Sutton Harry, Sokol Ronald J, Kamath Binita M
Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Department of Pediatrics, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.
Hepatology. 2024 Jul 25. doi: 10.1097/HEP.0000000000001032.
Historically, the therapeutic options available to hepatologists managing cholestasis have been limited. Apart from bile acid--binding resins and the choleretic ursodeoxycholic acid, the medical management of cholestasis in children has been predominately focused on managing the complications of cholestasis, namely pruritus, malnutrition, fat-soluble vitamin deficiencies, and portal hypertension. As such, invasive surgical procedures such as biliary diversion and liver transplantation may become the only options for progressive and unremitting cases of cholestasis. Particularly in the pediatric population, where debilitating pruritus is a common indication for a liver transplant, effective anti-cholestatic medications have the potential to prolong native liver survival without the need for biliary diversion. Ileal bile acid transporter (IBAT) inhibitors are a relatively new class of drugs which that target the ileal re-uptake of bile acids, thus interrupting the enterohepatic circulation and reducing the total bile acid pool size and exposure of the liver. Oral, minimally absorbed IBAT inhibitors have been demonstrated to reduce serum bile acid levels and pruritus with a minimal side effect profile in clinical trials in Alagille Ssyndrome and progressive familial intrahepatic cholestasis, leading to FDA and EMA approval. The indications for IBAT inhibitors will likely expand in the coming years as clinical trials in other adult and pediatric cholestatic conditions are ongoing. This review will summarize the published clinical and pre-clinical data on IBAT inhibitors and offer providers guidance on their practical use.
从历史上看，肝病专家治疗胆汁淤积的可用治疗选择一直有限。除了胆汁酸结合树脂和利胆的熊去氧胆酸外，儿童胆汁淤积的药物治疗主要集中在处理胆汁淤积的并发症，即瘙痒、营养不良、脂溶性维生素缺乏和门静脉高压。因此，诸如胆汁分流术和肝移植等侵入性外科手术可能成为进展性和持续性胆汁淤积病例的唯一选择。特别是在儿科人群中，严重瘙痒是肝移植的常见指征，有效的抗胆汁淤积药物有可能延长自体肝脏存活时间，而无需进行胆汁分流。回肠胆汁酸转运体（IBAT）抑制剂是一类相对较新的药物，其作用靶点是胆汁酸的回肠重吸收，从而中断肠肝循环，减少总胆汁酸池大小和肝脏的暴露量。在阿拉吉耶综合征和进行性家族性肝内胆汁淤积的临床试验中，口服、极少吸收的IBAT抑制剂已被证明可降低血清胆汁酸水平和瘙痒，且副作用最小，从而获得了美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）的批准。随着针对其他成人和儿科胆汁淤积病症的临床试验正在进行，未来几年IBAT抑制剂的适应证可能会扩大。本综述将总结已发表的关于IBAT抑制剂的临床和临床前数据，并为医疗服务提供者提供其实际应用的指导。
