Division of Gastroenterology and Hepatology
Saint Louis University School of Medicine
The American Association for the Study of Liver Diseases released an updated practice guidance on nonalcoholic fatty liver disease (now called metabolic dysfunction–associated steatotic liver disease [MASLD]) in January (Hepatology 2023;77:1797-1835). GEN’s Sarah Tilyou spoke with co-senior author Brent A. Neuschwander-Tetri, MD, a professor of internal medicine in the Division of Gastroenterology and Hepatology at Saint Louis University School of Medicine, about the guidance and its implications for GI practice.
GEN: What prompted the practice guidance?
Dr. Tetri: For MASLD, we’re seeing a lot of advances in clinical trials, especially in noninvasive testing. The guideline is meant to educate clinicians about how to use this testing in our clinical practices to risk-stratify our patients and determine who is at risk for progressing to cirrhosis and its complications. Those are the people we really need to identify and focus our efforts on.
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GEN: What’s new in the guidance that clinicians need to know?
Dr. Tetri: This guidance has a nice algorithm for how to handle patients with steatotic liver disease. The guidance suggests that we do some initial risk assessment for advanced disease, and this focuses on the Fibrosis-4 score (FIB-4). FIB-4 has strengths and weaknesses, but the biggest strength is that it is so readily available based on routine labs. Many healthcare systems—mine included—might have it automatically calculated from labs, so it’s really easy to do, with little cost or time added to a clinic visit.
The numbers from the FIB-4 can give us comfort or give us concern. If the FIB-4 is below 1, we’re very comfortable—that patient is unlikely to develop complications. If it’s under 1.3, we’re still comfortable enough that we don’t necessarily need to do additional testing, but we do need to keep a close eye on patients with metabolic disease. For those in the intermediate zone of 1.3 to 2.67, we should do some additional testing, and if it’s over 2.67, we really have to find out what’s going on, with additional testing such as magnetic resonance elastography and possible biopsy.
For that intermediate zone, we can often do other testing, which would include vibration-controlled transient elastography (FibroScan, Echosens) or other types of elastography or blood tests such as the enhanced liver fibrosis (ELF) score—although the ELF score, which is often not covered by insurance, is used more in Europe.
This will continue to evolve. These tests we’re recommending aren’t perfect, and we will continue to get better tests. The overall point is that we should do something and not just ignore these patients. That’s the message for GI providers, and also for endocrinology providers caring for patients with type 2 diabetes. This guidance is very similar to what is in the diabetes guidance statements and also the European Association for the Study of the Liver guidance statements. That’s intentional. We want to have a clear message for providers, underscoring that they should be doing something for risk stratification. We also want to provide some guidance on when patients should be referred out of primary care or endocrinology practices to GI practices and hepatologists.
GEN: How might the new guidance change practice?
Dr. Tetri: We sure hope it changes practice because there’s a lot of people out there who are not followed at all or are followed by primary care and aren’t getting evaluated appropriately. For example, a patient has a platelet count that’s been a little bit on the low side and their liver enzymes have been up a little bit, but they are told, “You just have fatty liver, don’t worry.” Then, they come to us when they’re cirrhotic, very frustrated, saying somebody should have looked at this sooner. We need to continue to get the word out to primary care, endocrinology and whoever else will listen that we can’t ignore this.
GEN: What were some of the hottest points of debate among the guidance panel and how did you resolve them?
Dr. Tetri: Selecting the FIB-4 as that first noninvasive test to consider was a point of debate. Like I said, it has its strengths and it has its weaknesses—it’s not perfect. Should we have chosen something else? Ultimately, we chose it just for the practicality of it. There was a lot of debate around that as well as about what the thresholds should be. Should we have chosen a lower FIB-4 number? The lower the number we suggest for referral, the higher the number of referrals of patients without significant risk for progression. Too low a number overburdens the GI and hepatology practices. But granted, we’re going to miss patients setting it at 1.3—it’s a trade-off.
GEN: What are the biggest remaining gaps in evidence?
Dr. Tetri: Ultimately, we need better noninvasive testing. There are a lot of things being worked on, and this field will continue to evolve. We’re starting to get hints at some very novel things out of proteomics and lipidomics studies, and we might see tests emerge in the next three to five years based on blood proteins we don’t even talk about right now that represent fibrosis or steatohepatitis. So that’s a huge gap.
And then, of course, treatment. We’re starting to get a lot of exciting results out of phase 2 and phase 3 studies. I think in the next five to 10 years, we will see the emergence of a lot of treatment options.
But that creates another huge gap that we just don’t talk about that much, and that’s getting into an era of precision medicine or personalized medicine. All the trials of these new therapies that are looking pretty good, they don’t work in everybody. So, can we do genetic tests, can we do other things, such as blood tests, to identify who’s going to respond to, for example, resmetirom, which may be approved this year for MASH? If we could know by blood tests or genetic tests that a patient is not going to respond to a particular treatment, we’ll know not to start them on that therapy. It would be great to have a panel of tests that identify the appropriate treatment for a given patient.
GEN: What’s the take-home message for GI clinicians?
Dr. Tetri: The core message is that we should take MASLD very seriously as a major cause of chronic liver disease and listing for liver transplantation. We need to be on the lookout for patients with MASLD and identify them. Even though we don’t have approved pharmacotherapy, there is such good evidence that lifestyle modification does make a difference. Healthy eating, a little bit of weight loss can really put the brakes on this disease. I think that’s a positive message we need to continue to get out there. Even when we have approved pharmacotherapies, lifestyle modification still will be the foundation for all therapies. I think nobody would argue that it’s OK to let people just eat all the junk food they want, sit around and watch TV all day, and take a pill to make their liver better.
It’s always a challenge to get patients to adopt healthier lifestyles, but there are a lot of tools out there to deal with it. I teach patients about this as much as I can. I often tell my patients that many common fast food meals have as much fat in them as a stick of butter (92 g). It’s incredible, but people don’t realize it. I emphasize a Mediterranean diet, limiting simple carbs, using healthier oils, minimizing fat overall. Also, I always recommend eliminating sugar-sweetened beverages, and I tell my patients that the liver converts that sugar into fat, which adds to the damage in the liver. And I stress the benefits of regular exercise. These changes can make a big difference.
This article is from the March 2024 print issue.