This piece was written by one of our contributors; medical student – Mary Moore.
Non-alcoholic fatty liver disease (NAFLD) is an umbrella term used to describe a range of liver conditions related to a build-up of fat deposits in the liver (1).
As NAFLD progresses, it is characterised by increasing fat deposition and inflammation, termed nonalcoholic steatohepatitis (NASH). Later on, the disease is characterised by the formation of scar tissue in the liver (fibrosis), which can result in end stage liver disease, termed cirrhosis (1).
It is important to note that NAFLD is characterised by a buildup of fat in the liver that is not caused by excess alcohol use. If a patient has a history of alcohol abuse and fat in their liver, they may be diagnosed with alcoholic liver disease.
The prevalence of NAFLD is rapidly increasing, particularly in developed nations, such as the United Kingdom. Recent findings report that on average up to 24% of the population in European countries have NAFLD (2,3). A community-based study in the Britain has reported that 26% of its population is predicted to have NAFLD, making it the most common form of chronic liver disease in the country (4). Previously, NAFLD was thought to develop in late adulthood, however, recent studies have shown that children are also at risk of developing the disease (5).
Causes of NAFLD
Presently, experts are still studying the exact causes of NAFLD. Current information suggests that certain conditions put people at risk of developing the disease (6).
NAFLD is linked to the following conditions:
- Overweight or obesity
- Abnormal cholesterol levels (high triglycerides, high LDL cholesterol or low HDL cholesterol)
- Metabolic syndrome – which is defined as the presence of any three of the following:
- large waist size
- high blood pressure
- higher than normal blood glucose levels
- high levels of triglycerides in your blood
- low levels of HDL cholesterol in your blood
- insulin resistance (when cells don’t respond properly to insulin, leading to difficulty managing blood sugar levels)
- an increased risk of developing blood clots
- higher levels of inflammation than usual
- Type 2 diabetes, pre-diabetes or insulin resistance (cells can’t take up sugar in the blood with the hormone insulin)
Studies also show that certain genes increase the risk of developing NAFLD. However, experts are still studying these genes and more research is needed.
These combined health problems appear to promote the deposit of fat in the liver. For some people, this excess fat acts as a toxin to the liver, causing liver inflammation and fibrosis (a buildup of scar tissue in the liver) as disease progresses.
What are the symptoms of NAFLD?
NAFLD is a silent disease with few or no signs or symptoms, even with advanced disease. If symptoms do occur, they may include:
- Discomfort in the upper right abdomen
- Unintentional weight loss
Possible signs and symptoms of advanced disease include:
- Abdominal swelling (ascites)
- Enlarged blood vessels just beneath the skin’s surface
- Enlarged spleen
- Red palms
- Yellowing of the skin and eyes (jaundice)
How is NAFLD diagnosed?
Because NAFLD causes no symptoms, in many cases, it only comes to medical attention when tests are done for other reasons that suggests liver issues. For example, if the liver looks abnormal on an ultrasound or if liver enzymes in a blood test are higher than the expected range.
Tests used to diagnose NAFLD and determine disease stage include (7):
- Liver enzyme and liver function tests
- Fasting blood glucose
- Hemoglobin A1CAdditional blood tests may be completed to rule out other causes of liver disease.
- Computerized tomography (CT) scans
- Magnetic resonance imaging (MRI)
A liver biopsy involves a doctor taking a small piece of tissue from the liver, using a needle. A pathologist will then examine the liver tissue under a microscope to assess for signs of disease (including fat, inflammation and fibrosis).
How is NAFLD treated?
The first line of NALFD treatment is weight loss through a combination of diet and exercise (6-8). Ideally, weight loss of 10% of starting body weight is needed to see significant improvements in disease. However, improvements in disease are also seen at 3-5% weight loss of starting weight.
Other steps to control NAFLD include:
- Healthy diet: A diet rich in whole grains, ‘good fats’ (mono- and poly-unsaturated fats such as those found in: plant-based oils, nuts, seeds and avocado) and moderate in protein should be recommended for patients with NAFLD. Foods containing high amounts of sugar and saturated fats should be limited (8).
- Exercise: Exercise has been shown to be beneficial in the treatment of NAFLD and is most effective when paired with weight loss (8). Current exercise guidelines for the general population are recommended (30 minutes of moderate intensity exercise most days of the week, and strength-based exercise twice per week).
- Control diabetes: The doctor and patient should work together to control blood sugar through diet, exercise and medication.
- Lower cholesterol: The doctor and patient should work together to lower cholesterol levels through diet, exercise and medication.
- Protect Liver from damage: The patient should avoid exposing the liver to unnecessary stress. For example: limit excessive alcohol intake or avoid alcohol altogether, and follow instructions on all medications and over-the-counter drugs.
- Stop smoking: This is advised in order to reduce the risk of having a stroke or heart attack, as those with NAFLD often have a higher risk of heart disease.
According to the European Association for the Study of Liver Disease (EASLD), no medications are approved by drug regulatory agencies to treat NAFLD at this time (6). Drugs such as insulin sensitisers, antioxidants and lipid lowering drugs are used off-label to treat NAFLD but data to support their use are limited.
For those with advanced nonalcoholic fatty liver disease (i.e. cirrhosis), liver transplantation may be considered (6,7).
Indeed, NAFLD prevalence is increasing at an alarming rate in westernised countries and is strongly associated with obesity and the metabolic syndrome. The disease is characterised by increasing fat deposition and inflammation in the liver, in the absence of excessive consumption of alcohol. Currently, there are limited pharmacological treatment options for NAFLD. Lifestyle modifications such as weight loss, a healthy diet and exercise remain the cornerstone of NAFLD treatment. Further, awareness of NAFLD must be promoted in order for prevention, early detection and treatment of the disease.
(1) Brunt, E. M. et al. Nonalcoholic fatty liver disease. Nat. Rev. Dis. Prim. 1, 15080 (2015).
(2) Younossi, Z. et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat. Rev. Gastroenterol. Hepatol. 15, 11–20 (2018).
(3) Armstrong, M. J. et al. Presence and severity of non-alcoholic fatty liver disease in a large prospective primary care cohort. J. Hepatol. 56, 234–240 (2012).
(4) Draijer, L., Benninga, M. & Koot, B. Pediatric NAFLD: an overview and recent developments in diagnostics and treatment. Expert Rev. Gastroenterol. Hepatol. 13, 447–461 (2019).
(5) Williams, R. et al. Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis. Lancet (London, England) 384, 1953–1997 (2014).
(6) EASL; EASD; EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol. 64, 1388–1402 (2016).
(7) Chalasani, N. et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 55, 2005–2023 (2012).
(8) Romero-Gómez, M., Zelber-Sagi, S. & Trenell, M. Treatment of NAFLD with diet, physical activity and exercise. J. Hepatol. 67, 829–846 (2017).