Serum taurocholate was identified to be a candidate diagnostic marker of AH from a pilot study and demonstrated increased sensitivity when expressed as a ratio to bilirubin.
We will develop and employ an accurate quantitative ultra-performance liquid-chromatography (UPLC)-MS/MS method adapting the method of Sarafian to measure taurocholate and bilirubin in serum samples, which will also capture concentrations of other tauro- and glyco-conjugated bile acids. In order to probe the aetiology of elevated serum taurocholate, we will measure the intrahepatic levels of glycine and taurine using a validated targeted UPLC-MS/MS method with precolumn derivatisation with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQTag Ultra). We will measure a panel of serum eicosanoids using a targeted UPLC-MS/MS method to establish the nature of inflammatory responses in AH, which can be associated with gut microbial changes in AH.
These assays will be carried out within the MRC-NIHR National Phenome Centre. Using validated in house analytical pipelines for spectroscopic analysis, preprocessing and data modelling we will aim to stratify patients based on their prognostic risk. We will use dynamic modelling methods to capture time-dependent behaviour of key metabolite sets and will subsequently employ biomarker recovery tools to identify relevant mechanistic pathways that may give insight into pathogenesis and/or prognostic response to subsequent therapeutic interventions utilizing an established pharmacometabonomic framework. These data will be co-modelled with other data modalities in the Biostatistic workstream.
Downstream, we will seek to deploy the taurocholate assay in clinical environments using a method adapted for a TQmicro platform.
Clinical Research Fellow