Islek A, İşlek SK, Tumgor G. Progressive familial intrahepatic cholestasis: From childhood to adulthood. World J Gastroenterol 2026; 32(41): 121544 [DOI: 10.3748/wjg.121544]
Corresponding Author of This Article
Gokhan Tumgor, MD, Professor, Department of Pediatric Gastroenterology, Cukurova University School of Medicine, South Campus Street, Balcalı village, 15/10 Saricam, Adana 01330, Türkiye. gtumgor74@yahoo.com
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Gastroenterology & Hepatology
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Islek A, İşlek SK, Tumgor G. Progressive familial intrahepatic cholestasis: From childhood to adulthood. World J Gastroenterol 2026; 32(41): 121544 [DOI: 10.3748/wjg.121544]
World J Gastroenterol. Nov 7, 2026; 32(41): 121544 Published online Nov 7, 2026. doi: 10.3748/wjg.121544
Progressive familial intrahepatic cholestasis: From childhood to adulthood
Ali Islek, Serap Ketenci İşlek, Gokhan Tumgor
Ali Islek, Gokhan Tumgor, Department of Pediatric Gastroenterology, Cukurova University School of Medicine, Adana 01330, Türkiye
Serap Ketenci İşlek, Department of Pediatric Genetic, Hacettepe University School of Medicine, Ankara 06100, Türkiye
Author contributions: Islek A and Tumgor G contributed to the conception and design of the study, performed the literature review and drafted the manuscript; İşlek SK contributed to the genetic interpretation and provided critical input on molecular aspects of the study; Tumgor G contributed to clinical interpretation with a focus on pediatric gastroenterology and hepatology and critically revised the manuscript; all authors contributed to data interpretation, critically revised the manuscript for important intellectual content, and approved the final version of the manuscript.
AI contribution statement: ChatGPT, Grammarly, and DeepL were used for English spelling and grammar correction. AI was used only for English language correction. Figure 1 was created with the aid of artificial intelligence. All AI-generated images were reviewed, verified, and approved by the authors, who take full responsibility for the accuracy, originality, and integrity of the final content.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Gokhan Tumgor, MD, Professor, Department of Pediatric Gastroenterology, Cukurova University School of Medicine, South Campus Street, Balcalı village, 15/10 Saricam, Adana 01330, Türkiye. gtumgor74@yahoo.com
Received: March 27, 2026 Revised: May 25, 2026 Accepted: June 8, 2026 Published online: November 7, 2026 Processing time: 172 Days and 3.7 Hours
Abstract
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of inherited cholestatic liver disorders characterized by impaired bile formation and secretion. Although traditionally classified into numbered subtypes, PFIC is now increasingly understood within a mechanism-based framework involving defects in canalicular transport, membrane lipid homeostasis, tight junction integrity, intracellular trafficking, and bile acid regulatory pathways. This evolving classification better accounts for the marked phenotypic variability, overlapping clinical presentations, and expanding genetic spectrum of the disease. From a clinical perspective, PFIC typically presents with cholestasis, pruritus, and growth impairment in infancy or early childhood. However, accumulating evidence indicates that disease expression may extend into adolescence and adulthood, with milder or atypical phenotypes increasingly recognized. Biochemical stratification, particularly based on gamma-glutamyl transferase levels, remains a key diagnostic entry point, but genetic testing is required for definitive diagnosis. Genotype-phenotype correlations, especially in ABCB11- and ABCB4-related diseases, have important implications for prognosis and malignancy risk. Furthermore, recent advances in pathophysiology have informed the development of targeted therapies, including ileal bile acid transporter inhibitors, while surgical approaches and liver transplantation remain essential in advanced disease. This review provides a comprehensive overview of the molecular mechanisms, clinical features, diagnostic strategies, and current as well as emerging therapeutic approaches for PFIC.
Core Tip: Progressive familial intrahepatic cholestasis (PFIC) is a genetically and mechanistically diverse group of cholestatic liver disorders whose clinical spectrum spans from childhood well into adulthood. The disease classification has evolved from a numerical system to a mechanism-based framework encompassing defects in canalicular transport, membrane stability, tight junction integrity, intracellular trafficking, and bile acid regulation. This comprehensive review underscores the significance of integrating early genetic testing with biochemical patterns, particularly gamma-glutamyl transferase levels, for accurate diagnosis. Genotype-phenotype correlations and extrahepatic manifestations are essential for prognostic assessment and individualized management. Emerging targeted therapies, including ileal bile acid transporter inhibitors, support a mechanism-driven approach to PFIC.
