NON-INVASIVE TESTING
Once a person is diagnosed with fatty liver (or MASLD or NAFLD), the next step is to assess the risk of the condition advancing to advanced liver disease. This is typically done by determining the current fibrosis stage (ranging from F0, no fibrosis, to F4, cirrhosis).
Historically, liver biopsy has been the preferred method of staging liver disease. A liver biopsy involves removing a small slice of the liver from the patient for the purpose of diagnosing and staging potential liver diseae. A pathologist then reviews that sample under a microscope. A liver biopsy is typically performed in a hospital and requires a few hours of recovery after the procedure.
Recently, though, Non-Invasive Tests (NITs) have been increasingly used in that process. This will vary from physician to physician, based on each individual doctor’s experience and comfort level.
Here’s a broad comparison of Biopsy and NITs:
NITs are unlikely to replace liver biopsies completely. These tests may yield indeterminate results that often must be followed up by biopsy and, at least right now, biopsy is often required for clinical trials. The scientific community has done much work to validate the results of NITs compared to liver biopsy, which is expected to accelerate the use of NITs in clinical practice.
Hopefully, the information presented on this webpage will lead to informed discussions with your physician. The NITs can be used for both disease diagnosis and disease monitoring and fall into two general categories: 1) blood or serum testing and 2) imaging technologies. A hybrid category is also evolving, where blood tests are combined with imaging to forecast the likelihood of advanced liver disease. Much work is also being done using blood tests combined with proprietary algorithms.
Blood Testing
Blood tests are the most accessible of the NITs as the primary care physician can generally order them and do not require
the physician to invest in expensive equipment.
The Hepatic Panel (or Liver Function test) is the most commonly ordered blood test for assessing liver health. Many people at risk for advanced liver disease, however, have normal liver enzymes. However, the blood markers from this panel are useful in other assessments. The FIB-4 index (described in the Glossary) uses blood markers from the Hepatic Panel to assess the possibility of advanced liver disease and is currently the recommended blood test for the initial evaluation of liver health. Other blood tests that a physician may use include NIS-4, the Enhanced Liver Fibrosis (ELF) test, the OWLiver test and Liver Fast. These tests are described in the Glossary.
Imaging Technologies
These technologies are of two basic types. The first is a variation of an ultrasound.
The most common NITs of this type are categorized as Vibration-Controlled Transient Elastography (VCTE). Fibroscan was the first of the VCTEs and is probably the most commonly used. Fibroscan has competitors, though, including Velacur, Mindray, and Hepatoscope. The VCTEs are less expensive than other imaging technologies and often have portable applications. allowing them to be used at screening events outside a physician’s office. They still require a sizable capital investment by the practice or clinic. It would be unusual for a physician to have a variety of VCTEs in their clinic. Primary care physicians rarely have VCTEs available to them, and even some specialists may not have easy access. This makes the VCTEs less accessible than blood tests. In addition, these tests require trained personnel to interpret the test results.
The other imaging tests are variations of a magnetic resonance imaging test (MRI). The MRI – Protein Density Fat Fraction (MRI-PDFF) and the Magnetic Resonance Elastography test (MRE) are the two most common tests. The MRI-PDFF measures the amount of fat in the liver, which is highly predictive of disease progression. The MRE combines MRI imaging with low-frequency vibrations to measure liver stiffness. The MRI-PDFF and MRE are done in a hospital or specialty clinic setting, and a radiologist must interpret the results. These tests are more expensive than the other NITs and less convenient as they are not done in a physician’s office. These tests are generally more accurate than the other NITs.
It should be noted NITs are often used in combination with each other as liver disease severity is often difficult to assess. That is a Fibroscan may be followed by an MRI-PDFF or MRE. NITs have limited usefulness in the pediatric population, so this is largely an “adults only” discussion. While FIB-4 is not useful in children, some pediatricians have used VCTE with younger patients.
The following chart reflects the typical use of NITs in the staging process. Please note that in certain cases (e.g., a patient with type 2 diabetes), the testing will bypass the FIB-4 and proceed directly to ELF or VCTE.
GLOSSARY
ADAPT. A PRO-C3-based fibrosis algorithm that includes age, presence of diabetes, PRO-C3, and platelet count.
ALT (Alanine transaminase). Measures the amount of ALT in your blood. ALT levels in your blood can increase when your liver is damaged.
