New hope in treating progressive familial intrahepatic cholestasis in children
Lama Ebrahim Mkarem1, Mohammed Ali Hosny Batika1, Rana Bitar2,3
1Department of Paediatrics, Sheikh Khalifa Medical City, Abu Dhabi 767451, United Arab Emirates.
Insights
Progressive familial intrahepatic cholestasis (PFIC) is a rare liver disease in children. Ileal bile acid transporter (IBAT) inhibitors offer a potential non-surgical treatment to reduce bile acid buildup and improve symptoms.
Area of Science:
- Hepatology
- Pediatric Gastroenterology
- Pharmacology
Background:
- Progressive familial intrahepatic cholestasis (PFIC) encompasses rare, inherited liver diseases in children characterized by impaired bile flow (cholestasis).
- PFIC leads to bile acid accumulation, liver inflammation, pruritus, and progressive liver damage, with historically limited treatment options beyond supportive care.
- Surgical biliary diversion has shown efficacy by interrupting bile acid enterohepatic circulation, improving liver function and quality of life.
Purpose of the Study:
- To present the 13 distinct types of Progressive familial intrahepatic cholestasis (PFIC).
- To review the current evidence regarding the efficacy of ileal bile acid transporter (IBAT) inhibitors in treating pediatric PFIC patients.
- To explore non-surgical therapeutic strategies for PFIC by targeting bile acid metabolism.
Main Methods:
- Literature review of existing studies on PFIC and IBAT inhibitors.
- Analysis of clinical trial data and case reports on the use of IBAT inhibitors in pediatric populations.
- Comparative assessment of surgical and non-surgical interventions for PFIC.
Main Results:
- IBAT inhibition demonstrates potential in reducing serum bile acids and alleviating pruritus in PFIC.
- Surgical biliary diversion has proven effective in normalizing bile acids, reducing liver injury, and enhancing patient quality of life.
- Evidence suggests IBAT inhibitors represent a promising non-surgical approach to interrupt bile acid enterohepatic circulation.
Conclusions:
- IBAT inhibitors offer a novel, non-surgical therapeutic avenue for managing PFIC by modulating bile acid circulation.
- Further research and clinical trials are warranted to establish the long-term efficacy and safety of IBAT inhibitors across different PFIC subtypes.
- Targeting the ileal bile acid transporter provides a promising strategy to improve outcomes for children with PFIC.
Abstract:
Progressive familial intrahepatic cholestasis (PFIC) is a group of rare, inherited cholestatic liver disorders presenting in infants and children and are associated with impaired bile flow (i.e., cholestasis), pruritus and progressive liver disease. Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive. The impaired bile flow within the liver, leads to accumulation in the liver and inflammation. Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive. A potential for reducing pathologic bile accumulation in the liver is surgical biliary diversion, with an aim to interrupt the enterohepatic circulation. These procedures have demonstrated a positive effect in PFIC by normalizing serum bile acids, reducing pruritus and liver injury and improving the patient quality of life. Nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter (IBAT). IBAT inhibition has demonstrated efficacy in reducing serum bile acids and pruritus. We aim to present the 13 types of PFIC and the current evidence on the use of IBAT inhibitors in treating children with PFIC.
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