Early life predictive markers of liver disease outcome in an International, Multicentre Cohort of children with Alagille syndrome.
Early life predictive markers of liver disease outcome in an International, Multicentre Cohort of children with Alagille syndrome.
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DOI：
10.1111/liv.12920
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
Kamath BM
中科院分区：
文献类型：
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作者：
Mouzaki M;Bass LM;Sokol RJ;Piccoli DA;Quammie C;Loomes KM;Heubi JE;Hertel PM;Scheenstra R;Furuya K;Kutsch E;Spinner NB;Robbins KN;Venkat V;Rosenthal P;Beyene J;Baker A;Kamath BM
Liver disease in Alagille syndrome is highly variable. Many of these 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, multicenter study was aimed at identifying early life predictors of liver disease outcome. 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. Sixty-seven had mild and 77 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 (65mmol/L) in that age-frame that differentiated between outcomes. A multivariable logistic regression model was developed using fibrosis, xanthomata and the total bilirubin cutoff of 3.8 mg/dL (65mmol/L), which generated an area under the ROC of 0.792. 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 presence of xanthomata on physical examination.
