By definition, NASH or nonalcoholic steatohepatitis is a form of fatty liver disease. NASH may be a result of a metabolic disorder such as diabetes or obesity that develops from the toxins that build up in the liver. NASH is a severe form of nonalcoholic fatty liver disease.
A recent article in Medical Technology reports that NASH is difficult to diagnose as its symptoms are usually not detectable. Therefore patients may not be aware of having the disease until it is in the late stages.
Most people are not significantly affected but others will experience liver cell toxicity causing cell damage and inflammation.
Currently, three types of non-invasive NASH tests are being used, albeit not with the highest degree of accuracy.
The first group of tests results in a score using a clinical algorithm including the patient’s medical records. An example of this type of test is an FIB-4 test. It uses the patient’s age, platelet count, ALT, and AST levels.
However, Sven Francque, M.D. commented that this test is more relatable at the population level as it fluctuates by day and technician.
The second group of noninvasive tests is radiologic tests measuring the liver’s stiffness. For instance, elastography can measure liver stiffness as it corresponds to fibrosis at a particular stage. Yet Dr. Francque points out that since liver stiffness does not qualify as fibrosis, it can be affected by elements such as nutritional status.
Dr. Francque explains that liver fat should not be considered a primary measure in NASH. Instead, ballooning and liver inflammation should be considered.
The third group using noninvasive testing is serum-based such as the Enhanced Liver Fibrosis (ELF) test. Although ELF tests offer simplicity, it is difficult to get payors to cover the cost.
ELF tests have a history of being used in Asia and Europe but they only recently arrived in the U.S. Therefore efforts should be put forth to raise awareness.
The authors of the study suggest that the best approach would be a process starting with FIB-4, followed by elastography or ELF. It is believed that by following this process both negative and positive predictive values will be optimized that would either exclude or include cirrhosis.
The authors suggested that possibly four to five invasive tests may be needed to provide a more complete picture of progress and disease status. Anything less may bring about inaccuracy.
Outside the three groups, there are still other tests that deliver advantages to functional testing. This method of testing measures the functioning of the liver before there are any noticeable changes in fibrosis. It is noteworthy that the drugs that are given regulatory support are the drugs that improve outcomes without scarring.
One functional test focuses on substrates called C-13. The liver becomes healthier if the substrate can be broken down early. But on the negative side, there are factors such as intestinal absorption which can impact data.
The last item on the list is a liver biopsy. This test has several issues such as pain and bleeding. Placement of the biopsy needle can bring about either a positive or negative result.
These factors pertaining to a liver biopsy can determine varied outcomes. The other factor that cannot be ignored is the significant cost.
One last item on the ‘functional’ list under investigation is a breath test. There are many questions in this regard, especially when these tests are compared to blood tests.
About Artificial Intelligence (AI)
Researchers are considering artificial intelligence as a substitute for the variability occurring in pathologists’ reports. AI’s main advantage is standardizing analysis. AI is better equipped to authenticate whether a change in the biopsy of a patient is accurate.
For the time being, biopsies will continue as Phase III clinical trial primary endpoints. The FDA prefers a drug that not only improves organ function but also an improvement in quality of life. The researchers feel that this is over and above what a biopsy can deliver. Although they have a huge amount of data, a simple method of extracting this data has not yet been devised.
If accepted by the FDA however, the company will have to report reduced complications caused by the disease and improvement in overall length of life.
Noninvasive tests can analyze the fibrosis state of an individual’s liver. Fibrosis evaluates the state of an individual’s liver as well as monitors the progression of their disease. But none of these tests can be used to reliability monitor patients. There is also the need to identify the best outcome data to determine the optimum test combination.
Doctors Dufour and Younossi both weighed in on the present state of NASH diagnostic tools, agreeing that fibrosis is the key and that it predicts mortality.
FIB-4 is the initial step and can be used to diagnose patients they suspect as having NASH.