Alagille综合征的临床及病理特征分析

Clinical and histological characteristics of patients with Alagille syndrome

目的分析Alagille综合征(Alagille syndrome,ALGS)患者的临床特征、实验室指标、肝脏组织学、基因突变结果及预后特点。方法回顾性分析2016年1月至2022年2月于首都医科大学附属北京友谊医院明确诊断为ALGS患者27例,收集患者临床特征、实验室指标、病理组织学、基因测序结果。结果临床特征分析,生长发育迟缓16例(59.3%)、ALGS特殊面容8例(29.6%)、心血管受累16例(59.3%),蝴蝶椎骨10例(37.0%);肾脏受累8例(29.6%),角膜后胚胎环1例(3.7%);所有患者均有胆汁淤积,脾大23例(85.2%),食管胃底静脉曲张8例(29.6%),腹腔积液10例(37.0%),肝脏占位3例(11.1%)。病理特点分析,胆管消失16例(84.2%),汇管区炎症16例(84.2%),界面炎6例(31.6%),细胆管反应6例(31.6%),胆汁淤积12例(63.2%),胆盐淤积5例(26.3%);所有患者均存在不同程度的肝纤维化,其中肝硬化8例(42.1%)。基因检测分析,所有患者均为JAG1基因突变,其中1例合并NOTCH2基因突变,15例(68.2%)为自发突变。结论除特征性的多脏器受累及胆汁淤积表现外,应重视门脉高压及其并发症在ALGS病程进展中的地位;低月龄儿童的肝脏组织学可缺乏胆管消失综合征表现,应综合临床及肝脏组织学的其他特点进行分析。

Objective To find out the clinical characteristics and histological features of patients with Alagille syndrome(ALGS).Methods A total of 27 patients diagnosed with ALGS in Beijing Friendship Hospital from January 2016 to February 2022 were retrospectively enrolled.The demographic characteristics,clinical presentation,liver biochemical tests,gene sequencing,liver histology,and clinical outcomes of the patients were analyzed.Results The common clinical features were growth retardation(16/27,59.3%),facial features(8/27,29.6%),cardiovascular involvement(16/27,59.3%),butterfly vertebrae(10/27,37.0%),renal involvement(8/27,29.6%)and posterior embryonic(1,3.7%).All the cases were accompanied by chronic cholestasis,among which 23(85.2%)cases had splenomegaly.In addition,there were 8 cases(29.6%)of esophageal and gastric varices,10 cases(37.0%)of ascites,and 3 cases(11.1%)of hepatic lesions.The histological characteristics included ductopenia(16/27,84.2%),portal inflammation(16/27,84,2%),interface hepatitis(6/27,31.6%),ductular reaction(6/27,31.6%),cholestasis(12/27,63.2%)and cholate stasis(5/27,26.3%).All patients had different degrees of fibrosis.Among them,eight patients suffered from liver cirrhosis(42.1%).Gene sequencing showed that all patients had the JAG1 gene variant.There were 15 cases(68.2%)with spontaneous variants and one with the NOTCH2 gene variant.Conclusion In addition to the characteristic multiple organ involvement and cholestasis,attention should be paid to the role of portal hypertension and its complications in the progression of ALGS;Clinical symptoms combined with histological characteristics should be considered in infants due to the lack of the manifestation of ductopenia.