NUL-FAT
There is a strong need for more precise tools to diagnose and monitor various obesity phenotypes. Fat infiltration in the liver plays a pivotal role in developing several obesity-related co-morbidities, and the present project will validate the performance of a novel ultrasound method for quantitative measurements of liver fat fraction for early diagnostics and treatment monitoring.
Background
NAFLD is strongly associated with overweight, and the prevalence has increased significantly during the last decades and is now the major cause of chronic liver disease, including non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Equally relevant is NAFLD in milder forms as indicator of a metabolically active stage obesity and development of obesity-related comorbidities. Low-grade fat tissue inflammation and mitochondrial dysfunction appears to be a key pathophysiological mechanism in development of obesity related comorbidities, including diabetes, cardio-vascular disorders and cancers. Although the risk of NAFLD is highly increased in obesity it is frequent also in non-obese individuals, reflecting a huge variation in the threshold for having excessive fat infiltrating visceral organs including the liver. Early diagnosis of NAFLD is of great benefit to patients as total regression of liver fat is achievable at early stages of NAFLD, e.g. in response to weight reduction. However, today precise and early accessible diagnostic tools to reveal low-grade NAFLD are not available, and cost-effective drugs to support dietary treatment is lacking.
This project will recruit a unique study population with mild NAFLD and through a multidisciplinary research collaboration validate a novel ultrasound method that holds the potential of screening risk population by a point-of -care solution. We will also explore potential biomarkers (lipidomics) based on promising animal studies and test the efficacy of a mitochondria activating fatty acid on NAFLD remission in a Phase 1 study.
Objective
Main objective is to develop a precise, easy-to-use (point-of-care) methodology for diagnosing NAFLD at an early stage, and to test the efficacy of a novel promising bio-active fatty acid as add- on treatment to calorie restriction.
Subobjectives: 1) Validating a novel ultrasound tool for quantitative measurement of liver fat fraction in patients with NAFLD and comparing the performance with state-of-the-art MRI methods, 2) Pilot testing of a bio-active Mitochondria-Targeting Fatty Acid (MTFA) in patients with NAFLD and 3) Exploring lipidomics as novel diagnostic and prognostic biomarkers related to NAFLD.
Impact
The novel ultrasound method holds the potential of a point-of-care ultrasound solution that could be used at all levels of healthcare services. Combined with new biomarkers that are clinically useful in diagnosis, risk stratification and monitoring of treatment effects in patients with mild NAFLD the project results might enable evidence-based personalized guidance and treatment to patients at risk of being metabolic unhealthy – beyond the present imprecise level of BMI. Successful early treatment of NAFLD will reduce the risk of severe comorbidities including several cancers, diabetes, cardiovascular diseases, and mental health illnesses for large number of patients.
The project builds a platform for future studies of various related research questions, including health service development and health economic evaluations.
Period
2021-2027
Contact
Rønnaug Ødegård
Dissemination
Solberg, S., N. Amini, Y. Zaza, B. A. Angelsen and R. Hansen (2023). "Estimation of fat content in soft tissues using dual frequency ultrasound—A phantom study." The Journal of the Acoustical Society of America 153(3): 1766-1775.
Funding
Total budget: 9800 000 NOK
Funding bodies: Central Norway Health Authorities
Collaborators
CORI/St Olav University Hospital leads the project.
Collaborators: NTNU-IKOM v/ Reidar Fossmark, professor, SINTEF Digital v/ Sigrid Berg, research leader and the start-up companies SURF Technology and TOmega