Alagille syndrome (ALGS) is a hereditary condition that affects the body in several ways. ALGS affects the liver and gut but can also cause problems to the heart disease and bones. The disease is evident within 3 months after birth and occurs in 1 in 30,000 to 70,000 births.
Progressive familial intrahepatic cholestasis (PFIC) is a group of hereditary liver disorders. PFIC is estimated to occur in 1 in 50,000 to 100,000 births. Onset usually occurs during early infancy and the condition can lead to serious liver disease.
Individuals with ALGS and PFIC experience itchy skin of varying severity, referred to as pruritus. It is difficult to treat because its cause is not well understood. One substance thought to cause the sensation of itch is bile acid, which is produced by the liver. Treatments that lower bile acid levels can reduce pruritus.
In this study, we will use anonymous routinely collected healthcare data from primary care practices and hospitals in England to describe the characteristics of patients with ALGS and PFIC, both patient populations who experience pruritus, as well as treatments they receive, and investigate the relationship between bile acid levels and the occurrence of pruritus.
Alagille syndrome (ALGS) is a hereditary disorder, evident within 3 months after birth, occurring in 1 in 30,000 to 70,000 births. ALGS manifests as cholestasis, cardiac disease, ocular or skeletal abnormalities, or characteristic facial features, and can lead to end stage liver disease or death.
Progressive familial intrahepatic cholestasis (PFIC) is a group of hereditary liver disorders that cause cholestasis, estimated to occur in 1 in 50,000 to 100,000 births and increases risk of end stage liver disease.
Most individuals with ALGS and PFIC experience cholestatic pruritus (i.e., itchy skin), the underlying mechanisms of which are not well understood and possibly caused by one or more pruritogens like bile acid. Bile acid diffuses into systemic circulation and skin during cholestasis, stimulating pruritogenic neural fibers in the skin, causing itch. Serum bile acid (sBA) is the biomarker for bile acid levels used to evaluate liver function and is typically elevated in cholestatic pruritus. Treatments that can lower sBA levels, such as ursodeoxycholic acid, rifampicin, plasmapheresis and partial biliary diversion, can therefore be effective in treating cholestatic pruritus. There is a lack of real-world evidence investigating the relationship between sBA levels and pruritus.
We aim to use routinely collected primary and secondary care data from England (i.e., Clinical Practice Research Datalink, Hospital Episode Statistics, and Office for National Statistics) to describe the characteristics of patients with ALGS and PFIC, both patient populations who experience pruritus, and their treatment pathway using Sankey diagrams. We will investigate the association between sBA levels and pruritus among individuals with pruritus within 90 days of sBA reading using unconditional logistic regression, as well as explore liver transplant-free survival and pruritus using Cox proportional hazards regression. This work will increase understanding of treatment patterns among individuals with ALGS and PFIC and the relationship between sBA levels and pruritus.
1. Demographic and clinical characteristics of patients with the rare conditions ALGS and PFIC (objective 1)
2. Treatment pathway for ALGS: number and percentage of patients in receipt of relevant treatments using primary care prescriptions and secondary procedures, Sankey diagram (objective 2)
3. Treatment pathway for PFIC: number and percentage of patients in receipt of relevant treatments using primary care prescriptions and secondary procedures, Sankey diagram (objective 2)
4. Risk of pruritus (objective 3)
5. Liver transplant-free survival (exploratory objective 1)
Jennifer Davidson - Chief Investigator - Health iQ Ltd ( UK ) t/a CorEvitas
Caitlin Winton - Corresponding Applicant - Health iQ Ltd ( UK ) t/a CorEvitas
Andre Ng - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
Caoimhe Rice - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
Hannah Brewer - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
Sara Carvalho - Collaborator - Health iQ Ltd ( UK ) t/a CorEvitas
HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation