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Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A global healthcare burden

What is NAFLD and NASH?

Nonalcoholic fatty liver disease (NAFLD) is a group of conditions that is characterized by the accumulation of excess fat in the liver that is not directly attributed to the consumption of alcohol. While it is normal for the liver to contain small amounts of fat, if 5-10% of the liver’s weight is fat, it is considered a fatty liver or steatosis.1 If left unmanaged, some individuals may develop a more severe form of NAFLD known as nonalcoholic steatohepatitis (NASH), which can lead to liver scarring, cirrhosis, end-stage liver failure and hepatocellular carcinoma (HCC).

 

NAFLD commonly occurs in patients who are overweight, diabetic, or have high cholesterol and triglyceride levels. It is the most widespread form of chronic liver disease in the U.S. and affects up to 100 million people. Reports show that there are significant racial and ethnic disparities associated with NAFLD prevalence and severity in the U.S, with the highest burden found in Hispanics.3 Globally, the prevalence of NAFLD in the general population is estimated to be 25%.4

 

Symptoms and risk factors of NAFLD

During the early stages there may be no apparent symptom onset. However, some patients may experience several symptoms including:

fatigue

Fatigue and weakness

weight loss

Weight loss

stomach pain

Abdominal pain

swollen_legs

Swelling in legs and abdomen

While obesity, diabetes, high cholesterol and triglycerides are common factors that can lead to NAFLD, there are other risks associated with the disease:5,6

 

  • High blood pressure
  • Obstructive sleep apnea

  • Polycystic ovarian syndrome (PCOS)

  • Hepatitis C (HCV) infection

  • Underactive thyroid (hypothyroidism)

  • Underactive pituitary gland (hypopituitarism)

  • Metabolic syndrome

 Four main stages of NAFLD progression:1,7

1. Simple fatty liver (steatosis)

This is the earliest stage of NAFLD with a small amount of liver fat build-up. Considering a large percentage of the world is estimated to have NAFLD, individuals at this phase may not experience any symptoms.

middle east

31% of the population

The highest prevalence of NAFLD is in the Middle East4
 
South America

30% of the population

The second highest prevelance is in South America4
Africa

13% of the population

Lowest prevalence is in Africa4
2. NASH

NASH is the serious form of NAFLD where the liver becomes inflamed, starts to swell and becomes damaged. Typically found in people 40 to 60 years old, NASH occurs when there is 5% or more hepatic steatosis and inflammation with hepatocyte injury, and can include fibrosis Liver biopsy is the gold standard for diagnosing NASH. To date, there is no set regimen for treatment outside of lifestyle changes.

59%

is the estimated prevalence of NASH in patients already with NAFLD8

3-5%

of the general population is affected by NASH globally9

40-60 year olds

is the typical age when NASH occurs
3. Fibrosis

At this stage, scar tissue begins to develop in the liver and around blood vessels through collagen and protein build-up between liver cells as chronic inflammation continues. This can restrict blood flow to the liver. During fibrosis, patients still may not experience symptoms, depending on the stage of fibrosis, since the liver can still function and early stage fibrosis is reversible.

4. Cirrhosis

Cirrhosis is the most severe stage.  Cirrhosis can lead to abdomen fluid buildup, vein swelling in the esophagus, hepatic encephalopathy, liver cancer and end-stage liver failure. At this stage, liver transplantation may be required.6 

 

>50 years old

is the typical age when cirrhosis occurs

5-12%

estimated of NASH patients will develop cirrhosis
Detection of NAFLD and NASH

It can be difficult for patients to determine if they have NAFLD because in most cases, symptoms are not evident. There are several methods, both non-invasive and invasive, that healthcare providers can use to diagnose NAFLD and NASH.

blood-tests

Blood tests

 

To determine liver function, physicians may order blood tests to detect liver disease. More specially, liver enzymes ALT (alanine aminotransferase) and AST (aspartate aminotransferase) will leak into the bloodstream due to damaged or destroyed liver cells.

Additionally, fibrosis can be detected using the blood tests AST-to-Platelet Ratio Index (APRI) score and Fibrosis-4 (Fib-4) score to estimate the level of liver scarring.

 

Imaging

Imaging technologies can be used to help diagnose NAFLD as well as measure fibrosis by examining liver stiffness. Some typical imaging examples include ultrasound, CT scan and MRI. While ultrasound and CT may be limited in diagnosis in certain cases, both are sensitive to diagnosing moderate to severe hepatic steatosis. MRI methods are accurate for hepatic fat measurement. To detect stiffness and fibrosis, transient elastography or magnetic resonance elastography can be used.

 

Liver biopsy

 

Liver biopsy is the gold standard for detecting liver disease, especially NASH. While blood tests and imaging are useful methods to detect liver status, liver biopsy is a definitive technique for accurate diagnosis. A small sample of liver tissue is taken for lab testing to determine fat deposits, scarring, inflammation and liver cell damage. In NASH, some biopsy characteristics include mild to moderate iron deposits in hepatocytes, Kupffer cells and fibrotic sinusoidal endothelial cells.11 While liver biopsy is considered the best diagnostic, imaging techniques still have important advantages, particularly in cancers, and have advanced to the point where cirrhotic liver tumors can be accurately identified.

 

biopsy-scientists
exercise

Reducing the Risk

 

With NAFLD such a prevalent disorder worldwide, there are several lifestyle modifications that can be incorporated to reduce the risk and to prevent more severe liver disease, which can ultimately lead to liver failure or cancer.1,6

 

  • Eat a healthy diet

  • Maintain a healthy weight

  • Exercise regularly

  • Limit alcohol intake

 

As the most common chronic liver condition in the U.S. and the high prevalence worldwide, NASH can quickly lead to more serious liver complications. By gaining a better understanding of disease progression and long-term consequences, patients can work with their healthcare providers, families and support groups to determine which treatments or lifestyle modifications are most suitable. Becoming better informed early can help patients improve their well-being and quality of life, and reduce the risk of developing a more serious condition.

 

References

  1. https://liverfoundation.org/for-patients/about-the-liver/diseases-of-the-liver/non-alcoholic-fatty-liver-disease/. Accessed April 2021.
  2. American Liver Foundation. https://liverfoundation.org/for-patients/about-the-liver/diseases-of-the-liver/non-alcoholic-fatty-liver-disease/#facts-at-a-glance. Accessed 30April2021
  3. Rich NE et al. Clin Gastroenterol Hepatol. 2018 Feb; 16(2): 198–210.e2.
  4. Younossi Z et al. Hepatology. 2019 Jun;69(6):2672-2682.
  5. https://liverfoundation.org/for-patients/about-the-liver/diseases-of-the-liver/nonalcoholic-steatohepatitis-information-center/nash-causes-risk-factors/. Accessed April 2021.
  6. https://www.mayoclinic.org/diseases-conditions/nonalcoholic-fatty-liver-disease/symptoms-causes/syc-20354567. Accessed April 2021.
  7. https://www.nhs.uk/conditions/non-alcoholic-fatty-liver-disease/. Accessed April 2021.
  8. Chalasani N et al. Hepatology. 2018 Jan;67(1):328-357.
  9. Younossi ZM. J Hepatol. 2019 Mar;70(3):531-544. 
  10. https://liverfoundation.org/for-patients/about-the-liver/diseases-of-the-liver/nonalcoholic-steatohepatitis-information-center/nash-diagnosis/. Accessed April 2021. 
  11. Madrazo BL. Gastroenterol Hepatol (N Y). 2017 Jun; 13(6): 378–380.