NASH/NAFLD: Screening and Diagnostic Testing

The screening practice for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) depends on highly variable global guidelines. Screening refers to checking for a disease in the absence of symptoms. Early detection through screening increases the likelihood of successfully treating the disease. In the US, high-risk populations for NAFLD/NASH are screened through laboratory tests, imaging, and, sometimes, a liver biopsy to determine if they meet the criteria to be diagnosed with NAFLD or NASH.

Who is screened for NAFLD/NASH?

The American Association for the Study of Liver Diseases recommends targeted screening of high-risk populations, including those with type 2 diabetes mellitus, obesity with metabolic complications, a family history of cirrhosis, or significant alcohol use.

How is NAFLD/NASH diagnosed?

The following criteria must be fulfilled to establish a diagnosis of NAFLD and NASH:

• Fat buildup in the liver (NAFLD) and liver inflammation and scarring (NASH) should be found by using imaging tools such as ultrasound or through invasive procedures such as liver biopsy. A biopsy involves extracting a piece of the liver tissue to run tests on in a laboratory.
• For diagnosis, it is vital to confirm the exclusion of other causes of liver damage, such as alcohol use, metabolic comorbidities, chronic liver conditions, and other less common genetic conditions.

During a screening, to find out if you meet these criteria, your healthcare professional may perform the following:

• A medical history review
  • You will be asked questions about your health conditions, diet, lifestyle, and alcohol and medication use.
• A physical exam
  • A healthcare professional will examine your body and check for signs of NAFLD and NASH, such as enlarged liver or spleen, yellowing of the skin, and whites of your eyes. Your weight and height will be measured and used to calculate your body mass index (BMI).
• Additional tests
  • Blood tests
  • Imaging tests
  • Liver biopsy

What tests do doctors use to diagnose NAFLD and NASH?

No single test can be used to diagnose NAFLD or NASH. The diagnosis is established through a combination of the following tests:

Blood tests

Your doctor may request the following laboratory tests to detect, evaluate, and monitor liver disease and damage:

• Liver function tests (LFTs) or liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
• Lipid profile, including cholesterol and triglycerides
• Hemoglobin A1C and ferritin
• Fibrosis assessment tests, including AST-to-Platelet Ratio Index (APRI) score and Fibrosis-4 (Fib-4) score
• Tests for viral hepatitis, including hepatitis C, A, and B
• Tests for rare genetic conditions such as Wilson's Disease

For a blood test, a healthcare professional will insert a needle into your vein and take a blood sample. The sample will be sent to a lab for further analysis.

Routine blood tests are used to examine the functional state of your liver and the presence of metabolic abnormalities, as well as to calculate special scores such as APRI and FIB-4 in order to evaluate scarring.

Blood tests for hepatitis and other liver conditions are used to exclude the presence of these diseases.

Increased ALT and AST levels suggest liver inflammation. However, these enzymes do not reveal the extent of scarring and liver damage.

Imaging tests

Imaging tests include the use of imaging devices such as ultrasound to take pictures of your liver. Some of them will require a special chemical (contrast) that will help take a better image of your liver. The following tests may be used to diagnose NAFLD or NASH:

• Ultrasound
• Computed tomography scan (CT)
• Magnetic resonance imaging (MRI)
• Transient elastography (TE)
• Magnetic resonance elastography (MRE)

Routine imaging studies such as ultrasound, CT, and MRI show fat buildup in your liver but cannot tell if you have inflammation or scarring. In cases of serious liver damage, these tests may show nodules, or lumps, in your liver.

Modern imaging studies such as TE and MRE measure the stiffness of your liver caused by scarring and show the extent of liver damage.

Liver biopsy

A liver biopsy is the gold standard test for telling apart NASH from NAFLD. It is an invasive procedure recommended only if your other test results suggest more serious liver disease.

During the procedure, a healthcare professional will place a needle between your ribs into your liver and take small pieces of liver tissue. A pathologist will examine this tissue sample under a microscope for any signs of liver damage. Liver biopsy results showing fat deposition but no inflammation or cell damage suggest a NAFLD diagnosis. If fat is found along with inflammation and cell damage, your doctor will establish the diagnosis of NASH.

Do you need to prepare for testing?

Some tests may require little to no preparation. For other tests, such as certain blood measurements, imaging studies, and liver biopsy, you will be asked to fast (avoid drinking or eating), stop taking certain medications and supplements, and avoid strenuous physical activity.

Make sure to discuss the exact preparation steps with your healthcare professional and follow all the guidelines.