进行性家族性肝内胆汁淤积症的治疗进展

Progress in the treatment of progressive familial intrahepatic cholestasis

进行性家族性肝内胆汁淤积症(PFIC)是引起儿童期肝病死亡或移植的重要原因。目前在线人类孟德尔遗传(OMIM)数据库已收录12型PFIC,拓展了PFIC的疾病谱。PFIC目前的分型排名无明显规律,且部分PFIC的分型命名历经变迁。因此,业内专家建议采用相应突变基因/蛋白缺陷来命名此类疾病以避免混淆。基因型-表型关系的明确和/或表型预测因素的确立对改进PFIC患者的管理具有重要意义。2021年,肠道上皮细胞顶膜钠离子依赖性胆汁酸转运体抑制剂,奥维昔巴特(odevixibat)和氯马昔巴特(maralixibat)分别被欧洲国家和美国批准用于PFIC瘙痒症的治疗,增加了PFIC的治疗手段。此外,针对特定突变类型的个体化治疗和部分新的基因治疗手段正逐步走向临床,显示了良好的应用前景。

Progressive familial intrahepatic cholestasis(PFIC)is an important cause of liver-related death or transplantation in children.The PFIC spectrum is expanding,twelve types of PFIC are currently included in the Online Mendelian Inheritance in Man(OMIM)database.With the increase of PFIC types and the inconsistence of certain types in numbering,the current numbering classification of PFIC is confusing,so the experts in the field recommend using the corresponding mutant gene/protein defect to name different type of PFIC except for PFIC type 1-3.The clarification of the genotype-phenotype relationship and/or the establishment of phenotypic predictors significantly improved the management of patients with PFIC.Odevixibat and maralixibat,inhibitors of the apical sodium ion-dependent bile acid transporter on the intestinal epithelial cells,were approved in European Union and the United States for the treatment of PFIC pruritus in 2021,expanding the treatment options for PFIC.Additionally,personalized treatments for specific mutations and novel gene therapy is promising.