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The diagnosis and monitoring of liver disease can be confusing to patients. While most of us have heard of liver biopsies, not everyone knows about the variety of NITs that are currently in use.

While long considered the gold standard for diagnosing liver disease, invasive liver biopsy is an unpleasant procedures that carries its own set of risks. In addition, there are studies that indicate that a biopsy may be no more accurate than non-invasive tests. Our experience is that no one wants a liver biopsy. Here are some reasons why you might not want to have one:

  • A liver biopsy only looks at a tiny sliver of the liver; liver disease is not necessarily uniform throughout the liver so it may not actually depict overall liver health
  • May be useful for an initial diagnosis, but generally unsuitable for monitoring a condition over time
  • It can be painful
  • There is a risk of infection
  • Bleeding can result
  • The process is time consuming and requires someone to accompany the patient
  • There is variation in results interpretation

So why is it the gold standard? Well for one, the FDA requires a biopsy to measure endpoints in clinical trials. Hopefully, that will change over time as the evidence mounts regarding the usefulness and accuracy of NITs. Also, it is the only test that directly analyzes tissue samples. That does provide histological advantages

The purpose of this page is to provide an overall understanding from the patient perspective of the NITs that are presently in use and the circumstances in which they are presently used. This will facilitate informed discussions with your physician regarding the alternatives available for detecting and monitoring potential liver disease.

NITs have a large and growing role in the detection, staging and monitoring of liver disease. Their use is advised if you have any of the risk factors (diabetes, obesity, high blood pressure, etc.) associated with Nonalcoholic Fatty Liver Disease (NAFLD) or Nonalcoholic Steatohepatitis (NASH). The goal is to detect the presence of this disease and monitor its progression. Most people will not see their disease progress to a serious stage but any one at risk should monitor their liver health.

NITs fall into two general categories : 1) blood or serum testing or 2) imaging technologies. Generally, the blood tests is done initially for patients having any of the risk factors or experiencing symptoms. Our experience is that these tests are not done in the normal course of business and you may have to request them from your doctor. If this testing indicates a concern, the next step is to proceed to imaging. This usually begins with a referral to a specialist and the performance of an ultrasound. If problems are indicated the progression would then be to more sophisticated imaging technologies where the appearance and characteristics of the liver can be viewed by technicians and doctors.

The following tables provide general guidance on the use of the various forms of non-invasive testing. The first table describes serum, or blood, test. The second describes imaging tests.

Serum Tests

Type of TestWhat Is ItWhat It DoesWhen Is It UsedComments
AST to Platelet Ratio Index (APRI)Calculates a score based on AST and platelet levelsMeasures fibrosis.Early-stage screening tool for patients who may be at risk for NAFLD and/or NASHEasily calculated using readily available markers. Can be calculated using an on-line tool.
Enhanced Liver Fibrosis (ELF)Blood test that used three biomarkers (HA, PIIINP and TIMP-1) in combination with a proprietary algorithmCan be used in patients with advanced liver fibrosis due to NASH to identify risk of progression to cirrhosis as well as development of liver related clinical events.Allow for identification of those patients with a higher risk for serious outcomes. Used for risk stratification in those who are known to have NASH.Approved by the FDA. Has been used in Europe for a number of years and available in the US through LabCorp and Quest.
FIB-4FIB-4 is a scoring system determined from the values of patient age, platelet count, AST, ALTAids in diagnosis of advanced fibrosis. It is useful as a screening test or when used in combination with other tests with prognostic valuesEarly-stage screening tool for patients who may be at risk for NAFLD and/or NASH.Testing is very inexpensive and can be easily calculated using an online tool. FIB 4 is now part of the clinical care pathway recently put out by the AGA.
Hepatic PanelBlood tests which typically include measurements of albumin, ALT, AST, ALP, Bilirubin and Prothrombin time.Measures liver enzymes as well as markers of liver function and how well the liver is performing its normal function in producing protein and clearing bilirubin. No predictive value.Early-stage screening tool for patients who may be at risk for NAFLD and/or NASHTest results, though, do not always correlate with disease level. Tests can be normal even with advanced liver disease.
LiverFastBlood-based diagnostic tests that uses 10 biomarkers (Alpha-Macroglobulin, Haptoglobin
Apolipoprotein A1, total Bilirubin, GGT, ALT, AST, Glucose, Triglyceride and total Cholesterol)
in combination with a proprietary algorithm
Determines the fibrosis, activity and steatosis stages of the liverCan be used at all stages of liver care
NAFLD Fibrosis ScoreCalculates a score based on glucose, platelet count, albumin level and AST/ALT ratioUsed for detecting fibrosis in those with NAFLD.Early-stage screening tool for patients who may be at risk for NAFLD and/or NASHMakes use of readily available markers. Can be calculated using an on-line tool.
NASH FibrosureBlood test that uses the results of ten biomarkers (α2-macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, ALT, AST, GGT, glucose, cholesterol and triclycerides) in combination with a patient’s age and gender.Calculates a score that measures fibrosis and inflammation and steatosis (fat).Early-stage screening tool for patients who may be at risk for NAFLD and/or NASH.Probably the most frequently prescribed blood test aside from the Hepatic Panel.
NASHNext/NIS-4Blood test that utilizes four biomarkers (miR-34a-5p, YKL-40, alpha2-macroglobulin, and HbA1c1) in combination with a proprietary algorithmAssesses both NASH activity and fibrosis stage. Aids in the diagnosis of at-risk NASH or NASH with moderate liver fibrosisUsed for anyone with risk factors for NASHNASHNext is owned by Labcorp and powered by NIS4 technology

