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Browsing by Author "Hawthorne, Kieran"
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Item Impact of Steroid Therapy on Early Growth in Infants with Biliary Atresia: The Multicenter Steroids in Biliary Atresia Randomized Trial(Elsevier, 2018-11) Alonso, Estella M.; Ye, Wen; Hawthorne, Kieran; Venkat, Veena; Loomes, Kathleen M.; Mack, Cara L.; Hertel, Paula M.; Karpen, Saul J.; Kerkar, Nanda; Molleston, Jean P.; Murray, Karen F.; Romero, Rene; Rosenthal, Philip; Schwarz, Kathleen B.; Shneider, Benjamin L.; Suchy, Frederick J.; Turmelle, Yumirle P.; Wang, Kasper S.; Sherker, Averell H.; Sokol, Ronald J.; Bezerra, Jorge A.; Magee, John C.; Pediatrics, School of MedicineOBJECTIVE: 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 < .0001), weight (P = .009), and head circumference (P < .0001) with the largest impact noted for those with successful HPE. Growth trajectory for head circumference was significantly lower in patients treated with steroids irrespective of HPE status, but recovered during the second 6 months of life. 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.Item Presentation and Outcomes of Infants With Idiopathic Cholestasis: A Multicenter Prospective Study(Wolters Kluwer, 2021-10-01) Hertel, Paula M.; Hawthorne, Kieran; Kim, Sehee; Finegold, Milton J.; Shneider, Benjamin L.; Squires, James E.; Gupta, Nitika A.; Bull, Laura N.; Murray, Karen F.; Kerkar, Nanda; Ng, Vicky L.; Molleston, Jean P.; Bezerra, Jorge A.; Loomes, Kathleen M.; Taylor, Sarah A.; Schwarz, Kathleen B.; Turmelle, Yumirle P.; Rosenthal, Philip; Magee, John C.; Sokol, Ronald J.; Pediatrics, School of MedicineObjectives: The aim of the study was to determine the frequency and natural history of infantile idiopathic cholestasis (IC) in a large, prospective, multicenter cohort of infants. Methods: We studied 94 cholestatic infants enrolled up to 6 months of age in the NIDDK ChiLDReN (Childhood Liver Disease Research Network) "PROBE" protocol with a final diagnosis of IC; they were followed up to 30 months of age. Results: Male sex (66/94; 70%), preterm birth (22/90 with data; 24% born at < 37 weeks' gestational age), and low birth weight (25/89; 28% born at <2500 g) were frequent, with no significant differences between outcomes. Clinical outcomes included death (n = 1), liver transplant (n = 1), biochemical resolution (total bilirubin [TB] ≤1 mg/dL and ALT < 35 U/L; n = 51), partial resolution (TB > 1 mg/dL and/or ALT > 35 U/L; n = 7), and exited healthy (resolved disease per study site report but without documented biochemical resolution; n = 34). Biochemical resolution occurred at median of 9 months of age. GGT was <100 U/L at baseline in 34 of 83 participants (41%). Conclusions: Frequency of IC and of death or liver transplant was less common in this cohort than in previously published cohorts, likely because of recent discovery and diagnosis of genetic etiologies of severe/persistent cholestasis that previously were labeled as idiopathic. Preterm birth and other factors associated with increased vulnerability in neonates are relatively frequent and may contribute to IC. Overall outcome in IC is excellent. Low/normal GGT was common, possibly indicating a role for variants in genes associated with low-GGT cholestasis-this warrants further study.Item Risk of variceal hemorrhage and pretransplant mortality in children with biliary atresia(Wiley, 2022) Bass, Lee M.; Ye, Wen; Hawthorne, Kieran; Leung, Daniel H.; Murray, Karen F.; Molleston, Jean P.; Romero, Rene; Karpen, Saul; Rosenthal, Philip; Loomes, Kathleen M.; Wang, Kasper S.; Squires, Robert H.; Miethke, Alexander; Ng, Vicky L.; Horslen, Simon; Jensen, M. Kyle; Sokol, Ronald J.; Magee, John C.; Shneider, Benjamin L.; ChiLDReN; Pediatrics, School of MedicineBackground and aims: The natural history of gastroesophageal variceal