Abstract
PURPOSE: The aim of this study was to elucidate the genetic variants associated with progressive familial intrahepatic cholestasis (PFIC), a rare class of disorders driven by pathogenic monogenic variants in bile acid transporters. Furthermore, the long-term clinical outcomes of PFIC patients were evaluated. METHODS: A retrospective cohort study was conducted at Seoul National University Hospital and included pediatric patients diagnosed with PFIC and confirmed by genetic testing between January 2000 and October 2024. Genetic testing, encompassing either single-gene testing or a neonatal cholestasis 34-gene panel, was performed for all patients. RESULTS: Six patients were identified, including five with PFIC2, classified as bile salt export pump deficiency, and one with PFIC3, classified as multidrug resistance protein 3 deficiency. The median age of symptom onset was 3 months. The genetic analyses revealed no widely known variants associated with PFIC. However, a novel frameshift variant (c.589dup, p.(Glu197GlyfsTer8)) was detected in the ABCB11 gene. Additionally, a missense variant (c.3812T>A, p.(Ile1271Asn)) was commonly identified in the same gene. All patients ultimately underwent liver transplantation; two patients who developed hepatocellular carcinoma (HCC) were diagnosed at a median age of 1.6 years. Notably, all patients survived without recurrence after transplantation, with a median follow-up duration of 12.0 years. CONCLUSION: This study is the first documented case of PFIC3 in a Korean child. Genotype is not associated with the risk of developing HCC. Given the early diagnosis of HCC observed in some patients, routine surveillance for HCC is strongly recommended in all patients with PFIC2.