AH Cohort and Trials

AH Cohort and Trials

Professor Mark Thursz, Chief Investigator

The clinical studies aim to address challenges in AH management by building on the results of the STOPAH trial. A diagnostic biomarker, taurocholate, arising from metabonomic analyses could replace the need for liver biopsy in most patients. Novel prognostic scores, derived using Bayesian sparse regression, will be used to identify high and low risk patients who might benefit from targeted treatment or early discharge.

MICAH Cohort Study

A prospective MultIcentre Cohort study in Alcoholic Hepatitis (MICAH) is being conducted across the UK at approximately 40 sites. Nested case-control studies for infection, acute kidney injury (AKI) and mortality are being performed to support biomarker validation studies.

MICAH is recruiting all patients with alcoholic hepatitis, irrespective of severity, to evaluate the performance of the prognostic scoring system, diagnostic and prognostic biomarkers. Patients who meet criteria for treatment will receive standard of care.

MICAH is also recruiting a group of patients with decompensated alcoholic liver disease without alcoholic hepatitis to act as controls for validation of the diagnostic biomarker. Clinical and routine laboratory data will be recorded and samples of serum, whole blood, plasma, DNA, stool, PBMC and, in some cases, liver tissue will be taken at baseline. Whole blood, serum and PBMCs will be taken at 7 day intervals during admission and at 90 days.

ISAIAH Trial

IL-1β levels are significantly increased in both serum and liver in patients with alcoholic hepatitis as well as in animal models of the disease. IL-1β is thought to be responsible for many of the clinical and metabolic characteristics of alcoholic hepatitis including fever, neutrophilia, monocyte activation, anorexia and muscle catabolism.

A randomised, placebo controlled trial of IL-1β Signal Inhibition in Alcoholic Hepatitis (ISAIAH) was conducted in 15 centres across the UK. Patients with severe AH were randomised 1:1 to the IL-1β monoclonal antibody canakinumab or placebo to explore the potential benefits of IL-1β inhibition using paired analysis of histological severity at baseline and 28 days. Whole blood 16S-DNA was measured at baseline and sequentially to test performance to predict infection. All patients were given prophylactic antibiotic therapy for 2 weeks. PBMCs taken at baseline and 7 day intervals to 28 days are to be used for immune profiling to determine whether IL-1β inhibition impacts on monocyte antimicrobial function.