While the progression of the disease from isolated steatosis, or non-alcoholic fatty liver, to NASH is not yet fully understood, experts have established a clear and strong relationship between disease progression and several metabolic conditions.
The World Health Organization defines obesity as an excessive fat accumulation and a Body Mass Index (BMI) greater than or equal to 30. The presence of visceral fat in the abdomen is associated with metabolic impairment and higher risk of metabolic disorders such as insulin resistance or NAFLD. The prevalence of NASH among obese populations is approximately 25 to 30% while some studies suggest that it goes up to 12% in the general population.
Type 2 diabetes
In patients suffering from type 2 diabetes, organs such as the liver do not respond effectively to insulin, the hormone produced by the pancreas that is responsible for glucose regulation. Type 2 diabetes is thus characterized by chronic hyperglycemia in conjunction with insulin resistance. Patients with NASH and type 2 diabetes have a higher risk of progression to cirrhosis or liver cancer.
Although its definition is still being debated within the scientific community, metabolic syndrome can be defined as the presence of at least three of following clinical presentations: abdominal obesity, hypertriglyceridemia, hyperlipidemia (i.e. low HDL cholesterol, high LDL cholesterol, high total cholesterol), high blood pressure, and high fasting blood glucose levels. In patients with NAFLD, the presence of the metabolic syndrome more than triples the risk of progressing to NASH and severe fibrosis.
Insulin resistance is closely related to obesity and physical inactivity. This chronic metabolic disorder is likely to be involved in NASH etiology because of the central role it plays in promoting the release of fatty acids from visceral fat, transferring free fatty acids to the liver, and synthesizing lipids in the liver. NASH patients with insulin resistance are at higher risk of developing liver fibrosis.
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Younossi, Z.M. et al., Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 2016. 64(1): p. 73-84.