Browsing by Author "Whitington, Peter F."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Extrahepatic anomalies in infants with biliary atresia: results of a large prospective North American multicenter study
    (Wiley, 2013-11) Schwarz, Kathleen B.; Haber, Barbara H.; Rosenthal, Philip; Mack, Cara L; Moore, Jeffrey; Bove, Kevin E.; Bezerra, Jorge A.; Karpen, Saul J.; Kerkar, Nanda; Shneider, Benjamin L.; Turmelle, Yumirle P.; Whitington, Peter F.; Molleston, Jean P.; Murray, Karen F.; Ng, Vicky L.; Romero, René; Wang, Kasper S.; Sokol, Ronald J.; Magee, John C.; Pediatrics, School of Medicine
    Background and aims The etiology of biliary atresia (BA) is unknown. Given that patterns of anomalies might provide etiopathogenetic clues, we utilized data from the North American Childhood Liver Disease Research and Education Network to analyze patterns of anomalies in infants with BA. Methods Two hundred eighty-nine infants who were enrolled into the prospective database prior to surgery at any of 15 centers participating were evaluated. Results Group 1 was non-syndromic, isolated BA (without major malformations) (n = 242, 84 %), Group 2 was BA and at least one malformation considered major as defined by the National Birth Defects Prevention Study but without laterality defects (n = 17, 6%). Group 3 was syndromic, with laterality defects (n = 30, 10%). In the population as a whole, anomalies (either major or minor) were most prevalent in the cardiovascular (16%) and gastrointestinal (14%) systems. Group 3 patients accounted for the majority of subjects with cardiac, gastrointestinal and splenic anomalies. Group 2 subjects also frequently displayed cardiovascular (71%) and gastrointestinal (24 %) anomalies; interestingly this group had genitourinary anomalies more frequently (47%) compared to Group 3 subjects (10%). Conclusions This study identified a group of BA (Group 2) that differed from the classical syndromic and non-syndromic groups and that was defined by multiple malformations without laterality defects. Careful phenotyping of the patterns of anomalies may be critical to the interpretation of both genetic and environmental risk factors associated with BA, allowing new insight into pathogenesis and/or outcome.
  • Thumbnail Image
    Item
    In Children with Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis is Associated with Advanced Fibrosis
    (Elsevier, 2017) Africa, Jonathan A.; Behling, Cynthia A.; Brunt, Elizabeth M.; Zhang, Nan; Luo, Yunjun; Wells, Alan; Hou, Jiayi; Belt, Patricia H.; Kohil, Rohit; Lavine, Joel E.; Molleston, Jean P.; Newton, Kimberly P.; Whitington, Peter F.; Schwimmer, Jeffrey B.; Department of Pediatrics, IU School of Medicine
    Background & Aims Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. Methods We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Results Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001). Conclusions Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis.
  • Thumbnail Image
    Item
    Total Serum Bilirubin within 3 Months of Hepatoportoenterostomy Predicts Short-Term Outcomes in Biliary Atresia
    (Elsevier, 2016-03) Shneider, Benjamin L.; Magee, John C.; Karpen, Saul J.; Rand, Elizabeth B.; Narkewicz, Michael R.; Bass, Lee M.; Schwarz, Kathleen; Whitington, Peter F.; Bezerra, Jorge A.; Kerkar, Nanda; Haber, Barbara; Rosenthal, Philip; Turmelle, Yumirle P.; Molleston, Jean P.; Murray, Karen F.; Nguyen, Vicky L.; Wang, Kasper S.; Romero, Rene; Squires, Robert H.; Arnon, Ronen; Sherker, Averell H.; Moore, Jeffrey; Ye, Wen; Sokol, Ronald J.; Department of Pediatrics, IU School of Medicine
    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 <2.0, all others TB ≥ 2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. RESULTS: Fifty percent (68/137) of infants had TB < 2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB < 2.0 group vs TB ≥ 2 (86% vs 20%, P < .0001). Infants with TB ≥ 2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). 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 <2.0 mg/dL within 3 months of HPE may enhance early outcomes.