Pathophysiology of NASH: Have new risk factors been identified?

Nicolas Lanthier Published in the journal : September 2020 Category : Hépato-gastroentérologie

Summary :

Due to the rising prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. NAFLD refers to a disease spectrum that encompasses steatosis and non-alcoholic steatohepatitis (NASH). NASH, which is the inflammatory subtype of NAFLD, has a clear potential of progression to fibrosis and cirrhosis, and can be associated with the need for transplantation. Identification of NAFLD and NASH is important in order to prevent disease worsening and to provide adequate tools for counteracting the causal factors. Risk factors associated with NAFLD and NASH include clinical comorbidities such as the metabolic syndrome, which is more relevant than high body mass index. Further recently identified characteristics, such as dietary composition, intestinal dysbiosis, genetic predisposition, altered brown adipose tissue, muscle alterations, circadian clock disruption or environmental chemicals, are presented in this review.

What is already known about the topic?

• NAFLD (excess fat in the liver) is a common finding (25% of the population on average), and its frequency is increased in case of obesity.

• More severe liver damage with parenchyma inflammation and destruction is possible and is referred to as “non-alcoholic steatohepatitis” (NASH). Despite its importance, NASH remains underdiagnosed in our daily medical practice.

• To date, no pharmacological treatment is available.

What does the article bring up for us?

• More than obesity per se, the presence of excess fat in the abdominal cavity ("abdominal adiposity") confers a risk of liver steatosis and NASH.

• Eating fatty but also sugary foods (especially fructose) leads to fatty liver disease. Low intakes of antioxidant vitamins and excessive consumption of red and processed meats, cooked at high temperatures, may also induce steatosis.

• Some (frequent) genetic mutations, dysfunctional brown adipose tissue, nyctohemeral rhythm disorders, muscle fat infiltration, and environmental chemical exposures are also associated with NASH and represent potential targets for intervention.

Key Words

Non-alcoholic steatohepatitis, metabolic dysfunction-associated fatty liver disease, risk factor, food, microbiota, muscle