DEFINING THE GENETIC DRIVERS OF ADULT-ONSET CHOLESTATIC LIVER DISEASE

Inclusion criteria

Cases:

• Adults, aged > 18 years with:

• 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);
• 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;
• 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