NASH is an acronym that stands for Non-Alcoholic SteatoHepatitis. It is the most severe form of non-alcoholic fatty liver disease (NAFLD), and is characterized by the presence of an abnormal accumulation of fat in the liver which in some individuals can progress to liver cell injury (hepatocellular ballooning) and inflammation. Hepatocellular ballooning and inflammation – sometimes called necroinflammation – are commonly considered as the drivers of disease progression, or as the underlying causes of the disease. As NASH evolves, over time it can result in excessive scarring in the liver (fibrosis), a natural response to injury which can lead to liver cirrhosis or liver cancer.

A modern lifestyle disease

NASH is closely related to the triple epidemic of obesity, pre-diabetes, and diabetes, and can be defined as the liver manifestation of the metabolic syndrome. It is heavily influenced by lifestyle (e.g. chronic excessive calorie intake, sedentary activity) and is distinct from other fatty liver diseases caused by alcohol abuse or medication side effects.

A liver manifestation of metabolic disorder

Hypertension

Heart Disease

High Blood Lipids

Insulin Resistance

Type 2
Diabetes

Overweight and Obesity

A life threatening disease

NASH is a chronic yet silent disease, which means that most patients live with it for several years without experiencing any symptoms and are mostly unaware of their liver condition. NASH can progress to more serious disease stages, such as advanced fibrosis, cirrhosis, liver failure or liver cancer.

Liver transplant might then be required, but this is a risky surgical procedure associated with several types of complications, not to mention long waiting lists due to the lack of available healthy organs from donors, or eligibility issues related to patient condition.

Healthy liver

The liver is the most voluminous solid organ in the body, and plays a complex and crucial role. It supplies the organism with many essential functions such as nutrient metabolism protein synthesis, bile production or glycogen storage. A healthy liver is as red as blood with a smooth surface, and it contains 5% (or less) of fat.

Steatosis

Fatty liver, or non-alcoholic hepatic steatosis, is observed in individuals who chronically consume a high caloric diet and/or have a sedentary lifestyle, in the absence of significant alcohol consumption. Excess calories are stored in liver cells as lipids; the liver contains more than 5% of fat and looks pale yellow.

NASH

A substantial fraction of individuals with fatty liver develop chronic cell injury by excess lipid deposition. As a consequence, the liver shows inflammation and cell death (ballooning) in addition to steatosis: these individuals have Non-Alcoholic Steatohepatitis, or NASH. They are also at higher risk of death from cardiovascular disease.

Cirrhosis

Chronic liver cell damage results in wound healing and, as a consequence, the formation of fibrous scar tissue, a process called fibrosis. Patients with a strong scar formation are called “patients at risk of progression”, because they are in danger of a loss of liver function by excessive fibrosis, a state that is called cirrhosis (or stage 4 fibrosis).

Outcomes

Patients with NASH-related cirrhosis are at higher risk of what is called “end-stage liver diseases”, such as loss of liver function (a process called decompensation), liver failure and hepatocellular carcinoma (liver cancer). They are also at higher risk of death from cardiovascular disease and non-liver cancer.


Reference:
EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol, 2016. 64(6): p. 1388-402.