Genotypes and different clinical variants between children and adults in progressive familial intrahepatic cholestasis: a state-of-the-art review

Progressive familial intrahepatic cholestasis (PFIC) are rare, known paediatric-onset disorders of BA secretion and transport whose diagnosis is based on clinical symptoms to be confirmed with genetic tests that often reveal homozygosity or compound heterozygosity. Several adult-onset cholestasis share mutations in PFIC genes, usually as single heterozygosity, albeit presenting with different phenotypes compared to children-onset PFIC. Although adult-onset PFIC phenotypes generally progress less rapidly and are less severe, there is a significant risk of gallstones, intrahepatic cholestasis of pregnancy, drug-induced liver injury, fibrosis, cirrhosis, and liver malignancy. After the clinical observation of phenotypes attributable to PFIC, current research techniques enable the isolation of novel variants related to known genes or variants in other genes that determine known or new cholestatic intrahepatic phenotypes. In children with PFIC, new treatments based on BA transporter inhibitors allow for controlling the pruritus symptom and cholestasis, making native liver survival more likely. BAs transporter inhibitors are indicated in paediatric patients in PFIC phenotypes. The importance of early and accurate diagnosis is becoming crucial. There is a continuum in patient management, with paediatric to adult hepatologists collaborating with geneticists. Educational programs to ensure the recognition of PFIC genes in adult-onset cholestasis will be mandatory to transform the new knowledge into a broad improvement for the patients and their families.