Metabolic dysfunction-associated steatohepatitis (MASH) is a serious liver condition that requires early intervention to prevent complications like liver failure and cancer. Treatment strategies range from lifestyle changes that can slow or even reverse liver damage to new medications being tested in clinical trials. Understanding the available options helps patients and their families work with doctors to create a plan that fits their specific needs.

How Treatment Helps Control Liver Damage and Improve Quality of Life

When someone develops MASH, the primary goal of treatment is to reduce the inflammation and scarring in the liver before it progresses to irreversible damage. MASH happens when excess fat builds up in the liver, triggering inflammation and cell damage that can gradually worsen over time^[1]. Treatment focuses on several key objectives: slowing down or stopping the progression of liver scarring (called fibrosis), improving how the liver functions, and reducing the risk of serious complications like cirrhosis (severe scarring that permanently affects liver function) and liver cancer^[9].

The approach to treating MASH depends heavily on how far the disease has progressed and what other health conditions the patient has. Someone with early-stage MASH and mild fibrosis might respond well to lifestyle changes alone, while someone with more advanced scarring may need medications in addition to diet and exercise^[8]. Doctors also consider conditions that often occur alongside MASH, such as type 2 diabetes, obesity, high cholesterol, and high blood pressure, because managing these problems helps protect the liver^[1].

Treatment options fall into two main categories: standard approaches that have been used for years, and new therapies being studied in clinical trials. Standard treatment relies mainly on lifestyle modifications, including weight loss, dietary changes, and increased physical activity^[11]. For patients who don’t respond adequately to these measures or who have more severe disease, participating in clinical trials may offer access to promising new medications that target the underlying causes of inflammation and scarring in the liver^[8].

It’s important to understand that MASH is often called a “silent disease” because it may not cause noticeable symptoms until significant liver damage has occurred^[19]. This makes early detection and intervention crucial. When treatment begins early, before extensive scarring develops, there is a much better chance of slowing disease progression and potentially reversing some of the liver damage^[2].

Standard Treatment Approaches for MASH

Lifestyle modification remains the cornerstone of MASH treatment and is recommended for all patients regardless of disease stage. The most effective intervention is weight loss, which has been shown in multiple studies to reduce liver fat, decrease inflammation, and improve liver scarring^[14]. Research indicates that losing 7% to 10% of total body weight can lead to meaningful improvements in liver health, with some patients experiencing reduction in fibrosis and even resolution of MASH^[14].

Weight loss doesn’t have to be dramatic to make a difference. Even modest reductions in body weight can decrease the amount of fat stored in the liver. For people with obesity or those who are overweight, healthcare providers typically recommend gradual, sustainable weight loss through a combination of reduced calorie intake and increased physical activity^[8]. The goal is to create lasting habits rather than quick fixes that are difficult to maintain over time.

Dietary changes play a central role in managing MASH. Healthcare professionals often recommend adopting a Mediterranean diet, which emphasizes fruits, vegetables, whole grains, legumes, nuts, fish, and olive oil while limiting red meat, processed foods, and added sugars^[17]. This eating pattern has been shown to improve liver health even in people who don’t lose significant weight. The Mediterranean diet helps reduce liver fat and inflammation because it is rich in antioxidants and healthy fats while being lower in saturated fats and refined carbohydrates^[17].

Reducing intake of fructose and added sugars is particularly important for people with MASH. Fructose, found in table sugar, high-fructose corn syrup, and many sweetened beverages and processed foods, is metabolized primarily in the liver and can contribute to fat accumulation^[14]. Cutting back on sugary drinks, desserts, and processed snacks can help reduce the burden on the liver.

Physical activity is another essential component of standard MASH treatment. Regular exercise helps in multiple ways: it promotes weight loss, reduces liver fat, improves insulin sensitivity, and decreases inflammation^[17]. The strongest evidence supports regular structured moderate-to-vigorous aerobic exercise for 150 to 240 minutes per week. Aerobic activities include brisk walking, jogging, cycling, swimming, or dancing—anything that gets your heart rate up and makes you breathe harder.

In addition to aerobic exercise, resistance training (also called strength training) should be considered, especially for people who are losing weight through diet or medications. Resistance exercises using weights, resistance bands, or body weight help preserve muscle and bone mass that can be lost during weight reduction^[17]. This is particularly important for older adults and people with sarcopenia, which is the loss of muscle mass and strength that can occur with aging or chronic disease.

Beyond diet and exercise, managing other health conditions that often accompany MASH is crucial. Controlling blood sugar levels in people with diabetes or prediabetes, treating high cholesterol with medications called statins if needed, and managing high blood pressure all contribute to better liver health and reduce the risk of heart disease, which is actually the leading cause of death in people with MASH^[9].

Reducing sedentary behavior—the time spent sitting or lying down while awake—is also important. Even if you exercise regularly, spending many hours each day sitting can negatively affect metabolic health. Simple changes like standing up and moving around every hour, taking short walking breaks, or using a standing desk can help^[17].

Sleep quality and duration matter too. Although the evidence is still emerging, poor sleep and conditions like obstructive sleep apnea have been linked to worse outcomes in people with fatty liver disease^[17]. If you snore loudly, wake up gasping for air, or feel extremely tired during the day despite sleeping enough hours, talk to your doctor about being evaluated for sleep disorders.

Alcohol consumption should be minimized or eliminated entirely. Even though MASH is not caused by alcohol, drinking can add to liver damage and accelerate the progression to cirrhosis^[11]. Healthcare providers typically recommend avoiding alcohol or limiting intake to very small amounts.

For people with medically complicated obesity who haven’t achieved sufficient weight loss through lifestyle changes alone, bariatric surgery (weight-loss surgery) may be considered. Procedures like gastric bypass or sleeve gastrectomy can lead to substantial weight loss and have been shown to improve liver inflammation and fibrosis in people with MASH^[8]. However, surgery carries risks and is typically reserved for those who meet specific criteria and have not succeeded with other approaches.

The duration of lifestyle-based treatment is essentially lifelong. MASH is a chronic condition, and maintaining healthy habits over the long term is necessary to keep the disease under control and prevent it from worsening. Regular follow-up with healthcare providers is important to monitor progress, adjust the treatment plan as needed, and screen for complications like liver cancer in people with advanced fibrosis or cirrhosis^[9].

While lifestyle changes form the foundation of MASH treatment, one medication has recently received approval from the U.S. Food and Drug Administration specifically for MASH. Resmetirom is a drug that was approved in 2024 for treating MASH with liver fibrosis. It works as a thyroid hormone receptor beta (THR-β) agonist, meaning it activates specific receptors in the liver that help regulate fat metabolism^[12][13]. In clinical trials, resmetirom demonstrated the ability to reduce liver scarring and improve other measures of liver health^[12].

The clinical trial of resmetirom is still ongoing, so researchers continue to collect data about its long-term effectiveness and safety^[12]. Like all medications, resmetirom can cause side effects. Healthcare providers prescribe it based on the severity of a patient’s liver disease and their individual circumstances.

Promising New Treatments Being Tested in Clinical Trials

Research into MASH treatments has accelerated dramatically in recent years, with dozens of new drugs being studied in clinical trials around the world. These investigational therapies target different mechanisms that contribute to liver inflammation, fat accumulation, and scarring^[10]. While none of these experimental treatments should be considered proven or standard therapy yet, understanding what’s being studied can help patients make informed decisions about participating in research.

Clinical trials are conducted in phases. Phase I trials focus primarily on safety, determining whether a new drug is safe for humans and identifying the appropriate dose range. Phase II trials assess whether the drug is effective and continue to evaluate safety. Phase III trials compare the new treatment to current standard treatments (or placebo) in larger groups of patients to confirm effectiveness and monitor side effects^[10].

One of the most promising categories of drugs being studied for MASH includes medications that were originally developed for diabetes but have shown powerful effects on weight loss and liver health. These are called incretin-based therapies, and they work by mimicking hormones that regulate blood sugar and appetite^[10].

GLP-1 receptor agonists are a type of incretin-based therapy that activate receptors for a hormone called glucagon-like peptide-1. These drugs help lower blood sugar, reduce appetite, and promote weight loss. In people with MASH, GLP-1 agonists have been shown to reduce liver fat and inflammation. Some examples of GLP-1 drugs being studied or already used in related conditions include semaglutide and liraglutide^[10].

Even more exciting are dual agonists and triple agonists—medications that activate multiple hormone receptors at once. For example, some dual agonists activate both GLP-1 receptors and receptors for another hormone called GIP (glucose-dependent insulinotropic polypeptide). Triple agonists add activation of glucagon receptors to the mix^[10]. These combination approaches appear to have stronger effects on weight loss and metabolic health than single-hormone drugs, and early trial results show promising improvements in liver inflammation and fibrosis^[13].

Another major category of experimental MASH treatments includes drugs that modify how the liver metabolizes fats and manages inflammation. PPAR agonists are one such group. PPAR stands for peroxisome proliferator-activated receptors, which are proteins inside cells that regulate fat and sugar metabolism. Different subtypes of PPARs (alpha, delta, and gamma) control different aspects of metabolism^[10].

Some PPAR agonists activate just one receptor subtype, while others are dual or pan-PPAR agonists that activate multiple subtypes simultaneously. Clinical trials have tested various PPAR agonists in people with MASH, with results showing improvements in liver inflammation and sometimes in fibrosis as well^[13]. These drugs work by improving how the liver and other tissues handle fats and by reducing inflammation.

