The MRC Stratified Medicine application entitled ‘Minimising Mortality from Alcoholic Hepatitis’ will commence in April 2018 and will last for 5 years. The award was for £5M and will involve Imperial College (Mark Thursz, Harry Antonaides, Elaine Holmes), University of Birmingham (David Adams, Trish Lalor, Chris Weston), University College London (William Rosenberg), MRC Biostatistics Unit Cambridge (Paul Newcombe), University of Edinburgh (Stuart Forbes) and University of Plymouth (Ashwin Dhanda) as well as the 40 clinical sites recruiting patients. 

The programme will include clinical trials and an observational cohort study: 

1.  IL-1 Signal Inhibition for Alcoholic Hepatitis (ISAIAH) trial. A randomised double blind placebo controlled trial in patients with severe alcoholic hepatitis evaluating the efficacy of Canakinumab (anti-IL-1 monoclonal). 54 patients

2. Multicentre cohort study in alcoholic hepatitis (MICAH): recruiting patients with mild, moderate and severe alcoholic hepatitis and controls with acute-on-chronic liver failure / acute decompensation as controls. The purpose is to  

(a) evaluate the predictive value of bacterial 16S-DNA (and fungal 18S-DNA)  levels in blood for infection and to guide the use of prophylactic antibiotics. 

(b) assess the diagnostic utility of taurocholate to distinguish alcoholic hepatitis from other causes of liver failure

(c) develop novel prognostic biomarkers (including ELF and procalcitonin) 

(d) develop a new prognostic scoring system

(e) identify the negative regulators of regeneration using gene expression profiles in liver tissue

(f) provide samples to investigate mechanisms of immune paresis

(g) evaluate the BLISS assay for steroid resistance as a marker of treatment response/prognosis

3. Mechanism of Action of an FXR Agonist in AH (MAFIA) trial to assess the pharmacokinetics and efficacy of obeticholic acid in alcoholic hepatitis.