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What is nonalcoholic fatty liver disease?

Nonalcoholic fatty liver disease (NAFLD) is an umbrella term for chronic liver diseases that occur in people who drink little or no alcohol. Nonalcoholic fatty liver disease is characterized by the build-up of excess fat in liver cells. Fatty liver occurs if more than 5 to 10% of the liver’s weight consists of fat.

Nonalcoholic fatty liver disease is divided into nonalcoholic fatty liver (NAFL, also known as steatosis) and nonalcoholic steatohepatitis (NASH). Though NAFL and NASH are both characterized by fat accumulation in the liver, NASH is also accompanied by inflammation. About 5-10% of NAFLD cases are NASH, and about one-third of NASH cases progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma.1

Nonalcoholic fatty liver disease is a very common disease. The prevalence of NAFLD in adults has ranged from 20-30% in industrialized countries. In the U.S., the prevalence of NAFLD is estimated to be 24%, and it is more common in people over 50 years old.2

is the most common type of liver cancer affecting people with chronic liver diseases, such as cirrhosis.

What are common symptoms?

The majority of NAFLD cases are asymptomatic, although some NASH patients experience fatigue, malaise, and mild, right upper abdominal discomfort.3 Many patients with NAFLD are overweight or obese and have normal liver function test results. Therefore, detection of NAFLD often occurs through a routine health evaluation, or during an abdominal ultrasonography.1

What are the causes?

The exact cause of NAFLD is not fully understood, but it is believed to be caused by multiple factors. The main cause of NAFLD is the accumulation of dietary sugars and fats in the liver. If enough of these substances accumulate, they lead to the generation of lipotoxic metabolites. These metabolites can cause liver injury, which – in conjunction with NAFLD risk factors – cause the disease to continually worsen.1,4

Risk factors of NAFLD are (in order of relevance)1,5:

  • Obesity
  • Hypertension
  • Insulin resistance
  • Genetic and epigenetic factors
  • High-fat and high-sugar diet
  • Altered gut microbiota
are lipidic or fatty substances that accumulate in non-adipose (non-fatty) tissue, causing cellular dysfunction and cellular death.

How does this topic relate to my microbiome?

Blood carries toxins produced by the gut microbiota to the liver. As a result, the gut microbiome affects the development and progression of NAFLD through what is known as the gut-liver axis. Gut dysbiosis leads to the overproduction of fatty acids in the bowel and increased small bowel permeability, which help activate inflammatory pathways. These pathways are related to the development of insulin resistance, obesity, fat accumulation in the liver, and liver injury.6,7

Escherichia coli, an alcohol-producing bacteria, is more abundant in NAFLD patients and is associated with increased gut permeability. Also, NAFLD patients have more inflammation-promoting Streptococcus and less inflammation-preventive Ruminococcaceae.8

Which diseases/topics are related to nonalcoholic fatty liver disease?

Common comorbidities of NAFLD patients are (in order of frequency)2,4:

  • Obesity
  • Insulin resistance or type 2 diabetes
  • Dyslipidemia (an increase of fat cells in the blood)
  • Hypertension
  • Metabolic syndrome
  • Hepatocellular carcinoma

Since all of these conditions are also risk factors for cardiovascular diseases, heart-related conditions are one of the leading causes of death in patients with NAFLD.

is a group of diseases – such as hypertension, obesity, high blood pressure, and high cholesterol – which increase the risk of heart disease, stroke, and diabetes.

How can people take action?

A healthy lifestyle (eating healthfully, reducing sugar intake, exercising regularly, and maintaining a healthy body weight) is the best way to lower your risk of the disease. For patients with NAFLD, lifestyle interventions that include weight loss and dietary changes (like adopting a Mediterranean diet) are associated with improved liver health.4,5

Since NAFLD is often asymptomatic, detection of the disease occurs through regular health screening. If you have any risk factors – such as obesity, hypertension, or insulin resistance – visit your healthcare provider regularly. If NAFLD is diagnosed, your healthcare provider might suggest lifestyle changes, medications, or further testing and specialist evaluation depending on the progression of the disease.5

References

1. Buzzetti, E., Pinzani, M., & Tsochatzis, E. A. (2016). The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism: Clinical and Experimental, 65(8), 1038–1048.

2. Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016). Global epidemiology of nonalcoholic fatty liver disease—Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology, 64(1), 73–84.

3. Bacon, B. R., Farahvash, M. J., Janney, C. G., & Neuschwander-Tetri, B. A. (1994). Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology, 107(4), 1103–1109.

4. Neuschwander-Tetri, B. A. (2017). Non-alcoholic fatty liver disease. BMC Medicine, 15(1), 1–6.

5. Rinella, M. E. (2015). Nonalcoholic fatty liver disease a systematic review. JAMA – Journal of the American Medical Association, 313(22), 2263–2273.

6. Noverr, M. C., & Huffnagle, G. B. (2004). Does the microbiota regulate immune responses outside the gut? Trends in Microbiology, 12(12), 562–568.

7. Rivera, C. A., Adegboyega, P., van Rooijen, N., Tagalicud, A., Allman, M., & Wallace, M. (2007). Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis. Journal of Hepatology, 47(4), 571–579.

8. Jiang, W., Wu, N., Wang, X., Chi, Y., Zhang, Y., Qiu, X., … Liu, Y. (2015). Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease. Scientific Reports, 5, 1–7.