Research & Development

Scientific Background

NAFLD / NASH

NAFLD

Non-Alcoholic Fatty Liver Disease (NAFLD) affects about 30% of the population in developed countries. This disease is also now recognized as one of the most common liver disorders, and a significant and growing public health problem1. In the US alone, More than 100 million people are affected by NAFLD, and its prevalence is rapidly growing in parallel with metabolic syndromes, particularly obesity and diabetes. In the US and Europe, the economic burden on primary care due to NAFLD is currently estimated at $76 billion2.

NAFLD is characterized by the accumulation of fat of 6% or greater in the liver of people who only drink alcohol in moderation, or not at all. There may be numerous causes of NAFLD, however, the disease is mostly associated with a high fat, fructose-rich diet. Although NAFLD is generally asymptomatic, it is a major risk factor for liver inflammation (NASH) and scarring (fibrosis and cirrhosis). In addition, NAFLD is also associated with metabolic syndrome and cardiovascular disease. Currently, NAFLD can only be managed through lifestyle improvements, such as weight reduction and physical activity.

NAFLD

NASH

Non-Alcoholic Steato-Hepatitis (NASH), a more severe form of NAFLD, affects 4%-6% of the population and is associated with increased risk of liver cirrhosis, liver failure, hepatocellular cancer, as well as metabolic and cardiovascular diseases. The major characteristics of NASH are elevated liver fat along with inflammation and fibrosis.

Despite the growing need, there are currently no approved therapeutic treatments for NASH. The “standard-of-care” treatment includes life style changes, such as low-calorie and low fat diets, and physical activity. However, for most of the population, such life style changes are known to be difficult to maintain in the long term.

While there are no approved therapeutics for the treatment of NASH, some drugs are prescribed off-label. However, the efficacy of such drugs have not been proven in well-designed clinical studies. In particular, the anti-diabetic drug, Metformin®, is used for patients who have type 2 diabetes (T2DM) as well as NASH. Other drugs such as Orlistat (Xenical®, Roche) and Glitazones have been banned for use due to severe side effects.

Currently, it is impossible to predict which of the NAFLD patients will deteriorate to NASH as it is unclear what causes NASH to develop. Researchers are now focusing on several factors that may contribute to the development of NASH. Therefore lifestyle changes are recommended for all patients with NAFLD.

NAFLD/NASH are now widely considered to be the liver diseases of metabolic syndrome, which is a major precursor and cause of atherosclerosis and its complications. Concordant studies in the last 5 years in Europe and Japan have demonstrated that, over a follow-up period of 5-6 years, patients with NAFLD develop major cardiovascular complications (myocardial infarction, coronary bypass), some 500% more frequently than controls.

[1] World Gastroenterology Organisation Global Guidelines “Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis” June 2012

[2] Based on estimated UK cost of £4.2 billion: Aylott J, et al., Tackling Obesities: The Foresight Report 2007.