Innovative diagnosticsand therapeuticsfor metabolic disease

Non-Alcoholic Fatty Liver Disease

CellMade's mission is the discovery of novel biomarkers and the co-development of medical nutrition products for the early diagnosis and preventive treatment of NASH

"I'm not obese, I'm just big boned". Is there truth to heavy weight because of big bones and big frame? Not really. Naturally, from a medical perspective, there is no such thing as being "big boned"; sadly, what is true is the endemic problem of overweight and Obesity. According to the OECD, 34.6% of the adult population in the EU 27 countries is overweight, and 15.5% is obese. Even more startling is the noxious chain effect ignited by Obesity, which is correlated to Non-Alcoholic Fatty Liver Disease (NAFLD), in turn associated with a broad spectrum of co-morbidities, including Type-2 Diabetes Melitus (T2DM) and Cardiovascular Diseases (CVD).

 

The healthcare cost and burden to society will sky rocket in the next years and is estimated to reach US$35 billion by 2025.

 

Non-Alcoholic Fatty Liver Disease is defined by the presence of a determined hepatic steatosis, which corresponds to an accumulation of triglycerides in hepatocytes representing more than 5% of the total weight of the liver, in the absence of significant alcohol consumption, of the use of steatogenic drugs (tamoxifen or amiodarone) and of another liver pathology (viral or autoimmune hepatitis, hemochromatosis, Wilson's disease, …). NAFLD distinguishes liver steatosis (non-alcoholic fatty liver, NAFL) from non-alcoholic steatohepatitis (NASH) (Chalasani et al. 2012). NAFL, which corresponds to the first stage of NAFLD and is considered to be a benign, asymptomatic and reversible condition, is defined by the presence of hepatic steatosis (≥ 5%) without evidence of hepatocytes ballooning (Chalasani et al. 2012; Neuschwander-Tetri 2003; Spengler and Loomba 2015).

 

In some patients, NAFL may progress to a serious and irreversible pathological condition, non-alcoholic steatohepatitis (NASH), which is characterized by the presence of hepatic steatosis associated with inflammation and hepatocytes ballooning that causes their dysfunction and death. This condition, which may or may not be accompanied by the presence of fibrosis, may progress to cirrhosis, liver failure and, in rare cases, to liver cancer (Chalasani et al. 2012; Spengler and Loomba 2015).

 

Based on an epidemiological study that identified NAFLD cases in published scientific studies, the overall prevalence of NAFLD is 25%.  In a worrying way, this prevalence increased sharply, from 15 to 25% between 2005 and 2010 (Younossi et al. 2016).

 

While NAFL remains considered as a benign and poorly symptomatic condition, its progression to NASH and the onset of co-morbidities, such as atherosclerosis or type 2 diabetes mellitus (T2DM), are major health problems. Among the leading causes of death in NAFLD patients, cardiometabolic complications are extremely common, including coronary heart disease and T2DM (Rafiq et al. 2009).

 

The ever-increasing pandemic of Obesity fuels NAFLD prevalence and, as such, NASH has become one of the most common liver disorders. NASH is a critical public health concern with high unmet medical needs and remains widely untreated. Despite major efforts by the industry, no approved therapies are marketed.

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