Progressive familial intrahepatic cholestasis: From childhood to adulthood
World Journal of Gastroenterology, cilt.32, sa.41, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Derleme
- Cilt numarası: 32 Sayı: 41
- Basım Tarihi: 2026
- Doi Numarası: 10.3748/wjg.121544
- Dergi Adı: World Journal of Gastroenterology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE
- Anahtar Kelimeler: Bile acid transport, Cholestasis, Genotype-phenotype correlation, Ileal bile
- Hacettepe Üniversitesi Adresli: Evet
Özet
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.