进行性家族性肝内胆汁淤积症

Progressive familial intrahepatic cholestasis

进行性家族性肝内胆汁淤积症(PFIC)是一组罕见的异质性常染色体隐性遗传病,涉及胆汁酸形成及分泌各个环节。依据其基因突变类型不同,分为PFIC 1-6型。随着基因诊断技术的发展,更多新的突变基因被鉴定出来,如ABCC12、VPS33B等,使诊断和治疗更加精准化。PFIC临床以进行性的黄疸和瘙痒、不同程度生长发育障碍、脂溶性维生素缺乏为特点。除PFIC3外,其他各型PFIC血清γ-谷氨酰转肽酶水平正常或大致正常,此点为临床诊断该病重要线索。但各型PFIC在发病年龄、病情轻重、肝外症状、预后等方面各有特点,随着病情的进展,最终发展为肝纤维化、肝硬化和肝功能衰竭。治疗包括营养、药物、非移植性手术治疗及肝移植。近年来转运体、基因治疗等的研究为PFIC患者带来了新的希望。

Progressive familial intrahepatic cholestasis(PFIC)is a rare heterogenous groups of autosomal recessive monogenic disease,resulting in abnormal bile acid formation and secretion.According to the type of gene mutation,PFIC was classified as PFIC 1-6 and more new mutated genes have been identified,such as ABCC12,VPS33B,et al,making diagnosis and treatment more accurate.PFIC is characterized by progressive jaundice and pruritus,growth and development disorders,and fat-soluble vitamin deficiency.Except for PFIC3,the level ofγ-glutamyl transpeptidase in serum of PFIC is normal,which is an important clue for clinical diagnosis.However,each type of PFIC has its own characteristics such as the age of onset,disease severity,extrahepatic symptoms,and prognosis.With the progress of the disease,it eventually develops into fibrosis,cirrhosis and liver failure.Treatment includes nutrition,medication,partial external/internal biliary diversion,and liver transplantation.Recent studies on transporters and gene therapy have brought new hope to patients with PFIC.