Imaging Tests

Type of TestWhat Is ItWhat It DoesWhen Is It UsedComments
UltrasoundSound waves with frequencies higher than the upper audible limit of human hearing2D grayscale image of the liver. Provides ability to detect swollen liver. Allows subjective estimation of liver fat. Does not measure scarring.Used when there is a strong suspicion of NASH. The liver fat assessment is a subjective determination. Must have at least 30% liver fat to be detected.Performed in a hospital or outpatient facility. Not particularly useful as a diagnostic tool other than to measure liver size and rule out lesions or diseases such as gallstones.
FibroscanAn ultrasound device that measures liver fat and scarring. A probe from the device is used to test the velocity of sound waves which provides a measurement of liver stiffness and liver fat.Produces a score used to assess liver health. Also used as part of a FAST score which combines liver stiffness, liver fat and blood results.Generally prescribed when there is an indication of liver damage. Good screening tool to identify at-risk patients. Limited predictive value.Generally performed in an office visit to a liver specialist or in a clinic. Obesity, inflammation and ascites may interfere with measurements. Variability in results must be considered. Can be used in children..
MRI (magnetic resonance imaging)A test that uses powerful magnets, radio waves and a computer to make detailed pictures inside your body.May be suitable for detecting fatty liver and some of the hallmark features of liver cirrhosis (such as changes in liver shape, size or surface nodularity among others). However, it cannot detect NASH or early stage liver fibrosis. Excellent for monitoring patients with cirrhosis to detect liver cancer.Provides information to be interpreted by a radiologist.Performed in a hospital or specialized MRI facility. Typically ordered by a specialist.
MRI – PDFF (Protein Density Fat Fraction)Uses MRI technology to measure water and fat in a tissue. Water and fat protons have different resonance frequencies and can be separated for measurement purposes.Measures the proportion of fat in the liver. The amount of fat has been shown to be highly predictive of NAFLD progression.Provides information to be interpreted by a radiologist and/or a specialist.Performed in a hospital or specialized MRI facility. Typically ordered by a specialist.
MRE (Magnetic resonance elastography)Combines MRI imaging with low-frequency vibrations to create a visual map that shows stiffness of body tissues.Assesses more of the liver than a Fibroscan. Detects advanced scarring (fibrosis) more accurately than the other methods described above.Provides information to be interpreted by a radiologist and/or a specialist.Performed in a hospital or specialized MRI facility. Typically ordered by a specialist.
Liver MultiscanUses advanced multi-parametric MRI-based technology to quantitatively characterize liver tissue, proving a comprehensive analysis that can aid in diagnosis, risk stratification and monitoring of liver disease.Provides complete information regarding the amount of liver fat, inflammation, disease activity and iron content. Assesses the entire liver.Provides information to be interpreted by a radiologist and a doctor. Reports are patient-friendly and intuitive.Performed in facilities with MRI capabilities. Typically ordered by a specialist. Utilizes MRI-PDFF as part of the analysis.