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
Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Canada.
Division of Gastroenterology, Hepatology and Nutrition, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
Liver Int. 2016 May;36(5):755-60. doi: 10.1111/liv.12920. Epub 2015 Aug 18.
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.
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 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.
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.
阿拉吉耶综合征中的肝脏疾病具有高度变异性。许多在生命早期出现严重胆汁淤积的患者会自发改善；然而，10% - 20%的患者会出现疾病进展。目前尚无法预测阿拉吉耶综合征的长期肝脏结局。这项国际多中心研究旨在确定肝脏疾病结局的早期预测因素。
收集了144例阿拉吉耶综合征患者的回顾性临床、实验室和影像学数据，这些患者的长期肝脏结局已根据先前发表的标准预先确定。
67例患者肝脏结局为轻度，77例为重度。单因素分析表明，两组之间活检时的胆汁淤积和纤维化以及黄瘤的存在有显著差异（均P < 0.05）。混合模型分析显示，血清总胆红素和血清胆固醇也与结局相关（分别为P = 0.001和P = 0.002）。数据的图形表示显示，轻度组在12至24个月龄之间总胆红素水平有变化。递归划分确定了该年龄范围内总胆红素的阈值为3.8 mg/dl（65 μmol/L），可区分不同结局。使用纤维化、黄瘤和总胆红素阈值3.8 mg/dl（65 μmol/L）建立了多变量逻辑回归模型，其ROC曲线下面积为0.792。
阿拉吉耶综合征患者的长期肝脏结局可根据12 - 24个月龄之间的血清总胆红素、肝脏活检的纤维化情况以及体格检查中黄瘤的存在来预测。
