Angelo Corso Faini, Michele Pinon, Giulia Margherita Brach Del Prever, Carmelo Maria Romeo, Maria Luca, Fiorenza Mioli, Claudia Saglia, Caterina Scolari, Tullia Carradori, Francesca Arruga, Cristina Chiadò, Anna Morgando, Silvia Martini, Renato Romagnoli, Elisabetta Bugianesi, Diana Carli, Tiziana Vaisitti, Silvia Deaglio, Pier Luigi Calvo
Genetic testing plays an important role in the diagnosing of liver diseases, but its diagnostic performance varies across patient populations. By analyzing diagnostic yield across patient subgroups, this study aims at defining age-tailored diagnostic workflows for a more effective integration of genetic testing into clinical practice. We retrospectively analyzed 203 patients (145 children, 58 adults) with acute or subacute liver disorders of suspected genetic origin who underwent next-generation sequencing, categorized them by clinical diagnosis, and evaluated diagnostic yields to develop age-tailored testing workflows. The median age was 8 years; 65.5% were male, 84.7% White, and 27.6% had undergone liver transplantation. Cholestatic liver disorders (30%) and unexplained liver dysfunction (20.2%) were the most common indications for testing. Overall, genetic testing achieved a definitive diagnosis in 35.5% of patients, with a higher yield in children than adults (41.4% vs. 20.7%). Metabolic disorders had the highest diagnostic yield (83.3%), while PFIC/BRIC and Alagille syndrome were the most frequent genetic diagnoses. Age-specific diagnostic workflows retrospectively enriched the overall diagnostic rate by approximately 11% across age and disease categories. These findings demonstrate that tailoring genetic testing strategies to patient age and clinical presentation can improve diagnostic efficiency and support a standardized integration of genetic testing into hepatology practice.