rosenthal, R W Shepherd, Kathleen B Schwarz, Peter F Whitington, Morton B Brown, Robert H Squires, Jay H Hoofnagle
    Abstract:

    Objective To determine the prognostic factors and optimal approaches to the diagnosis and management of biliary atresia, the leading indication for liver transplantation in children. Study design A retrospective study was performed of all children who underwent Hepatoportoenterostomy (HPE) for biliary atresia between 1997 and 2000 at 9 centers in the United States. Outcome at age 24 months was correlated with demographic and clinical parameters. Results A total of 104 children underwent HPE; 25% had congenital anomalies, and outcome was worse in those with biliary atresia splenic malformation syndrome. Diagnostic and clinical approaches varied, although specific approaches did not appear to correlate with outcome. The average age at referral was 53 days, and the average age at HPE was 61 days. At age 24 months, 58 children were alive with their native liver, 42 had undergone liver transplantation (37 alive, 5 dead), and 4 had died without undergoing transplantation. Kaplan-Meier analysis of survival without liver transplantation revealed markedly improved survival in children with total bilirubin level P Conclusions Outcome in the study centers was equivalent to that reported in other countries. Total bilirubin in early follow-up after HPE was highly predictive of outcome. Efforts to improve bile flow after HPE may lead to improved outcome in children with biliary atresia.

Nanda Kerkar - One of the best experts on this subject based on the ideXlab platform.

  • impact of steroid therapy on early growth in infants with biliary atresia the multicenter steroids in biliary atresia randomized trial
    The Journal of Pediatrics, 2018
    Co-Authors: Estella M. Alonso, Saul J. Karpen, Kathleen M. Loomes, Jean P. Molleston, Cara L. Mack, Paula M Hertel, Nanda Kerkar, Kieran Hawthorne, Veena Venkat, Karen F Murray
    Abstract:

    Objective To investigate the impact of corticosteroid therapy on the growth of participants in the Steroids in Biliary Atresia Randomized Trial (START) conducted through the Childhood Liver Disease Research Network. The primary analysis in START indicated that steroids did not have a beneficial effect on drainage in a cohort of infants with biliary atresia. We hypothesized that steroids would have a detrimental effect on growth in these infants. Study design A total of 140 infants were enrolled in START, with 70 randomized to each treatment arm: steroid and placebo. Length, weight, and head circumference were obtained at baseline and follow-up visits to 24 months of age. Results Patients treated with steroids had significantly lower length and head circumference z scores during the first 3 months post-Hepatoportoenterostomy (HPE), and significantly lower weight until 12 months. Growth trajectories in the steroid and placebo arms differed significantly for length (P  Conclusions Steroid therapy following HPE in patients with biliary atresia is associated with impaired length, weight, and head circumference growth trajectories for at least 6 months post-HPE, especially impacting infants with successful bile drainage. Trial registration ClinicalTrials.gov : NCT00294684 .

  • total serum bilirubin within 3 months of Hepatoportoenterostomy predicts short term outcomes in biliary atresia
    The Journal of Pediatrics, 2016
    Co-Authors: Benjamin L. Shneider, Jorge A. Bezerra, Saul J. Karpen, John C. Magee, Elizabeth B. Rand, Kathleen B Schwarz, Michael R Narkewicz, Lee M Bass, Peter F Whitington, Nanda Kerkar
    Abstract:

    Objectives To prospectively assess the value of serum total bilirubin (TB) within 3 months of Hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. Study design Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB Results Fifty percent (68/137) of infants had TB P P P P P  = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P P Conclusions Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB Trial registration ClinicalTrials.gov: NCT00061828 and NCT00294684.

  • efficacy of fat soluble vitamin supplementation in infants with biliary atresia
    Pediatrics, 2012
    Co-Authors: Benjamin L. Shneider, Jorge A. Bezerra, Saul J. Karpen, John C. Magee, Barbara A. Haber, Philip J. Rosenthal, Trivellore E Raghunathan, Kathleen B Schwarz, Frederick J Suchy, Nanda Kerkar
    Abstract:

