Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of fatty liver disease. Estimates from the American Liver Association indicate that MASH affects between nine million and 15 million adults in the United States: a prevalence expected to make it the leading cause of liver transplantation in the years to come. This Q&A from our doctors at GastroIntestinal Specialists (GIS) helps to answer some common questions about MASH and explain more about our clinical trials.
1. What is MASH, and how is it different from “fatty liver disease” or NASH?
MASH stands for metabolic dysfunction-associated steatohepatitis. It is the more serious inflammatory form of what is now called metabolic dysfunction-associated steatotic liver disease (MASLD). Many people still recognize the older terms “fatty liver disease,” “NAFLD” and “NASH.” The terminology has changed, but we’re largely talking about the same disease spectrum. With MASH, there is not only excess fat in the liver but also inflammation and liver-cell injury. This can eventually cause fibrosis or scarring.
2. What causes MASH?
There isn’t one single cause. MASH is closely associated with metabolic dysfunction: particularly obesity, insulin resistance or diabetes, abnormal cholesterol and triglycerides, and other features of metabolic syndrome. Genetics and other factors also influence why one person with fatty liver develops significant inflammation and fibrosis while another person does not have it.
3. Who is most at risk?
The highest-risk group includes people with the metabolic syndrome, which includes two or more of the following: Type 2 diabetes, obesity, hypertension and high cholesterol. Not everyone with these conditions develops MASH, and people who don’t fit the stereotypical picture can still develop it. That’s one reason why screening and risk assessment are important.
4. I don’t drink alcohol. How did I get fatty liver disease?
That is a very common misconception. You do not have to drink alcohol to develop fatty liver disease. In MASLD and MASH, the primary drivers are metabolic rather than alcohol-related. The liver accumulates excess fat. In some patients, that progresses to inflammation and fibrosis.
5. What happens if MASH goes untreated?
The major concern is progressive fibrosis. Some patients remain stable for years, but others can progress from early fibrosis to advanced fibrosis and eventually cirrhosis. Once cirrhosis develops, patients are at risk for complications like portal hypertension, liver failure and liver cancer. Cardiovascular disease is also an important cause of illness and death in this population. Progression isn’t inevitable though. Identifying higher-risk patients is precisely why we’re putting so much effort into better noninvasive testing and treatment.
6. How is MASH treated?
Treatment begins with addressing the underlying metabolic disease. Weight loss; healthy nutrition; regular physical activity; and good control of diabetes, cholesterol and blood pressure remain extremely important. The treatment landscape has also changed dramatically. We now have FDA-approved pharmacologic therapies for appropriate patients with MASH and fibrosis. There are additional drugs in late-stage clinical development. That is one reason this is such an exciting area of research right now.
7. What are the warning signs?
Unfortunately, MASH is often silent. Many patients feel completely well even when they have significant fibrosis. Some people may experience fatigue or vague discomfort in the upper-right abdomen, but symptoms are unreliable. Advanced liver disease can eventually produce swelling, jaundice, confusion, gastrointestinal bleeding and other symptoms. Our objective is obviously to identify disease long before someone reaches that stage.
8. How is MASH typically diagnosed?
We increasingly use a stepwise, noninvasive approach. Routine laboratory tests can provide clues and help identify patients who need further evaluation. We then have more sophisticated tools like FibroScan® that measures liver stiffness and fat; blood-based fibrosis tests like ELF™ tests; and imaging techniques such as MRE and MRI-PDFF.
A liver biopsy remains an important diagnostic and research tool because it can directly demonstrate steatosis, inflammation, ballooning injury and the degree of fibrosis. One of the major goals of modern liver research is to obtain more of this information accurately without requiring everyone to undergo a biopsy.
9. Why is the Louisiana Research Center conducting a study on MASH?
This is an area of enormous unmet need. MASH is common, frequently underdiagnosed and potentially progressive. However, many people don’t know they have it until significant liver damage has occurred.
