Cholestatic liver diseases (CLDs), result in severe impairment of liver function and ultimately in liver failure. Patients with these diseases suffer from severe persistent itch and failure to thrive (in young children), and may develop hepatocellular carcinoma.
Due to the lack of long-term effective pharmacological treatment options, liver transplantation is often necessary for survival. Unfortunately, suitable donor livers are scarce, and liver transplantation and post-transplant care are very costly and burdensome for the patient. Additionally, the life-long immunosuppressive treatment following transplantation profoundly reduces quality of life.
CLDs can have widely varying causes of disease, but the common denominator of all CLDs is hepatic and systemic accumulation of bile acids, which become toxic at these high concentrations because of their lipid-dissolving properties. The team of investigators driving this project aims to reduce the development of liver damage in patients with CLDs of various etiologies, thereby alleviating symptoms (including itch, growth retardation) and preventing or delaying the need for liver transplantation which now often has to be performed already in childhood. The approach that will be developed in this Biotech Booster project encompasses modulation of pathways in hepatic bile acid metabolism that so far have not been exploited for this purpose. Preclinical work has demonstrated the efficacy of this approach in various CLD models.
