The disease burden and health-related quality of life in Chinese children with genetic cholestatic liver diseases: a cross-sectional study of progressive familial intrahepatic cholestasis and Alagille syndrome

Genetic cholestatic liver diseases (GCLDs), including progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome (ALGS), are rare inherited liver disorders that manifest in early childhood and lead to substantial morbidity and healthcare utilization. However, comprehensive data on their economic and humanistic burden in China are scarce. A cross-sectional study was conducted in 2024 among caregivers of GCLD children recruited from a major specialized referral center in China. Data were collected via an online questionnaire covering demographic and clinical profiles, diagnostic pathways, healthcare resource use, direct and indirect costs, and health-related quality of life (HRQoL) using the PedsQL™ Inventory. Caregiver burden was assessed using a Numerical Rating Scale. Univariate and multiple linear regression analyses were performed to identify factors associated with economic burden and HRQoL. Among the 170 patients (PFIC: 41.2%, ALGS: 58.8%), misdiagnosis occurred in 62.4% of cases. The mean age at first visit was 3.9 months, while the mean age at confirmed diagnosis was 11.2 months. The average annual total cost was CNY 244,700 per patient, with direct medical, direct non-medical, and indirect costs accounting for 60.6%, 11.1%, and 28.3% respectively. Both univariate and multivariate analyses revealed that older age and higher family income were associated with better PedsQL scores, whereas disease severity, complications and more frequent follow-up significantly predicted poorer HRQoL. GCLDs confer a significant economic and quality-of-life burden on affected families in China, compounded by diagnostic delays and high out-of-pocket expenses. These findings underscore the need for improved diagnostic accuracy, early intervention, more coordinated rare disease care networks and enhanced psychosocial and financial support policies for this vulnerable population.