Carriers of ABCB4 gene variants show a mild clinical course, but impaired quality of life and limited risk for cholangiocarcinoma
Carriers of ABCB4 gene variants show a mild clinical course, but impaired quality of life and limited risk for cholangiocarcinoma
复制标题
DOI：
10.1111/liv.14662
复制
发表时间：
2020-12-01
影响因子：
6.7
通讯作者：
Beuers, Ulrich
中科院分区：
文献类型：
--
作者：
de Vries, Elsemieke;Mazzetti, Marta;Beuers, Ulrich
背景与目的三磷酸腺苷结合盒B亚家族成员4(ABCB4)缺乏可导致进行性家族性肝内胆汁淤积症(PFIC3)、胆汁性肝硬变、低磷脂相关性胆石症(LPAC)、妊娠肝内胆汁淤积症(ICP)、口服避孕药诱导性胆汁淤积症(CIC)或无症状。对ABCB4缺乏症患者的长期病程、生活质量和组织学进行调查。方法对两个地区学术中心ABCB4基因变异的成人携带者进行病史记录、电子病历、体格检查、血液分析、腹部超声(US)和肝脏弹性成像分析。患者完成了生活质量的36项简短健康调查(SF-36)和瘙痒的视觉模拟量表(VAS)。现有的肝脏标本根据Nakanuma评分系统进行了重新分类，到目前为止，仅验证了原发性胆管炎(PBC)和原发性硬化性胆管炎(PSC)。结果共确诊67例患者，分析时(96%)仍健在，62例(93%)曾接受熊去氧胆酸治疗。两名患者死于胆管癌(CCA)，一名患者死于失代偿性胆汁性肝硬化。据报道，在一级亲属中又有三例CCA死亡。无移植存活率为91%(中位随访14年)。肝脏硬度正常(
Background and Aims Adenosine triphosphate-binding cassette subfamily B member 4 (ABCB4) deficiency may lead to progressive familial intrahepatic cholestasis type 3 (PFIC3), biliary cirrhosis, low phospholipid-associated cholelithiasis (LPAC), intrahepatic cholestasis of pregnancy (ICP), oral contraceptive-induced cholestasis (CIC) or may remain asymptomatic. The long-term course, quality of life and histology were investigated in ABCB4 deficiency.Methods Adult carriers of ABCB4 gene variants from two regional academic centres were analysed by history taking, electronic patient files, physical examination, blood analysis, abdominal ultrasound (US) and liver elastography. Patients completed a 36-Item Short Form Health Survey (SF-36) for quality of life and a Visual Analogue Scale (VAS) for pruritus. Available liver specimens were re-classified according to the Nakanuma scoring system, so far validated for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) only. Quality of life data were compared to published data of patients with PBC, PSC and the general population.Results Sixty-seven patients were identified, 64 (96%) were alive at the time of analysis and 62 (93%) were (at some time) treated with ursodeoxycholic acid (UDCA). Two patients died of cholangiocarcinoma (CCA), and one of decompensated biliary cirrhosis. Three additional deaths of CCA were reported in first-degree relatives. Transplant-free survival was 91% (median follow-up 14 years). Liver stiffness was normal (