hemorrhage (VH) in biliary atresia (BA) is not well characterized. We analyzed risk factors, incidence, and outcomes of VH in a longitudinal multicenter study. Approach and results: Participants enrolled in either an incident (Prospective Database of Infants with Cholestasis [PROBE]) or prevalent (Biliary Atresia Study of Infants and Children [BASIC]) cohort of BA were included. Variceal hemorrhage (VH) was defined based on gastrointestinal bleeding in the presence of varices accompanied by endoscopic or nontransplant surgical intervention. Cumulative incidence of VH and transplant-free survival was compared based on features of portal hypertension (e.g., splenomegaly, thrombocytopenia) and clinical parameters at baseline in each cohort (PROBE: 1.5 to 4.5 months after hepatoportoenterostomy [HPE]; BASIC: at enrollment > 3 years of age). Analyses were conducted on 869 children with BA enrolled between June 2004 and December 2020 (521 in PROBE [262 (51%) with a functioning HPE] and 348 in BASIC). The overall incidence of first observed VH at 5 years was 9.4% (95% CI: 7.0-12.4) in PROBE and 8.0% (5.2-11.5) in BASIC. Features of portal hypertension, platelet count, total bilirubin, aspartate aminotransferase (AST), albumin, and AST-to-platelet ratio index at baseline were associated with an increased risk of subsequent VH in both cohorts. Transplant-free survival at 5 years was 45.1% (40.5-49.6) in PROBE and 79.2% (74.1-83.4) in BASIC. Two (2.5%) of 80 participants who had VH died, whereas 10 (12.5%) underwent transplant within 6 weeks of VH. Conclusions: The low risk of VH and associated mortality in children with BA needs to be considered in decisions related to screening for varices and primary prophylaxis of VH.Item Serum bile acids as a prognostic biomarker in biliary atresia following Kasai portoenterostomy(Wolters Kluwer, 2023) Harpavat, Sanjiv; Hawthorne, Kieran; Setchell, Kenneth D. R.; Narvaez Rivas, Monica; Henn, Lisa; Beil, Charlotte A.; Karpen, Saul J.; Ng, Vicky L.; Alonso, Estella M.; Bezerra, Jorge A.; Guthery, Stephen L.; Horslen, Simon; Loomes, Kathy M.; McKiernan, Patrick; Magee, John C.; Merion, Robert M.; Molleston, Jean P.; Rosenthal, Philip; Thompson, Richard J.; Wang, Kasper S.; Sokol, Ronald J.; Shneider, Benjamin L.; Childhood Liver Disease Research Network (ChiLDReN); Pediatrics, School of MedicineBackground and aims: In biliary atresia, serum bilirubin is commonly used to predict outcomes after Kasai portoenterostomy (KP). Infants with persistently high levels invariably need liver transplant, but those achieving normalized levels have a less certain disease course. We hypothesized that serum bile acid levels could help predict outcomes in the latter group. Approach and results: Participants with biliary atresia from the Childhood Liver Disease Research Network were included if they had normalized bilirubin levels 6 months after KP and stored serum samples from the 6-month post-KP clinic visit ( n = 137). Bile acids were measured from the stored serum samples and used to divide participants into ≤40 μmol/L ( n = 43) or >40 μmol/L ( n = 94) groups. At 2 years of age, the ≤40 μmol/L compared with >40 μmol/L group had significantly lower total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, bile acids, and spleen size, as well as significantly higher albumin and platelet counts. Furthermore, during 734 person-years of follow-up, those in the ≤40 μmol/L group were significantly less likely to develop splenomegaly, ascites, gastrointestinal bleeding, or clinically evident portal hypertension. The ≤40 μmol/L group had a 10-year cumulative incidence of liver transplant/death of 8.5% (95% CI: 1.1%-26.1%), compared with 42.9% (95% CI: 28.6%-56.4%) for the >40 μmol/L group ( p = 0.001). Conclusions: Serum bile acid levels may be a useful prognostic biomarker for infants achieving normalized bilirubin levels after KP.