Finding genetic causes of adult-onset cholestatic liver disease
DEFINING THE GENETIC DRIVERS OF ADULT-ONSET CHOLESTATIC LIVER DISEASE
This study uses whole-genome sequencing to try to find rare genetic causes in adults with unexplained cholestatic liver disease so care can be better tailored.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico Academic / other |
| Locations | 1 site (Milan, Milano) |
| Trial ID | NCT07317193 on ClinicalTrials.gov |
What this trial studies
The project performs advanced whole-genome sequencing on adults who have persistent or atypical cholestatic liver disease, including cases with negative or no prior genetic testing. Eligible participants are identified by prolonged elevations of alkaline phosphatase or GGT, atypical features of PSC, seronegative PBC, or a family history of unexplained cholestasis. Sequencing data will be analyzed to identify rare pathogenic variants that might explain the clinical presentation. Genetic diagnoses found could inform monitoring, treatment decisions, and family counseling.
Who should consider this trial
Good fit: Ideal participants are adults over 18 with persistent unexplained elevations of ALP or GGT for at least six months, atypical PSC or seronegative PBC, or a family history of unexplained cholestasis, especially if prior genetic testing was negative or not performed.
Not a fit: Patients with a clear non-genetic cause of cholestasis (for example obstructive biliary disease, active viral hepatitis, or drug-induced liver injury) or those with an established genetic diagnosis are unlikely to benefit.
Why it matters
Potential benefit: If successful, this work could identify genetic diagnoses that enable personalized monitoring, targeted therapies, and family testing.
How similar studies have performed: Genetic testing including whole-genome sequencing has proven helpful in pediatric cholestasis and other liver diseases, but its use specifically in adult-onset cholestasis remains relatively untested.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: Cases: * Adults, aged \> 18 years with: 1. persistent or intermittent elevations in serum alkaline phosphatase (ALP) or gamma-glutamyltransferase (GGT) for at least six months not explained following standard diagnostic assessment adhering to the guidelines of the European Association for the Study of the Liver (EASL), or with a positive family history of unexplained cholestasis or hepato-biliary cancer, negative to previous genetic tests (targeted panel for PFIC genes or WES); 2. primary sclerosing cholangitis (PSC) with unusual features: small-duct PSC, non-typical radiological findings according to radiological guidelines on PSC, absence of concomitant inflammatory bowel disease, negative to previous genetic tests (targeted panel for PFIC genes or WES) or who didn't perform previous genetic test; 3. primary biliary cholangitis (PBC) without specific anti-mitochondrial antibodies, negative to previous genetic tests (targeted panel for PFIC genes or WES) or who didn't perform previous genetic test. * Signature of informed consent Controls: -Blood donors (age 18-65 years) without clinical signs of liver diseases based on the collected clinical parameters: anthropometric (BMI\>18 and \<25), haematological (Hb, white blood cells, platelets within the reference range), biochemical traits (albumin, bilirubin, AST, ALT, GGT, ALP within the reference range), medical history (negative for chronic or concomitant diseases, including immunological diseases) Exclusion Criteria: Cases: * Patients who do not possess the above inclusion criteria or have at least one of the following exclusion criteria: * an already known genetic diagnosis explaining the clinical phenotype * affected by other causes of liver disease such as viral or autoimmune hepatitis Controls: -Blood donors with clinical signs of liver diseases
Where this trial is running
Milan, Milano
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Istituto di Ricovero e Cura a Carattere Scientifico di natura pubblica — Milan, Milano, Italy (Recruiting)
Study contacts
- Study coordinator: Luisa Ronzoni, Doctor
- Email: luisa.ronzoni@policlinico.mi.it
- Phone: 02.5503.4101
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.