UCLA Health liver specialists have helped develop an algorithm for treating patients with metabolic dysfunction-associated steatohepatitis (MASH) and moderate to advanced fibrosis.
MASH is a serious liver disease that causes inflammation and liver damage. Over time, MASH can lead to fibrosis, or scarring. Severe fibrosis can progress to cirrhosis and liver failure. MASH has become a leading cause of cirrhosis and a common reason for a liver transplant. It can also raise the risk of liver cancer.
Recently, the Food and Drug Administration approved the first two medicines to treat MASH in adults with moderate to advanced fibrosis. But the drugs work differently and have different effects, according to a review led by UCLA Health.
Published in Digestive Diseases and Sciences, the review includes an algorithm to help doctors choose between the treatments. Resmetirom is a daily pill, while semaglutide comes as a daily pill or a weekly shot.
“We’re excited to have not one but two drugs that are available to our patients,” says senior author Sammy Saab, MD, medical director of the UCLA Health Adult Liver Transplant Program and chief of hepatology.
“Both are effective. But there may be nuances that favor one over the other in a particular patient,” Dr. Saab explains. The patient’s other health issues, risk factors and preferences can help guide treatment.
At UCLA Health, liver specialists work with cardiologists and nutrition experts as part of a multidisciplinary approach to liver care.
“We need to make sure we look at the big picture — not just one part of the patient, but their whole journey,” Dr. Saab says.
A new era in MASH management
MASH is a more severe type of metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD, which used to be called nonalcoholic fatty liver disease, occurs when extra fat builds up in the liver.
Conditions such as obesity (body mass index higher than 30), type 2 diabetes, insulin resistance and high cholesterol should raise suspicion for MASLD or MASH.
MASLD is becoming more common. It affects one in three people worldwide and about 100 million adults in the U.S. Often, they don’t have symptoms.
In about 20% of patients, MASLD progresses to MASH. People with MASH also have a higher risk of heart disease, heart attack and stroke.
“The hepatology community has been managing MASLD and MASH for many years without any FDA-approved medications,” says lead author Jason Pan, MD, a transplant hepatologist and gastroenterologist at UCLA Health’s Pfleger Liver Institute.
But until recently, treatment options were limited.
“Previously, we focused on encouraging patients to lose weight. For some patients, we’d refer them for bariatric surgery,” Dr. Pan explains.
Vitamin E and pioglitazone, a diabetes medicine, were sometimes used. But those therapies were not thought to be effective, he adds.
Now that resmetirom and semaglutide are available, MASH management is changing. These drugs can slow or even reverse liver damage before it leads to cirrhosis.
“So how do we select between these new medications, especially when the data on their use is a bit limited?” Dr. Pan continues. Both drugs have been studied in phase 3 clinical trials, but not yet compared directly.
“We thought writing this review would be helpful for fellow providers,” Dr. Pan notes.
Two effective options
Coauthor Brian Horwich, MD, is a general and transplant hepatologist at UCLA Health. MASH has become one of the most common reasons patients are referred to a liver specialist, he says.
“In general, patients are told they have MASH long before they walk in the door to my clinic,” Dr. Horwich notes. “Often, people have carried this diagnosis for many years. They’re now seeking care due to a change or increased awareness of the complications of liver disease.”
The FDA approved resmetirom in 2024. It works on thyroid hormone receptors found in the liver. The drug helps remove liver fat and prevent further liver damage. It doesn’t lead to weight loss, but it can help lower cholesterol.
“I often describe it as like having a good ‘goalie’ against fatty liver disease,” explains Dr. Horwich.
Semaglutide is a GLP-1 medicine. The FDA approved it to treat MASH in 2025. Unlike resmetirom, semaglutide works throughout the body. It triggers weight loss and helps prevent fat from building up in the liver. Semaglutide can also lower blood sugar and help manage pre-diabetes and diabetes.
“In other words, it’s like having a good ‘defense’ for the liver against fat deposits,” Dr. Horwich adds.
Both drugs have side effects that may include nausea, vomiting and diarrhea. But there’s good news for patients.
“The side effects are predictable and manageable. They’re temporary and many improve without intervention,” says Dr. Saab.
Certain patients might benefit from taking both drugs, adds Dr. Pan.
“For example, if your MASH is not responding to your current dose of semaglutide, but you’re not able to tolerate a higher dose, then it would be a natural move to put you on resmetirom,” he says.
The authors agree that deciding which treatment to offer can be challenging.
“Two great options means that it may not always be clear which one is the best for your patient. Sometimes it’s important to just choose one and start treatment, and adjust course if needed,” Dr. Horwich says.
Personalized treatment
Before choosing a medication, fibrosis staging can determine how much scarring has developed. Resmetirom and semaglutide are used for MASH with stage 2 or 3 fibrosis, which is moderate to advanced.
Noninvasive imaging such as FibroScan and MRI with elastography can assess liver fat and fibrosis. Some people with MASH have normal blood test results, so normal aspartate aminotransferase and alanine aminotransferase levels don’t rule out disease.
“We recommend that you identify and stage patients’ obesity, level of insulin resistance and any gastrointestinal symptoms,” says Dr. Pan. Symptoms such as heartburn, abdominal discomfort, or constipation could be made worse by semaglutide.
The risk of heart disease is important. “If their cholesterol panel is highly abnormal, that might sway you toward one form of therapy or another,” notes Dr. Pan.
Cost is a factor, too. Resmetirom and semaglutide should be covered by most insurance plans. But out-of-pocket costs can range from hundreds to thousands of dollars monthly.
According to the algorithm, semaglutide might be a good fit for patients with type 2 diabetes, heart disease or obesity. If weight loss isn’t desired or a patient can’t take a GLP-1, resmetirom may be better.
But medication is only one part of MASH care, the authors stressed. Lifestyle changes are still the foundation. This includes counseling patients to exercise, reduce saturated fats, limit alcohol and follow a Mediterranean-style diet.
Patients can be referred to a registered dietitian for more support if obesity is a major factor.
“Remember, MASH doesn’t occur in a vacuum,” Dr. Saab says. “Don’t forget the underlying issues that put the patient at risk.”
Once treatment starts, labs and symptoms should be monitored. A follow-up visit within one to two months is recommended. It can take at least four to six months to see if fibrosis is improving.
Ultimately, resmetirom and semaglutide offer new hope for addressing the growing burden of MASLD and MASH.
“Advanced liver disease can be very serious. But with these medications, we have the opportunity to prevent liver-related symptoms long before they start,” Dr. Horwich says.
