Srivastava Anshu
Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh 226014, India.
J Clin Exp Hepatol. 2014 Mar;4(1):25-36. doi: 10.1016/j.jceh.2013.10.005. Epub 2013 Nov 23.
Progressive familial intrahepatic cholestasis (PFIC) is a group of rare disorders which are caused by defect in bile secretion and present with intrahepatic cholestasis, usually in infancy and childhood. These are autosomal recessive in inheritance. The estimated incidence is about 1 per 50,000 to 1 per 100,000 births, although exact prevalence is not known. These diseases affect both the genders equally and have been reported from all geographical areas. Based on clinical presentation, laboratory findings, liver histology and genetic defect, these are broadly divided into three types-PFIC type 1, PFIC type 2 and PFIC type 3. The defect is in ATP8B1 gene encoding the FIC1 protein, ABCB 11 gene encoding BSEP protein and ABCB4 gene encoding MDR3 protein in PFIC1, 2 and 3 respectively. The basic defect is impaired bile salt secretion in PFIC1/2 whereas in PFIC3, it is reduced biliary phospholipid secretion. The main clinical presentation is in the form of cholestatic jaundice and pruritus. Serum gamma glutamyl transpeptidase (GGT) is normal in patients with PFIC1/2 while it is raised in patients with PFIC3. Treatment includes nutritional support (adequate calories, supplementation of fat soluble vitamins and medium chain triglycerides) and use of medications to relieve pruritus as initial therapy followed by biliary diversion procedures in selected patients. Ultimately liver transplantation is needed in most patients as they develop progressive liver fibrosis, cirrhosis and end stage liver disease. Due to the high risk of developing liver tumors in PFIC2 patients, monitoring is recommended from infancy. Mutation targeted pharmacotherapy, gene therapy and hepatocyte transplantation are being explored as future therapeutic options.
进行性家族性肝内胆汁淤积症(PFIC)是一组罕见的疾病,由胆汁分泌缺陷引起,通常在婴儿期和儿童期出现肝内胆汁淤积。这些疾病为常染色体隐性遗传。估计发病率约为每50000至100000例出生中有1例,尽管确切患病率尚不清楚。这些疾病对男女影响相同,世界各地均有报道。根据临床表现、实验室检查结果、肝脏组织学和基因缺陷,这些疾病大致分为三种类型——PFIC 1型、PFIC 2型和PFIC 3型。PFIC 1型、2型和3型的缺陷分别在于编码FIC1蛋白的ATP8B1基因、编码BSEP蛋白的ABCB 11基因和编码MDR3蛋白的ABCB4基因。基本缺陷是PFIC 1/2型胆汁盐分泌受损,而PFIC 3型是胆汁磷脂分泌减少。主要临床表现为胆汁淤积性黄疸和瘙痒。PFIC 1/2型患者血清γ-谷氨酰转肽酶(GGT)正常,而PFIC 3型患者血清γ-谷氨酰转肽酶升高。治疗包括营养支持(充足的热量、补充脂溶性维生素和中链甘油三酯),并使用药物缓解瘙痒作为初始治疗,随后对选定患者进行胆汁转流手术。最终,大多数患者由于发展为进行性肝纤维化、肝硬化和终末期肝病而需要进行肝移植。由于PFIC 2型患者发生肝肿瘤的风险较高,建议从婴儿期开始进行监测。突变靶向药物治疗、基因治疗和肝细胞移植正在作为未来的治疗选择进行探索。
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