Early Liver Disease Breath Detection
Research type
Research Study
Full title
Breath detection of non-alcoholic steatohepatitis (NASH)-induced metabolic alterations using food flavors.
IRAS ID
330252
Contact name
Serge Engamba
Contact email
Sponsor organisation
Owlstone Medical Ltd.
Clinicaltrials.gov Identifier
Duration of Study in the UK
0 years, 4 months, 4 days
Research summary
The diagnosis of non-alcoholic steatohepatitis (NASH) still requires liver biopsy, an invasive procedure that can lead to complications. Impaired hepatic function, associated with chronic liver diseases, changes the metabolic pathways responsible for the biotransformation of certain volatile organic compounds (VOCs) exhaled in breath. Consequently, abundance of these VOCs on breath changes in the presence of chronic liver diseases and could be used as a non-invasive diagnostic tool. To date, identified VOCs with classification performance for chronic liver diseases are of exogenous origin and their abundance on breath is not only related to liver malfunction, but also to the extent of the everyday exposure to these compounds, mainly through dietary intake. To overcome this limitation, we established the exogenous volatile organic compound (EVOC) approach, based on the administration of a defined dose of a compound followed by its measurement on breath at different timepoints. We tested several compounds in healthy subjects and found that their levels on breath peak ~10 minutes after administration, followed by a progressive reduction. NASH-associated alterations of gene expression, and/or impaired hepatic function is expected to alter the reduction of administered compound on breath allowing for classification between NASH subjects and healthy controls.
We plan to administer a cocktail of EVOCs made of limonene, benzyl alcohol, 2-pentanone, 2-butanol, and nonanal, compounds safe for human consumption, approved, and widely used in the European Union as food flavoring agents. The amounts we will administer are well below thresholds found to cause side effects in human or animal models. The working hypothesis is that NASH-induced changes of hepatic clearance of administered food flavors alters their amounts measured in breath allowing differentiation between NASH and healthy liver conditions.
We aim to conduct a cross-sectional study with the objective to identify if changes in EVOCs metabolism have a diagnostic potential for subjects with advanced fibrosis. Subjects with FibroScan-confirmed fibrosis are asked to fast overnight. Then they provide a baseline breath sample, followed by oral administration of the EVOCs cocktail, and sampling of additional breath samples at subsequent timepoints up to 90 minutes post ingestion.
REC name
London - Riverside Research Ethics Committee
REC reference
23/PR/1083
Date of REC Opinion
23 Oct 2023
REC opinion
Further Information Favourable Opinion