Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
Semin Liver Dis. 2018 Nov;38(4):299-307. doi: 10.1055/s-0038-1667299. Epub 2018 Oct 24.
ATP-binding cassette subfamily B member 4 (ABCB4) is a phospholipid translocator at the canalicular membrane of the hepatocyte, which "flops" phosphatidylcholine into bile. Dysfunction of this transporter due to gene variants can cause liver diseases and has been called ABCB4 deficiency. Several diseases including progressive familial intrahepatic cholestasis type 3 (PFIC3), low phospholipid-associated cholelithiasis (LPAC), a subgroup of patients developing intrahepatic cholestasis of pregnancy (ICP), drug-induced liver injury and chronic cholangiopathy with biliary fibrosis and cirrhosis were attributed to ABCB4 deficiency and characterized in the past decade. LPAC and ICP are usually caused by monoallelic variants, whereas patients affected by PFIC3 are homozygous or compound heterozygous carriers of variants. Treatment with ursodeoxycholic acid is often effective, but as the more severe forms of ABCB4 deficiency progress, nevertheless, new diagnostic and therapeutic approaches are warranted. Current functional classifications for ABCB4 deficiency-associated mutations can guide the development of novel genotype-based targeted pharmacotherapies for these conditions. Recently, increasing evidence from genome-wide association studies is emerging on associations of variants with hepatobiliary malignancies.
三磷酸腺苷结合盒亚家族 B 成员 4（ABCB4）是位于肝细胞胆小管膜的一种磷脂转运体，可将磷脂酰胆碱“翻转”入胆汁。由于基因突变导致该转运体功能异常可引起肝脏疾病，并被称为 ABCB4 缺乏症。过去十年中，已将几种疾病归因于 ABCB4 缺乏症并进行了特征描述，包括进行性家族性肝内胆汁淤积症 3 型（PFIC3）、低磷脂相关胆石症（LPAC）、妊娠肝内胆汁淤积症（ICP）的亚组患者、药物性肝损伤和伴有胆管纤维化和肝硬化的慢性胆管病。LPAC 和 ICP 通常由单等位基因突变引起，而受 PFIC3 影响的患者是 ABCB4 变异的纯合子或复合杂合子携带者。熊去氧胆酸治疗通常有效，但随着 ABCB4 缺乏症更严重形式的进展，仍需要新的诊断和治疗方法。目前针对 ABCB4 缺乏相关突变的功能分类可指导这些疾病基于基因型的新型靶向药物治疗的发展。最近，全基因组关联研究的越来越多证据表明与肝胆恶性肿瘤的 变异存在关联。
