Abstract：
UNASSIGNED: Progressive familial intrahepatic cholestasis (PFIC) is a group of disorders characterized by inappropriate bile formation, causing hepatic accumulation of bile acids and, subsequently, liver injury. Until recently, no approved treatments were available for these patients.
UNASSIGNED: Recent clinical trials for PFIC treatment have focused on intestine-restricted ileal bile acid transporter (IBAT) inhibitors. These compounds aim to reduce the pool size of bile acids by interrupting their enterohepatic circulation. Other emerging treatments in the pipeline include systemic IBAT inhibitors, synthetic bile acid derivatives, compounds targeting bile acid synthesis via the FXR/FGF axis, and chaperones/potentiators that aim to enhance the residual activity of the mutated transporters.
UNASSIGNED: Substantial progress has been made in drug development for PFIC patients during the last couple of years. Although data concerning long-term efficacy are as yet only scarcely available, new therapies have demonstrated robust efficacy in a considerable fraction of patients at least on the shorter term. However, a substantial fraction of PFIC patients do not respond to these novel therapies and thus still requires surgical treatment, including liver transplantation before adulthood. Hence, there is still an unmet medical need for long-term effective medical, preferably non-surgical, treatment for all PFIC patients.
Normally, the liver produces bile which is a route of secretion of waste products from the body and also helps in the intestinal absorption of fats from the diet. The bile goes from the liver, through the bile duct to the intestines and components are taken up again at the end of the intestine and transported back to the liver. However, progressive familial intrahepatic cholestasis (PFIC in short) is a group of diseases where bile stays in the liver and damages it. PFIC often causes symptoms already in very young children, like itch and jaundice (getting a slight yellow color). Patients get more and worse symptoms over time and may eventually need a liver transplantation. This review discusses what drugs have been developed for PFIC recently and what drugs are in development now. Two new drugs for PFIC have been developed and approved in the last few years: odevixibat and maralixibat. These drugs help bile in the intestines leave the body via the stool and prevent bile from going back to the liver instead. Drugs in development aim to either 1) do the same, 2) make the bile less toxic, 3) reduce the production of bile, or 4) help bile go from the liver into the bile ducts. There has been a lot of progress in drug development for PFIC in the last few years. The new drugs have helped a considerable number of patients, but many patients still do not respond to these new drugs, keep having symptoms and may need surgery. Therefore, despite considerable progress, research needs to continue for an effective treatment for all PFIC patients.
UNASSIGNED: Recent clinical trials for PFIC treatment have focused on intestine-restricted ileal bile acid transporter (IBAT) inhibitors. These compounds aim to reduce the pool size of bile acids by interrupting their enterohepatic circulation. Other emerging treatments in the pipeline include systemic IBAT inhibitors, synthetic bile acid derivatives, compounds targeting bile acid synthesis via the FXR/FGF axis, and chaperones/potentiators that aim to enhance the residual activity of the mutated transporters.
UNASSIGNED: Substantial progress has been made in drug development for PFIC patients during the last couple of years. Although data concerning long-term efficacy are as yet only scarcely available, new therapies have demonstrated robust efficacy in a considerable fraction of patients at least on the shorter term. However, a substantial fraction of PFIC patients do not respond to these novel therapies and thus still requires surgical treatment, including liver transplantation before adulthood. Hence, there is still an unmet medical need for long-term effective medical, preferably non-surgical, treatment for all PFIC patients.
Normally, the liver produces bile which is a route of secretion of waste products from the body and also helps in the intestinal absorption of fats from the diet. The bile goes from the liver, through the bile duct to the intestines and components are taken up again at the end of the intestine and transported back to the liver. However, progressive familial intrahepatic cholestasis (PFIC in short) is a group of diseases where bile stays in the liver and damages it. PFIC often causes symptoms already in very young children, like itch and jaundice (getting a slight yellow color). Patients get more and worse symptoms over time and may eventually need a liver transplantation. This review discusses what drugs have been developed for PFIC recently and what drugs are in development now. Two new drugs for PFIC have been developed and approved in the last few years: odevixibat and maralixibat. These drugs help bile in the intestines leave the body via the stool and prevent bile from going back to the liver instead. Drugs in development aim to either 1) do the same, 2) make the bile less toxic, 3) reduce the production of bile, or 4) help bile go from the liver into the bile ducts. There has been a lot of progress in drug development for PFIC in the last few years. The new drugs have helped a considerable number of patients, but many patients still do not respond to these new drugs, keep having symptoms and may need surgery. Therefore, despite considerable progress, research needs to continue for an effective treatment for all PFIC patients.
