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Early life predictive markers of liver disease outcome in an International, Multicentre Cohort of children with Alagille syndrome
Author(s) -
Mouzaki Marialena,
Bass Lee M.,
Sokol Ronald J.,
Piccoli David A.,
Quammie Claudia,
Loomes Kathleen M.,
Heubi James E.,
Hertel Paula M.,
Scheenstra Rene,
Furuya Katryn,
Kutsch Erika,
Spinner Nancy B.,
Robbins Kristen N.,
Venkat Veena,
Rosenthal Philip,
Beyene Joseph,
Baker Alastair,
Kamath Binita M.
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12920
Subject(s) - alagille syndrome , medicine , cholestasis , gastroenterology , liver biopsy , retrospective cohort study , cohort , liver disease , biliary atresia , bilirubin , univariate analysis , neonatal cholestasis , biopsy , liver transplantation , multivariate analysis , transplantation
Background & Aims Liver disease in Alagille syndrome is highly variable. Many of the patients presenting with severe cholestasis early in life improve spontaneously; 10–20%, however, have progressive disease. It is currently not possible to predict long‐term hepatic outcomes in Alagille syndrome. This international, multicentre study was aimed at identifying early life predictors of liver disease outcome. Methods Retrospective clinical, laboratory and radiographic data from a cohort of 144 Alagille syndrome patients, whose long‐term hepatic outcomes had been determined a priori based on previously published criteria, were collected. Results Sixty‐seven patients had mild and 77 had severe hepatic outcome. Univariate analysis demonstrated that cholestasis and fibrosis on biopsy, as well as the presence of xanthomata were significantly different between the groups ( P < 0.05 for all). Mixed model analysis revealed that total serum bilirubin and serum cholesterol were also associated with outcome ( P = 0.001 and P = 0.002, respectively). Graphical representation of the data revealed a change in total bilirubin levels between 12 and 24 months of age in the mild group. Recursive partitioning identified a threshold for total bilirubin of 3.8 mg/dl (65 mmol/L) in that age‐frame that differentiated between outcomes. A multivariable logistic regression model was developed using fibrosis, xanthomata and the total bilirubin cut‐off of 3.8 mg/dl (65 mmol/L), which generated an area under the ROC curve of 0.792. Conclusions The long‐term hepatic outcomes of patients with Alagille syndrome can be predicted based on serum total bilirubin between the ages of 12–24 months combined with fibrosis on liver biopsy and the presence of xanthomata on physical examination.