Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disease occurring in the absence of excessive alcohol consumption that ranges from isolated hepatic triglyceride accumulation (steatosis, NAFL); through hepatic triglyceride accumulation plusinflammation and hepatocyte injury (non-alcoholicsteatohepatitis, NASH); and ultimately progresses to fibrosis/cirrhosis and potentially hepatocellular carcinoma (HCC)1.

NAFLD is a common condition, strongly associated with the Metabolic Syndrome (obesity, type 2 diabetes mellitus (T2DM) and dyslipidaemia) and characterised by substantial inter-patient variability in severity and rate of progression. An important paradox exists: a significant proportion of the population have NAFLD but only a minority progress to advanced liver disease or morbidity/mortality1,2.

The transition from NAFL to NASH and the stage of fibrosis are important discriminators between a relatively benign prognosis and an increased risk of morbidity/mortality1,3. Liver biopsy remains the established but imperfect ‘gold standard’ investigation being invasive, resource intensive,prone to sampling error and carrying a small but significant risk of complications4. Such invasive tests are not practical outside specialist practice, and are particularly unsuitable with such a large ‘at risk’ population.

A lack of tractable non-invasive biomarkers has impeded the diagnosis, risk stratification and monitoring of patients2. It has also hampered drug development and the conduct of clinical trials, which still depend on histological effect as an endpoint. The overarching aim of LITMUS is to develop, robustly validate and advance towards regulatory qualification biomarkers that diagnose, risk stratify and/or monitor NAFLD/NASH progression and fibrosis stage. Success will help target care to those at greatest risk, facilitate drug development and ultimately give patients access to approved medicines.


  1. Anstee, Q. M., Targher, G. & Day, C. P. Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol10, 330-344, doi:10.1038/nrgastro.2013.41 (2013).
  2. Anstee, Q. M., McPherson, S. & Day, C. P. How big a problem is non-alcoholic fatty liver disease? BMJ343, d3897, doi:10.1136/bmj.d3897 (2011).
  3. Ekstedt, al.Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology61, 1547-1554, doi:10.1002/hep.27368 (2015).
  4. Ratziu, al.Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology128, 1898-1906 (2005).
Copyright © 2023 LITMUS Project

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 777377. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. Visit IMI.

The information contained in this website reflects only the author's view. Neither IMI nor the European Union, EFPIA, or any Associated Partners are responsible for any use that may be made of the information it contains.