摘要：
■进行性家族性肝内胆汁淤积症（PFIC）是一组以胆汁形成不当为特征的疾病，引起胆汁酸的肝脏积累，随后,肝损伤。直到最近,这些患者没有获得批准的治疗.
■最近PFIC治疗的临床试验集中在肠限制回肠胆汁酸转运蛋白（IBAT）抑制剂上。这些化合物旨在通过中断胆汁酸的肝肠循环来减少胆汁酸的池大小。管道中的其他新兴治疗方法包括全身性IBAT抑制剂，合成胆汁酸衍生物，通过FXR/FGF轴靶向胆汁酸合成的化合物，和旨在增强突变转运蛋白的残留活性的伴侣/增效剂。
■在过去几年中，PFIC患者的药物开发取得了实质性进展。尽管有关长期疗效的数据目前几乎没有，新疗法已在相当一部分患者中显示出稳健的疗效,至少在短期内如此.然而,大部分PFIC患者对这些新疗法没有反应，因此仍然需要手术治疗，包括成年前的肝移植。因此，对于长期有效的医疗，仍然有一个未满足的医疗，最好是非手术，所有PFIC患者的治疗。
通常，肝脏产生胆汁，胆汁是人体分泌废物的途径，也有助于肠道从饮食中吸收脂肪。胆汁来自肝脏,通过胆管到达肠道，成分在肠道末端再次被吸收并运回肝脏。然而,进行性家族性肝内胆汁淤积症（简称PFIC）是一组胆汁停留在肝脏中并损害肝脏的疾病。PFIC经常在非常年幼的儿童中引起症状，像痒和黄疸（得到轻微的黄色）。随着时间的推移，患者的症状会越来越严重，最终可能需要肝移植。这篇综述讨论了最近为PFIC开发了哪些药物以及现在正在开发哪些药物。在过去的几年中，已经开发并批准了两种用于PFIC的新药：odevixibat和maralixibat。这些药物帮助肠道中的胆汁通过粪便离开身体，并防止胆汁返回肝脏。开发中的药物的目标是1)做同样的事情，2）使胆汁毒性更小，3）减少胆汁的产生，或4）帮助胆汁从肝脏进入胆管。在过去的几年中，PFIC的药物开发取得了很大进展。新药帮助了相当多的病人,但是许多患者仍然对这些新药没有反应，继续有症状，可能需要手术。因此,尽管取得了相当大的进展，研究需要继续为所有PFIC患者提供有效的治疗。
■最近PFIC治疗的临床试验集中在肠限制回肠胆汁酸转运蛋白（IBAT）抑制剂上。这些化合物旨在通过中断胆汁酸的肝肠循环来减少胆汁酸的池大小。管道中的其他新兴治疗方法包括全身性IBAT抑制剂，合成胆汁酸衍生物，通过FXR/FGF轴靶向胆汁酸合成的化合物，和旨在增强突变转运蛋白的残留活性的伴侣/增效剂。
■在过去几年中，PFIC患者的药物开发取得了实质性进展。尽管有关长期疗效的数据目前几乎没有，新疗法已在相当一部分患者中显示出稳健的疗效,至少在短期内如此.然而,大部分PFIC患者对这些新疗法没有反应，因此仍然需要手术治疗，包括成年前的肝移植。因此，对于长期有效的医疗，仍然有一个未满足的医疗，最好是非手术，所有PFIC患者的治疗。
通常，肝脏产生胆汁，胆汁是人体分泌废物的途径，也有助于肠道从饮食中吸收脂肪。胆汁来自肝脏,通过胆管到达肠道，成分在肠道末端再次被吸收并运回肝脏。然而,进行性家族性肝内胆汁淤积症（简称PFIC）是一组胆汁停留在肝脏中并损害肝脏的疾病。PFIC经常在非常年幼的儿童中引起症状，像痒和黄疸（得到轻微的黄色）。随着时间的推移，患者的症状会越来越严重，最终可能需要肝移植。这篇综述讨论了最近为PFIC开发了哪些药物以及现在正在开发哪些药物。在过去的几年中，已经开发并批准了两种用于PFIC的新药：odevixibat和maralixibat。这些药物帮助肠道中的胆汁通过粪便离开身体，并防止胆汁返回肝脏。开发中的药物的目标是1)做同样的事情，2）使胆汁毒性更小，3）减少胆汁的产生，或4）帮助胆汁从肝脏进入胆管。在过去的几年中，PFIC的药物开发取得了很大进展。新药帮助了相当多的病人,但是许多患者仍然对这些新药没有反应，继续有症状，可能需要手术。因此,尽管取得了相当大的进展，研究需要继续为所有PFIC患者提供有效的治疗。
