Paediatric Liver Centre, King's College Hospital, London, UK.
Division of Gastroenterology, Hepatology and Nutrition, Golisano Children's Hospital, University of Rochester Medical Center, Rochester, NY, USA.
Clin Res Hepatol Gastroenterol. 2019 Feb;43(1):20-36. doi: 10.1016/j.clinre.2018.07.010. Epub 2018 Sep 17.
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of rare genetic disorders associated with bile acid secretion or transport defects. This is the first systematic review of the epidemiology, natural history and burden of PFIC.
MEDLINE and Embase were searched for publications on PFIC prevalence, incidence or natural history, and the economic burden or health-related quality of life (HRQoL) of patients with PFIC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
Of 1269 records screened, 20 were eligible (epidemiology, 17; humanistic burden, 5; both, 2). Incidence of intrahepatic cholestasis, including but not limited to PFIC, was 1/18 000 live births in one study that did not use genetic testing. In two studies of infants and children (2-18 years) with cholestasis, 12-13% had genetically diagnosed PFIC. Of the three main PFIC subtypes, PFIC2 was the most common (21-91% of patients). Common symptoms (e.g. pruritus, jaundice, hepatomegaly, splenomegaly) generally appeared at about 3 months of age and tended to emerge earliest in patients with PFIC2. Patients reported that pruritus was often severe and led to dermal damage and reduced HRQoL. Disease progression led to complications including liver failure and hepatocellular carcinoma, with 20-83% of patients requiring liver transplantation. Mortality was 0-87% across 10 studies (treatment varied among studies), with a median age at death of ~4 years in one study.
Patients with PFIC face debilitating symptoms and poor prognosis. Further research is needed to inform patient management and clinical trial design. Published data on the epidemiology and socioeconomic burden of PFIC is limited.
进行性家族性肝内胆汁淤积症（PFIC）是一组罕见的遗传性疾病，与胆汁酸分泌或转运缺陷有关。这是对 PFIC 的流行病学、自然史和负担进行的首次系统评价。
检索 MEDLINE 和 Embase 上关于 PFIC 患病率、发病率或自然史的文献，以及 PFIC 患者的经济负担或健康相关生活质量（HRQoL）的文献。遵循系统评价和荟萃分析的首选报告项目指南。
在筛选的 1269 条记录中，有 20 条符合条件（流行病学 17 条；人文负担 5 条；两者均有 2 条）。一项未进行基因检测的研究表明，包括但不限于 PFIC 的肝内胆汁淤积症的发病率为每 18000 例活产婴儿 1 例。在两项针对患有胆汁淤积症的婴儿和儿童（2-18 岁）的研究中，有 12-13%的患儿被基因诊断为 PFIC。在三种主要的 PFIC 亚型中，PFIC2 最常见（21-91%的患者）。常见症状（如瘙痒、黄疸、肝肿大、脾肿大）通常在 3 个月左右出现，且在 PFIC2 患者中最早出现。患者报告说瘙痒通常很严重，导致皮肤损伤和 HRQoL 降低。疾病进展导致并发症，包括肝功能衰竭和肝细胞癌，20-83%的患者需要进行肝移植。在 10 项研究中（治疗方法因研究而异），死亡率为 0-87%，在一项研究中，死亡的中位年龄约为 4 岁。
PFIC 患者面临严重的症状和不良预后。需要进一步研究以指导患者管理和临床试验设计。关于 PFIC 的流行病学和社会经济负担的已发表数据有限。