    OBJECTIVE: Cholestasis predisposes to fat-soluble vitamin (FSV) deficiencies. A liquid multiple FSV preparation made with tocopheryl polyethylene glycol-1000 succinate (TPGS) is frequently used in infants with biliary atresia (BA) because of ease of administration and presumed efficacy. In this prospective multicenter study, we assessed the prevalence of FSV deficiency in infants with BA who received this FSV/TPGS preparation. METHODS: Infants received FSV/TPGS coadministered with additional vitamin K as routine clinical care in a randomized double-blinded, placebo-controlled trial of corticosteroid therapy after Hepatoportoenterostomy (HPE) for BA (identifier NCT 00294684). Levels of FSV, retinol binding protein, total serum lipids, and total bilirubin (TB) were measured 1, 3, and 6 months after HPE. RESULTS: Ninety-two infants with BA were enrolled in this study. Biochemical evidence of FSV insufficiency was common at all time points for vitamin A (29%–36% of patients), vitamin D (21%–37%), vitamin K (10%–22%), and vitamin E (16%–18%). Vitamin levels were inversely correlated with serum TB levels. Biochemical FSV insufficiency was much more common (15%–100% for the different vitamins) in infants whose TB was ≥2 mg/dL. At 3 and 6 months post HPE, only 3 of 24 and 0 of 23 infants, respectively, with TB >2 mg/dL were sufficient in all FSV. CONCLUSIONS: Biochemical FSV insufficiency is commonly observed in infants with BA and persistent cholestasis despite administration of a TPGS containing liquid multiple FSV preparation. Individual vitamin supplementation and careful monitoring are warranted in infants with BA, especially those with TB >2 mg/dL. * Abbreviations: BA — : biliary atresia FSV — : fat-soluble vitamin HPE — : Hepatoportoenterostomy INR — : international normalized ratio RBP — : retinol binding protein TB — : total bilirubin TPGS — : D-α tocopheryl polyethylene glycol-1000 succinate

Saul J. Karpen - One of the best experts on this subject based on the ideXlab platform.

  • Correlation of Immune Markers With Outcomes in Biliary Atresia Following Intravenous Immunoglobulin Therapy.
    Hepatology communications, 2019
    Co-Authors: Jeffrey S. Moore, Joseph Bednarek, Jorge A. Bezerra, Catherine J. Goodhue, Saul J. Karpen, Kathleen M. Loomes, John C. Magee, Estella M. Alonso, Vicky L. Ng
    Abstract:

    Biliary atresia is a progressive fibroinflammatory cholangiopathy of infancy that is associated with activation of innate and adaptive immune responses targeting bile ducts. A recently completed multicenter phase I/IIA trial of intravenous immunoglobulin in biliary atresia did not improve serum total bilirubin levels at 90 days after Hepatoportoenterostomy or survival with the native liver at 1 year. A mechanistic aim of this trial was to determine if the peripheral blood immunophenotype was associated with clinical outcomes. Flow cytometry of peripheral blood cell markers (natural killer [NK], macrophage subsets, T- and B-cell subsets, regulatory T cells), neutrophils, and activation markers (clusters of differentiation [CD]38, CD69, CD86, human leukocyte antigen-DR isotype [HLA-DR]) was performed on 29 patients with biliary atresia at baseline and at 60, 90, 180, and 360 days after Hepatoportoenterostomy. Plasma cytokines and neutrophil products were also measured. Spearman correlations of change of an immune marker from baseline to day 90 with change in serum bilirubin revealed that an increase in total bilirubin correlated with 1) increased percentage of HLA-DR+CD38+ NK cells and expression of NK cell activation markers CD69 and HLA-DR, 2) decreased percentage of regulatory T cells, and 3) increased interleukin (IL)-8 and associated neutrophil products (elastase and neutrophil extracellular traps). Cox modeling revealed that the change from baseline to day 60 of the percentage of HLA-DR+CD38+ NK cells and plasma IL-8 levels was associated with an increased risk of transplant or death by day 360. Conclusion: Poor outcomes in biliary atresia correlated with higher peripheral blood NK cells and IL-8 and lower regulatory T cells. Future studies should include immunotherapies targeting these pathways in order to protect the biliary tree from ongoing damage.

  • impact of steroid therapy on early growth in infants with biliary atresia the multicenter steroids in biliary atresia randomized trial
    The Journal of Pediatrics, 2018
    Co-Authors: Estella M. Alonso, Saul J. Karpen, Kathleen M. Loomes, Jean P. Molleston, Cara L. Mack, Paula M Hertel, Nanda Kerkar, Kieran Hawthorne, Veena Venkat, Karen F Murray
    Abstract:

    Objective To investigate the impact of corticosteroid therapy on the growth of participants in the Steroids in Biliary Atresia Randomized Trial (START) conducted through the Childhood Liver Disease Research Network. The primary analysis in START indicated that steroids did not have a beneficial effect on drainage in a cohort of infants with biliary atresia. We hypothesized that steroids would have a detrimental effect on growth in these infants. Study design A total of 140 infants were enrolled in START, with 70 randomized to each treatment arm: steroid and placebo. Length, weight, and head circumference were obtained at baseline and follow-up visits to 24 months of age. Results Patients treated with steroids had significantly lower length and head circumference z scores during the first 3 months post-Hepatoportoenterostomy (HPE), and significantly lower weight until 12 months. Growth trajectories in the steroid and placebo arms differed significantly for length (P  Conclusions Steroid therapy following HPE in patients with biliary atresia is associated with impaired length, weight, and head circumference growth trajectories for at least 6 months post-HPE, especially impacting infants with successful bile drainage. Trial registration ClinicalTrials.gov : NCT00294684 .

  • Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study.
    The Journal of pediatrics, 2018
    Co-Authors: Lisa G. Sorensen, Saul J. Karpen, Estella M. Alonso, Jeffrey S. Moore, Emily M. Fredericks, Benjamin L. Shneider, Jean P. Molleston, Jorge A. Bezerra
    Abstract:

    Objectives To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. Study design Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and Results There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P = .01) and low length z-scores at time of testing (OR, 0.70; P  Conclusion Participants with biliary atresia surviving with native livers after Hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful Hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful Hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions. Trial registration Clinicaltrials.gov : NCT00061828 and NCT00294684.

  • total serum bilirubin within 3 months of Hepatoportoenterostomy predicts short term outcomes in biliary atresia
    The Journal of Pediatrics, 2016
    Co-Authors: Benjamin L. Shneider, Jorge A. Bezerra, Saul J. Karpen, John C. Magee, Elizabeth B. Rand, Kathleen B Schwarz, Michael R Narkewicz, Lee M Bass, Peter F Whitington, Nanda Kerkar
    Abstract:

    Objectives To prospectively assess the value of serum total bilirubin (TB) within 3 months of Hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. Study design Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 μM) at any time in the first 3 months (TB Results Fifty percent (68/137) of infants had TB P P P P P  = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P P Conclusions Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB Trial registration ClinicalTrials.gov: NCT00061828 and NCT00294684.

  • efficacy of fat soluble vitamin supplementation in infants with biliary atresia
    Pediatrics, 2012
    Co-Authors: Benjamin L. Shneider, Jorge A. Bezerra, Saul J. Karpen, John C. Magee, Barbara A. Haber, Philip J. Rosenthal, Trivellore E Raghunathan, Kathleen B Schwarz, Frederick J Suchy, Nanda Kerkar
    Abstract:

    OBJECTIVE: Cholestasis predisposes to fat-soluble vitamin (FSV) deficiencies. A liquid multiple FSV preparation made with tocopheryl polyethylene glycol-1000 succinate (TPGS) is frequently used in infants with biliary atresia (BA) because of ease of administration and presumed efficacy. In this prospective multicenter study, we assessed the prevalence of FSV deficiency in infants with BA who received this FSV/TPGS preparation. METHODS: Infants received FSV/TPGS coadministered with additional vitamin K as routine clinical care in a randomized double-blinded, placebo-controlled trial of corticosteroid therapy after Hepatoportoenterostomy (HPE) for BA (identifier NCT 00294684). Levels of FSV, retinol binding protein, total serum lipids, and total bilirubin (TB) were measured 1, 3, and 6 months after HPE. RESULTS: Ninety-two infants with BA were enrolled in this study. Biochemical evidence of FSV insufficiency was common at all time points for vitamin A (29%–36% of patients), vitamin D (21%–37%), vitamin K (10%–22%), and vitamin E (16%–18%). Vitamin levels were inversely correlated with serum TB levels. Biochemical FSV insufficiency was much more common (15%–100% for the different vitamins) in infants whose TB was ≥2 mg/dL. At 3 and 6 months post HPE, only 3 of 24 and 0 of 23 infants, respectively, with TB >2 mg/dL were sufficient in all FSV. CONCLUSIONS: Biochemical FSV insufficiency is commonly observed in infants with BA and persistent cholestasis despite administration of a TPGS containing liquid multiple FSV preparation. Individual vitamin supplementation and careful monitoring are warranted in infants with BA, especially those with TB >2 mg/dL. * Abbreviations: BA — : biliary atresia FSV — : fat-soluble vitamin HPE — : Hepatoportoenterostomy INR — : international normalized ratio RBP — : retinol binding protein TB — : total bilirubin TPGS — : D-α tocopheryl polyethylene glycol-1000 succinate