Non-alcoholic fatty liver disease (NAFLD)

NAFLD, NASH, MASLD and MASH

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide (prevalence estimates ranging from 25% to 45% in most studies), increasing in parallel with that of obesity and diabetes.

In the US, about one-third (100 million adults) of the population is affected by NAFLD, and 5% by nonalcoholic steatohepatitis (NASH), respectively.

As demonstrated in the RISC (relationship between insulin sensitivity and cardiovascular disease) population of apparently healthy people, the prevalence of a fatty liver associates with insulin resistance (as measured with the hyperinsulinemic euglycemic clamp technology), coronary heart disease risk, and signs of early atherosclerosis. Patients with NAFLD overall, and those with NASH in particular, are at increased risk of mortality from liver disease (13%), and more commonly from cardiovascular disease (25%) and malignancy (28%) [Rinella ME, JAMA 2015; 313: 2263-2273].

Due to the strong association of fatty liver disease with metabolic disturbances, the nomenclature was changed in a recent consensus process. NAFLD is now called MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease) and NASH was renamed into MASH (Metabolic dysfunction-Associated SteatoHepatitis) [Rinella ME, J Hep 2023]

Profil and clinical trials on MASLD

Profil has all the relevant tools available for exploratory mechanistic and early-phase clinical trials addressing MASLD-relevant endpoints

MRI-PDFF for quantification of liver fat (in collaboration with external partner)
MRS for assessment of the hepatic metabolism including quantification of glucagon (in collaboration with external partner)
Quantification of endogenous glucose production and hepatic insulin sensitivity by means of a two-step hyperinsulinemic euglycemic clamp
Addressing the metabolic communication between adipose tissue and the liver with an integrated methodological approach combining indirect calorimetry, glycerol kinetics and air displacement plethysmography
Measurement of fat and glucose oxidation via indirect calorimetry combined with a standardized dietary regimen
Assessment of lipolysis (microdialysis, glycerol kinetics) and hepatic VLDL secretion
Comprehensive and specifically tailored blood-based assaying of biomarkers and surrogates
Blood sampling for the profiling of fatty acid signatures in the plasma-free fatty acid fraction
Stratification for genetic polymorphisms determining the clinical outcome of fatty liver and of pharmacological interventions
Preparation of adipose and muscle tissue biopsies for histopathological analyses, metabolomics and gene expression
Preparation of muscle tissue biopsies for analyses of mitochondria and oxidative metabolism