Pruritus or itch is a common and often troublesome symptom in Primary Biliary Cirrhosis (PBC) and other cholestatic liver diseases. The cause of cholestatic itch is incompletely understood and currently available therapies are only partially successful in symptom relief.
The first phase of this research project involves studying a novel therapeutic agent [Ileal Bile Acid transport (IBAT) inhibitor] in a phase 2 randomised controlled multi-centre trial in collaboration with GSK Pharma. In addition to the safety and tolerability of this drug, the effect of IBAT inhibitor on known metabolites of itch such as bile acid species, autotaxin and FGF-19 will also be studied.
The second phase of research involves Metabonomics and Microbiomics which are state of the art ‘omic’ technologies to study the metabonomic and microbiomic ‘signatures’ of itch in PBC. This will involve recruiting matched PBC patients with no itch and healthy volunteers to serve as comparator group to itchy patients recruited in the clinical trial. Using metabonomic techniques analyses of serum, urine and bile to identify (novel) metabolites associated with pruritus. Similarly microbiomic techniques will be applied to stool samples to identify changes in gut microbiota (dysbiosis) associated with pruritus in PBC.
Results of this research are likely to inform the pathophysiology of itch in PBC which in turn may help to identify biomarkers and develop better therapy for patients in future.