Congenital hepatic fibrosis and related ciliopathies across the life course: current management, disease burden, and unmet needs in the era of genomic diagnosis and translational therapeutics

Vollständiger Abstract

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Congenital hepatic fibrosis (CHF) is a rare autosomal recessive hepatobiliary developmental disorder characterised by extensive fibrosis of the portal tracts and ductal plate malformation, representing a significant cause of portal hypertension in children and adolescents. Despite its low incidence, the disease exhibits considerable clinical heterogeneity, ranging from asymptomatic presentations to severe complications of portal hypertension, thereby posing substantial diagnostic and management challenges. The long-term disease burden is profound, adversely affecting both quality of life and prognosis. Currently, clinical management focuses primarily on the surveillance and treatment of portal hypertensive complications, with a conspicuous absence of targeted therapies addressing the underlying disease processes. Furthermore, notable deficiencies persist in multidisciplinary coordination, individualised therapeutic strategies, and long-term follow-up frameworks. This review aims to comprehensively examine the pathophysiology, genetics, clinical manifestations, diagnostic approaches, complication management strategies, and therapeutic interventions pertaining to this condition. It systematically evaluates the associated disease burden and critically appraises the limitations of current diagnostic and treatment paradigms, as well as the unmet needs in clinical practice. Ultimately, this review seeks to provide critical insights and a theoretical framework to inform future research directions, optimise therapeutic regimens, and facilitate the development of integrated care models. Unlike previous reviews focusing mainly on pathology or case-based clinical presentation, this review emphasizes life-course management, patient burden, and translational gaps in the era of genomic diagnosis.