Alam S, Lal BB. Recent updates on progressive familial intrahepatic cholestasis types 1, 2 and 3: Outcome and therapeutic strategies. World J Hepatol 2022; 14(1): 98-118 [PMID: 35126842 DOI: 10.4254/wjh.v14.i1.98]
Corresponding Author of This Article
Seema Alam, MD, Professor, Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi 110070, India. seema_alam@hotmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Jan 27, 2022; 14(1): 98-118 Published online Jan 27, 2022. doi: 10.4254/wjh.v14.i1.98
Recent updates on progressive familial intrahepatic cholestasis types 1, 2 and 3: Outcome and therapeutic strategies
Seema Alam, Bikrant Bihari Lal
Seema Alam, Bikrant Bihari Lal, Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi 110070, India
Author contributions: Alam S contributed to the conceptualization and intellectual input of final draft of manuscript; Lal BB contributed to the primary draft of manuscript, data collection and literature retrieval; and both authors contributed equally to the manuscript.
Conflict-of-interest statement: Seema Alam and Bikrant Bihari Lal declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Seema Alam, MD, Professor, Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi 110070, India. seema_alam@hotmail.com
Received: May 22, 2021 Peer-review started: May 22, 2021 First decision: July 6, 2021 Revised: July 17, 2021 Accepted: November 30, 2022 Article in press: November 30, 2021 Published online: January 27, 2022 Processing time: 243 Days and 21.5 Hours
Abstract
Recent evidence points towards the role of genotype to understand the phenotype, predict the natural course and long term outcome of patients with progressive familial intrahepatic cholestasis (PFIC). Expanded role of the heterozygous transporter defects presenting late needs to be suspected and identified. Treatment of pruritus, nutritional rehabilitation, prevention of fibrosis progression and liver transplantation (LT) in those with end stage liver disease form the crux of the treatment. LT in PFIC has its own unique issues like high rates of intractable diarrhoea, growth failure; steatohepatitis and graft failure in PFIC1 and antibody-mediated bile salt export pump deficiency in PFIC2. Drugs inhibiting apical sodium-dependent bile transporter and adenovirus-associated vector mediated gene therapy hold promise for future.
Core Tip: The spectrum of clinical manifestations in progressive familial intrahepatic cholestasis varies from mild to severe leading to end stage liver disease necessitating liver transplantation. Medical therapy forms the mainstay of treatment of pruritus with surgical biliary diversion reserved for refractory cases. Apical sodium bile salt co-transporter inhibitors are among the most promising newer drugs. This article describes the recent advances in understanding the clinical course and emerging therapies.
