DEFINING THE GENETIC DRIVERS OF ADULT-ONSET CHOLESTATIC LIVER DISEASE

Condition(s) studied

Investigational drug(s) / intervention(s)

Advanced Whole Genome Sequencing to Identify Rare Pathogenic Variants in Unexplained Cholestatic Liver Disease: The intervention consists of advanced genetic analysis to identify the presence of rare harmful variants in genes known to be associated with cholestasis or in other genes related to liver disorders. The results from the cases will be compared with WGS data from a large group of 1025 healthy controls (previously collected within the FOGS study) to assess the enrichment of these variants. The primary objective is to establish the prevalence of pathogenic variants, while secondary objectives include identifying new potential genetic determinants to improve diagnostic accuracy and optimize the clinical management of these complex conditions.

Study summary

Cholestatic disease in adults comprises a heterogeneous group of conditions characterized by intra- or extrahepatic alterations of bile flow that can lead to fibrosis or hepatic decompensation. Due to the heterogeneity of clinical manifestation, which is sometimes very subtle, diagnosis based on clinical, histological, and radiological evaluation is often very complicated. Genetic testing can be helpful in identifying the cause of the clinical phenotype, thereby allowing for targeted follow-up adequate to the patient's specific characteristics and risk factors. Although the utility of genetic analysis has been well documented for other liver diseases or in pediatric cohorts of children with cholestatic disease, the use and benefits of genetic testing in adults with cholestatic disease are still little explored and investigated. In this context, through the use of whole-genome sequencing (WGS), the FIRST project aims to evaluate the role of rare genetic variants in the pathogenesis of cholestatic disease and the utility of WGS in defining a genetic diagnosis.

Eligibility

Primary outcome measure(s)

• Primary Endpoint: Diagnostic Yield of Whole Genome Sequencing (WGS) in Adult Patients with Unexplained or Atypical Cholestasis — 9 months
  The Primary Endpoint is the determination of the prevalence of pathogenic variants in genes already known to be involved in genetic cholestasis, effectively assessing the diagnostic yield of the WGS approach in adult patients with unexplained or atypical cholestasis.

Trial sites (1)

More Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico trials in Italy

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