What causes non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases that all start off with a simple fatty liver. To produce this, NAFLD is closely linked to:

• Overweight and obesity
• Insulin resistance
• High blood glucose levels (as in the case of uncontrolled pre-diabetes or diabetes)
• Hyperlipidaemia (high levels of fat in the blood)

Research shows that fructose consumption is a major player in the development of NAFLD. This simple sugar that’s found in many plant foods, especially fruit, is mostly metabolised by the liver, where it can cause oxidative stress (see below). Overconsumption of fructose (for example in the form of fruit juice), as well as an inactive lifestyle and an unhealthy diet all contribute to NAFLD.

On the other hand, fruit is a good source of health-boosting antioxidants, so they mustn’t be excluded from the diet either. The recommendation is to steer clear of fruit juices (a concentrated form of fructose) and to eat two to three portions of whole fruits per day instead. 

To progress to NASH is somewhat more complex, and researchers are still exploring all the mechanisms involved. But, according to the American College of Gastroenterology, possible causes include:

• Oxidative stress. This refers to an imbalance between the production of harmful free radicals and the body’s ability to counteract or “detoxify” their harmful effects through neutralisation by antioxidants.
• The production and release of toxic inflammatory proteins called cytokines by the inflammatory liver or fat cells.
• Liver cell necrosis (death).
• Inflammation of the adipose (fat) tissue and infiltration of these tissues by white blood cells.
• An imbalance in the gut microbiota (the intestinal bacteria) may also play a role in liver inflammation.

Note that certain medications (e.g. amiodarone, methotrexate, tamoxifen, valproic acid, glucocorticoids), as well as inborn errors of metabolism, could also cause NAFLD. However, this is less common and the mechanism by which it occurs is very different.

Reviewed by Dr Mark Sonderup, B Pharm, MB ChB, FCP (SA). Senior Specialist, Division of Hepatology, Department of Medicine, University of Cape Town and Groote Schuur Hospital. July 2018.