APRI (AST to Platelet Ratio Index). Calculates a score based on AST and platelet levels. AST to Platelet Ratio Index (APRI) (mdcalc.com)
AST (Aspartate Aminotransferase). Measures the level of AST and helps determine liver function. Too much of this enzyme can indicate a problem, such as liver damage.
ELF test (Enhanced Liver Fibrosis test). A blood test that uses three biomarkers (HA, PIINP and TIMP-1) in combination with a proprietary algorithm. ELF is used to identify the risk of progression to cirrhosis as well as the development of liver-related
clinical events. Approved by FDA.
FAST Score. Combines Fibroscan and the AST biomarker to identify patients at risk for advanced liver
disease.
FIB-4. Uses readily available blood markers (AST, ALT, and platelet count) plus the patient’s age to calculate an index score. The index can be calculated on line at https://www.mdcalc.com/calc/2200/fibrosis-4-fib-4-index-liver-fibrosis The
index uses three categories to assess risk as follows:
· Low risk for advanced liver fibrosis (index value less than 1.3)
· Intermediate risk for advanced liver fibrosis (index value from 1.3 to 2.6)
· Advanced risk for advanced liver fibrosis (index value greater than 2.6)
This index is most reliable in patients between the ages of 35 and 65.
Fibroscan. An ultrasound device that measures liver fat and scarring. A score is produced to assess liver
health.
Hepatic Panel. Blood tests that typically include albumin, ALT, AST, and ALP measurements. Bilirubin and
Prothrombin time). This test measures liver enzymes and markers of liver function. It should be noted that test results can be normal even with advanced liver disease.
Hepatoscope. A portable device that provides all ultrasound tools need for non-invasive assessment of liver health.
LIVERFASt. A blood-based diagnostic test 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 to produce
fibrosis and activity scores.
Liver Multiscan. Uses MRI technology to characterize liver tissue quantitatively. This technology assesses the entire liver and
provides information regarding the amount of liver fat, inflammation, disease activity, and iron content.
MASEF. A blood serum test includes 12 lipids, BMI, AST, and ALT to develop a score for identifying patients at risk for advanced liver disease.
MAST. Uses MRI-PDFF, MRE, and AST values to produce a score to identify fibrosis.
MEFIB. This measure combines MRE with the FIB-4 score to produce an index for identifying at-risk patients.
Mindray. A product using VCTE technology to assess liver health. It incorporates a 2D ultrasound image for staging and surveillance of liver health.
MRE. Combines MRI imaging with low-frequency vibrations to create a visual map that shows liver stiffness.
MRI (Magnetic Resonance Imaging). A test that uses powerful magnets, radio waves, and a computer to make detailed internal body images. It can be used for fatty liver and changes in liver shape, size, and surface nodularity. It does not typically
detect NASH/MASH or early-stage fibrosis but is excellent in monitoring patients with cirrhosis to detect liver cancer.
MRI – PDFF (Protein Density Fat Fraction). Uses MRI technology to measure water and fat in a tissue. The
amount of fat in the liver is highly predictive of liver disease progression. MRI-PDFF has the highest diagnostic accuracy for quantifying liver fat content of all the imaging tests.
NASH Fibrosis Score. Calculates a score based on glucose, platelet count, albumin and AST/ALT ratio. It can be
calculated online.
NASH Fibrosure. A blood test that uses the results of 10 biomarkers (a2-macroglobulin, haptoglobin, apolipoprotein A1, ALT, AST, GGT, glucose, cholesterol, and triglycerides in combination with a patient’s age and gender to calculate a score that measures
fibrosis and liver fat.
NIS-4. A blood test that utilizes four biomarkers (miR-34a-5p, YKL-40, alpha2-macroglobulin, and HbA1c1) combined with
a proprietary algorithm.
OWLIVER. A blood test based on metabolomic technology that determines liver activity by evaluating 28 biomarkers (metabolites) from a blood sample.
Pro-C3. Detects the formation of type lll collagen and can be measured with a blood test. Type lll collagen is one of the
most abundant proteins in fibrotic tissue and a reliable biomarker for liver fibrosis
Ultrasound. Uses sound waves with frequencies higher than the upper audible limit of human hearing. Provides
the ability to detect a swollen liver but does not measure scarring.
Velacur. An AI guided 3D S-WAVE ultrasound elastography device that measures liver stiffness and attenuation, the two key
indicators of fatty liver disease
Vibration-Controlled Transient Elastography (VCTE). Assesses liver stiffness by capturing and calculating the speed of a shear wave as it travels through the liver.