Historically, we used liver biopsies, but a huge amount of work has been done in recent years with noninvasive tests that allow us to prognosticate. The Enhanced Liver Fibrosis (ELF) test (Siemens Healthineers) is already approved by the US Food and Drug Administration as a prognostic biomarker, and it is particularly useful in identifying patients with increased risk of nonalcoholic steatohepatitis who would require aggressive treatment.

The Fibrosis-4 (FIB-4) index is a simple tool, but it has great negative predictive value. And if you consider a patient with a FIB-4  that is under 1.3, their risk of dying from liver disease is very low. If the FIB-4 score is above 2.67, their risk of dying from liver disease increases. So, for practicing clinicians, key prognostic tools include the FIB-4, liver stiffness measurements (calculated by FibroScan [Echosens]), and magnetic resonance elastography (MRE) as a backup tool.

I would encourage clinicians to use the patient’s FIB-4 score as a starting point. In cases of diagnostic uncertainty and/or when there is a strong family history of liver disease, we should keep investigating. FibroScan is among the most widely used tools in clinical practice. Like the FIB-4, FibroScan has very good rule-out value. It also provides a continuous attenuation parameter, which gives a semi-quantitative measure of liver fat, providing both diagnostic and prognostic information.

There are many other biomarkers that are in development, and the use of noninvasive tests is likely to evolve over time. However, at present, I would encourage clinicians to start by looking at the FIB-4, to use the liver stiffness measurements by FibroScan as a secondary tool, and then to use MRE to help ascertain complex cases in which there is a lack of diagnostic clarity.

Thinking specifically about patients who fall in the indeterminate zone after the initial screening, I use several different approaches. Decisions are made in consultation with the patient, after reviewing all of the options and their pros and cons. If I think that the patient is very motivated, I may recommend lifestyle changes and bring the patient back for reassessment in 6 to 12 months.

When a liver biopsy is warranted, we recommend having the procedure if the patient is willing. If the patient does not want to have a biopsy, then we can perform either an ELF test or an MRE scan. The use of MRE may be dependent on the availability of equipment, expertise, and other factors, including contraindications, a patient’s unwillingness to undergo the procedure, and insurance approval.

Thus, there are many options for risk stratification, including observation and retesting. Although there are rapid progressors, NAFLD is a slowly progressive disease for the most part, in contrast to alcohol-associated liver disease. If a patient is motivated to implement lifestyle changes, such as diet and exercise, you can reassess them after 6 to 12 months. Further, if the patient has lost weight, repeating the biochemical tests can be useful in deciding which patients can be followed by their primary care providers and which patients should continue to be followed by hepatologists.

We have seen that having a care pathway or a process for assessing the severity of NAFLD is key. For the clinician who encounters these patients in their practice, it is important to apply some form of stratification to aid in the routine assessment of these patients. The FIB-4 and liver stiffness measurements are great ways to start; these tests can then be used to guide referrals to specialty care. Liver biopsy has been the gold standard for some time, but emerging data on noninvasive tests, which appear to be robust, should enable us to incorporate these tools into primary clinical practice and to make them a part of the standard of care in the assessment of persons with NAFLD.

Unfortunately, there is a gap between the current guidelines and the use of noninvasive risk stratification tools in clinical practice. In the real world, these tools are not being used consistently. Nonetheless, this translates into an opportunity for academic entities and organizations to generate guidance documents that are easily read, understood, and implemented by health care practitioners. There is an unmet need for specialties such as hepatology and gastroenterology to interact with and develop these practice guidelines in conjunction with family practice, internal medicine, and medical weight loss practices, since the average diabetologist or family practitioner may have a limited appreciation of hepatology or gastroenterology practice guidelines.