At the Louisiana Research Center (LRC), our goal is to help evaluate new approaches that may allow us to identify these patients earlier and ultimately treat them more effectively. Clinical trials are how we determine whether a promising new therapy is actually safe and effective.
10. In simple terms, what is this study trying to find out?
We’re trying to determine whether this investigational treatment can safely improve MASH; and (importantly) reduce, prevent or reverse progression of liver fibrosis compared with the study’s control treatment.
11. What is being studied, and how could it potentially help people with MASH?
We’re studying various investigational therapies designed to address MASH. Researchers want to determine whether it can improve MASH by using noninvasive tests that measure fibrosis and metabolic parameters, as well as whether it can do so safely. That is what the clinical trial is designed to establish. We don’t assume beforehand that the treatment will work.
12. How long has this research been underway, and what stage is it in?
That is protocol-specific. We have several active MASH drugs and programs.
13. Who is eligible?
Eligibility is very specific, and it varies by study. It may involve age, metabolic risk factors, evidence of MASH and the degree of liver fibrosis, along with laboratory and other medical criteria. Someone doesn’t need to figure out whether they qualify on their own. Our research team can perform an initial screening and explain whether the study might be appropriate for them.
14. What does participation actually look like?
Clinical trials involve more monitoring than routine medical care. Participants may have office visits, blood testing, imaging and specialized liver assessments. Depending upon the protocol, there may also be procedures like a liver biopsy. Many studies use noninvasive tests instead. Before anyone enrolls, our research team goes through the entire schedule so that the patient knows exactly what participation involves.
15. Are there costs, and is compensation provided?
Any study-related procedures or testing are paid for by the sponsor according to the clinical-trial protocol rather than billed as routine care. Studies also typically provide compensation for time and travel. The exact arrangements vary by study, and our coordinators explain those details before a patient decides whether to participate.
16. What are the potential benefits?
A participant may receive additional monitoring and contribute to research that could improve future treatment of MASH.
Our Louisiana Research Center tagline is “Research Today. Medicines Tomorrow.” Depending upon the study, there may be a possibility of benefit from the investigational treatment. However, benefits cannot be guaranteed. That’s an important part of informed consent.
17. What are the risks?
Every investigational treatment has potential risks, including side effects that may already be known and potentially others that aren’t yet known. Some study procedures can also carry risks. Before anyone participates, those risks are reviewed carefully during informed consent. Participants have an opportunity to ask questions.
18. What should someone do if they think they might qualify?
Contact the Louisiana Research Center. You don’t have to know whether you have MASH or whether you meet every study criterion. Our research team can ask some preliminary questions, review the appropriate information and determine whether further screening makes sense.
19. What should someone know before deciding to enroll?
Participation is completely voluntary. We want patients to understand what we’re studying, what will be asked of them, the potential risks and potential benefits, and the alternatives to participating. They should ask as many questions as they need to make a decision that is right for them.
20. What support can participants expect?
They’re not doing this alone. Participants have a dedicated research team that follows them throughout the study, coordinates their visits and testing, answers questions, and monitors their safety. If something changes medically or if they have concerns, we want to hear from them.
21. Tell more about the research team.
The Louisiana Research Center (LRC) has been conducting clinical research in Shreveport for more than three decades. Our research program works closely with gastroenterologists and other healthcare professionals experienced in liver and metabolic disease. We have two physicians serving as principal investigators, experienced research coordinators, and dedicated staff responsible for patient safety, protocol compliance and study procedures. Our patients remain at the center of that process.
If you are interested in participating in a clinical trial for MASH or any of our other studies, please fill out this form. We will be in contact to determine if there is a trial that is right for you.
The team at GastroIntestinal Specialists, A.M.C., treats multiple conditions and diseases of the gastrointestinal (GI) tract. Our board-certified physicians have more than 325 years of combined experience in providing quality care you can trust. To schedule an appointment, call (318) 631-9121 or visit gis.md.