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Non-alcoholic fatty liver disease (NAFLD) is a collective term used to describe a group of conditions where there is an abnormal accumulation of fat in the liver in those who drink little to no alcohol. This may range from a non-serious condition called fatty liver to a potentially serious condition called non-alcoholic steatohepatitis or NASH.
The prevalence of NAFLD in the United States is reported to be between 10% and 30%, and the pooled overall global prevalence of NAFLD diagnosed by imaging was estimated to be greater than 25%. However, the exact prevalence of NAFLD and NASH in an adult population remains difficult to assess due to the lack of a cost-effective and widely available, minimally-invasive diagnostic test, and to the absence of specific symptoms before end-stages.
The liver is the largest solid organ in the body and it performs many essential functions, such as nutrient metabolism, protein synthesis, bile production, and glycogen storage. A healthy liver is blood-red with a smooth surface and contains 5% (or less) fat.
Fatty liver, or non-alcoholic hepatic steatosis, is observed in individuals who chronically consume excess calories and/or have a sedentary lifestyle, in the absence of significant alcohol consumption. Excess calories are stored in liver cells as lipids, resulting in a liver with fat content above 5% and a pale yellow color.
After enough excess fat has accumulated in the liver, chronic inflammation and cell death (ballooning) result in NASH. At this stage, patients have a higher risk of death from cardiovascular disease.
Chronic and continuous cell damage and ballooning result in the formation of fibrous scar tissue (fibrosis). Eventually, excessive scar formation will result in loss of liver function, a state known as cirrhosis or stage 4 fibrosis.
Patients with NASH-related cirrhosis are at higher risk of end-stage liver diseases, such as loss of liver function (decompensation), liver failure, and hepatocellular carcinoma (liver cancer). They are also at higher risk of death from cardiovascular disease and non-liver cancer.
Labcorp is on the cutting edge of NASH research, in both diagnostics and drug development. Learn more about what we're doing to help solve for this silent epidemic.
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Healthcare providers, whether primary care physicians or specialists, are on the front line in the fight against NASH. Labcorp offers information about symptoms, guidance and histology.
NASH is a chronic liver disease characterized by liver cell injury (hepatocellular ballooning) and inflammation as a result of fatty accumulation (steatosis) seen in at least 5% of hepatocytes.
This leads to liver scarring and the development of fibrosis (scored F0 to F4). As fibrosis worsens, liver-related morbidity (including cirrhosis and hepatocellular carcinoma) and mortality increase.
Contact a representative to learn more about how we can help meet your NASH and NAFLD testing needs.
A number of health organizations have issued guidance, guidelines and/or recommendations regarding the diagnosis of and treatments for NASH. The following documents are provided for informational purposes.
Dr. Connelly, the lead scientist behind Labcorp's NASH and NAFLD portfolio, discusses the clinical significance of NASH and what positive NASH and liver fibrosis test results mean for patients.
Histology is important in the evaluation of NAFLD. There have been three scoring systems for NAFLD in recent years, with the most recent being a semiquantitative scoring system validated by the National Institutes of Health–sponsored Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) in 2001. This system outlines the NAFLD activity score (NAS), a composite score of steatosis, lobular inflammation, cytological ballooning, and fibrosis (disease stage).
| Steatosis Grade | Fibrosis Score | ||
| Degree | Description (%) | 0 | None |
| 0 | <5 | 1a | Mild (delicate) zone 3 perisinusoidal fibrosis |
| 1 | 5-33 | 1b | Moderate (dense) zone 3 perisinusoidal fibrosis |
| 2 | 34-66 | 1c | Portal/periportal fibrosis only |
| 3 | >66 | 2 | Zone 3 perisinusoidal fibrosis with portal/periportal fibrosis |
| 3 | Bridging Fibrosis | ||
| 4 | Cirrhosis | ||
*NASH Clinical Research Network (CRN) Scoring System
Looking for research on NAFLD and NASH? Review the scientific papers and presentations about NAFLD and NASH that Labcorp has played a role in developing:
Labcorp Drug Development is the industry thought leader in NASH drug development. Its NASH Education Center provides additional NASH resources, including webinars, case studies and scientific articles related to NASH.
Many people have probably never heard of NASH. Learn about its origins, the terms to know, and how NASH relates to other lifestyle factors.
What is NASH? NASH is a form of fatty liver disease. According to researchers, one in four people is affected by fatty liver disease, which can develop for a number of reasons. There is good news, though. The effects of NASH can be reversible, mainly through lifestyle modifications. Changes such as eating healthier, increasing activity, and losing weight can improve or even reverse the effects of NASH. Knowing your risk is the first step to taking control of the disease.
One of the primary functions of the liver is to process fat; whether breaking down carbohydrates and proteins for use by the body, or synthesizing other fats, like cholesterol, either for use in the body or removal (think: bathroom).
But the liver isn’t meant to store fat. When there is too much buildup of fat in the liver (more than 5%), this is called steatosis. As a means to protect the liver, inflammation and scarring (or fibrosis) starts to occur, and can negatively impact the liver’s primary jobs if it continues to progress without intervention, mainly through lifestyle changes.
When this happens in someone who is not a heavy drinker, it is referred to as Non-Alcoholic Steatohepatitis, or NASH.
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If left unchecked, NASH can be deadly. In essence, there are three main stages of NASH:
stage 1
Fat in the liver exceeds 5% (steatosis), inflammation occurs, and the liver is bigger than normal. Typically in stage 1, the liver will continue to function as it normally would, but may be compromised. This is also referred to as Compensated Cirrhosis, or NASH without Fibrosis.
stage 2
In addition to stage 1 characteristics, scarring (fibrosis) begins to appear. Fibrosis can be classified as F1 through F4; Stage 2 of NASH involves fibrosis from F1 to F3. When a patient reaches this stage, the liver begins to deteriorate into liver failure. This is also referred to as NASH with Fibrosis.
stage 3
The most severe stage of NASH, the disease deteriorates into full-on cirrhosis or liver cancer. When this happens, the only option left is a liver transplant.
There are additional risks involved with a NASH diagnosis. The liver is at the center of the body’s metabolic processes, balancing out the body’s good and bad cholesterol – HDL and LDL, respectively. Damage to the liver as a result of NASH can release molecules into the bloodstream that can be harmful for the cardiovascular system.
NASH symptoms might not be immediately visible to people in the early stages of the disease. Most people who have NASH feel fine and probably don’t know they have it. As the disease progresses, however, and liver damage gets worse, they may start to see a worsening of symptoms, including:
Extreme tiredness
Unexplained weight loss
General weakness
Aching in the upper right part of the abdomen
It may take many years for NASH to become severe enough to cause symptoms.
No single test can diagnose NASH. Your doctor will ask you about other health problems you've had. To see if fat is building up in your liver and to rule out other diseases, your doctor may do tests such as:
Biopsy
Blood tests
An abdominal ultrasound
A CT scan
An MRI scan
In some instances, a physician might request a liver biopsy to help diagnose NASH.
Typically, most people who develop NASH are between 40 and 50 years old, and have one or more health concerns. On the other hand, it is possible for individuals with none of these risk factors to develop NASH.
There is no consensus as to why some patients develop NASH and others do not. While environmental factors and family genetic history are potential causes that could trigger the disease, there are still a lot of unknowns.
What science does agree on are the factors that can put people at risk for NASH and liver damage:
Obesity
Insulin resistance and type 2 diabetes
High cholesterol and high triglycerides
Metabolic syndrome
The best course of action is managing the conditions that can increase an individual’s risk for NASH, or exacerbate the disease. This includes:
Reducing total cholesterol levels
Maintaining a healthy weight. Some research has suggested that reducing as little as 3-10% of your total body weight can make a difference
Control diabetes
Stop or cut back on drinking alcohol
Exercise regularly
Type 2 diabetes influences the relationship between NAFLD/NASH and cardiovascular disease. According to research, NAFLD was found in 50% of patients with type 2 diabetes who had an otherwise healthy liver. In addition, NAFLD/NASH-related cardiovascular issues are nearly twice as likely in individuals with type 2 diabetes.
NAFLD/NASH and type 2 diabetes share many of the same risk factors: inactivity, obesity, genetics and environmental factors all add to the occurrence of these diseases. In addition, people with type 2 diabetes are at greater risk of advanced fibrosis, which is a major indicator of NASH.
While serious, the good news is that the same measures to help prevent and treat type 2 diabetes – eating healthier, exercise, weight management – can improve NAFLD and NASH prognosis.
Biopsy: a procedure where a sample of tissue is taken from the body to perform further diagnostic testing. In the case of NASH, that tissue is taken from a patient’s liver.
Cirrhosis: Also known as liver cirrhosis or hepatic cirrhosis, cirrhosis is a condition where the liver does not function properly due to long-term damage, typically characterized by the replacement of normal liver tissue by scar tissue.
Fatty liver disease: Fatty liver disease is a condition where excess fat builds up in the liver. Often there are no or few symptoms. There are two types of fatty liver disease: non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). NAFLD is made up of simple fatty liver and non-alcoholic steatohepatitis (NASH). The primary risks for fatty liver disease include alcohol, type 2 diabetes, and obesity.
Fibrosis: Also known as fibrotic scarring, fibrosis is a thickening of connective tissue in the body. It can occur as the result of normal healing, or due to excess tissue deposits. In the case of NAFLD and NASH, fibrosis is the result of the latter, also known as scarring.
Liver: The liver is an organ located at the upper right area of your abdomen. While it performs hundreds of functions in the body, its main jobs are: controlling blood sugar levels; filtering all materials (including foods, medicines, and alcohol) in the body; and processing fat.
NAFLD: Non-alcoholic fatty liver disease, or NAFLD, is a collective term used to describe a group of conditions where there is an abnormal accumulation of fat in the liver in those who drink little to no alcohol.
NASH: NASH stands for Non-Alcoholic Steatohepatitis. It is a liver disease from the family of NAFLD (non-alcoholic fatty liver disease).
Steatohepatitis: A type of fatty liver disease characterized by inflammation of the liver with coexisting fat accumulation in liver. This can occur due to prolonged alcohol intake, or other causes – in which case the disease is classified as ASH.
Steatosis: Also called fatty change, steatosis is abnormal retention of fat within a cell or organ. Steatosis most often affects the liver, where the condition is commonly referred to as fatty liver disease.