FGF21 analogs represent another promising approach. FGF21 stands for fibroblast growth factor 21, a hormone naturally produced by the liver that plays an important role in regulating metabolism. FGF21 analogs are laboratory-made versions of this hormone that have been modified to last longer in the body^[10]. These drugs help reduce liver fat, improve insulin sensitivity, and may reduce liver scarring. Clinical trials of FGF21 analogs have shown encouraging results in reducing liver fat content and improving metabolic markers^[13].

Thyroid hormone receptor beta agonists like resmetirom (mentioned earlier as the recently approved drug) continue to be studied in ongoing trials to better understand their long-term benefits and optimal use. These drugs work by activating specific thyroid hormone receptors in the liver, which increases the breakdown of fats and cholesterol^[10].

Fatty acid synthase inhibitors represent a novel approach to treating MASH. These drugs block an enzyme called fatty acid synthase, which is involved in producing new fat molecules in the liver. By inhibiting this enzyme, these medications may reduce fat accumulation and the resulting inflammation and scarring^[10]. Clinical trials of fatty acid synthase inhibitors are in earlier phases, but initial results have been promising.

Several clinical trials have reported preliminary results showing that these experimental treatments can improve important clinical parameters. For example, some trials have shown reductions in liver enzyme levels (markers of liver damage), decreases in liver fat measured by imaging tests, improvements in liver inflammation seen on biopsy, and even reduction in liver fibrosis^[13]. Safety profiles have varied depending on the specific drug, with some causing side effects like gastrointestinal symptoms, changes in lipid levels, or other metabolic effects.

Researchers are also exploring combination therapies—using two or more drugs together that target different aspects of MASH disease processes. The rationale is that MASH results from multiple interconnected problems (fat accumulation, inflammation, insulin resistance, scarring), so attacking several of these at once might be more effective than targeting just one^[10]. Early-stage trials of combination treatments are underway, though it’s too soon to know which combinations will prove most beneficial.

An important aspect of current MASH research involves developing better ways to measure treatment success without always requiring liver biopsies, which are invasive. Scientists are working on identifying biomarkers—measurable substances in blood or other body fluids that indicate disease severity or improvement. Improved biomarkers and non-invasive tests would make it easier to monitor patients and assess whether treatments are working^[10].

There is also growing interest in personalized medicine approaches for MASH. Researchers recognize that not all patients with MASH are the same—they have different underlying causes, different genetic factors, different comorbidities, and different rates of disease progression. Future treatment strategies may involve tailoring therapy based on a patient’s specific disease characteristics, genetic profile, and metabolic problems^[10].

Most common treatment methods

• Lifestyle modifications
  • Weight loss of 7-10% of body weight through calorie reduction and increased physical activity, which can reduce liver fat and improve inflammation^[14]
  • Mediterranean diet emphasizing fruits, vegetables, whole grains, fish, and olive oil while limiting processed foods and added sugars^[17]
  • Regular aerobic exercise for 150-240 minutes per week, such as brisk walking, cycling, or swimming^[17]
  • Resistance training to preserve muscle and bone mass during weight loss^[17]
  • Reducing sedentary behavior by increasing daily movement and limiting prolonged sitting^[17]
  • Minimizing or eliminating alcohol consumption^[11]
• Medical management of related conditions
  • Blood sugar control in patients with type 2 diabetes or prediabetes^[9]
  • Cholesterol management with statins if needed^[9]
  • Blood pressure control^[9]
• FDA-approved pharmacotherapy
  • Resmetirom, a thyroid hormone receptor beta agonist approved for MASH with fibrosis, which helps regulate liver fat metabolism^[12][13]
• Incretin-based therapies (in clinical trials)
  • GLP-1 receptor agonists that reduce appetite, promote weight loss, and decrease liver fat and inflammation^[10]
  • Dual agonists activating both GLP-1 and GIP receptors with stronger effects on weight and metabolism^[10]
  • Triple agonists activating GLP-1, GIP, and glucagon receptors^[10]
• Metabolic modulators (in clinical trials)
  • PPAR agonists (single, dual, or pan-PPAR) that regulate fat and sugar metabolism and reduce inflammation^[10][13]
  • FGF21 analogs that reduce liver fat, improve insulin sensitivity, and may reduce scarring^[10][13]
  • Thyroid hormone receptor beta agonists being studied for long-term effects^[10]
  • Fatty acid synthase inhibitors that block fat production in the liver^[10]
• Bariatric surgery
  • Weight-loss surgery such as gastric bypass or sleeve gastrectomy for patients with medically complicated obesity who haven’t responded to lifestyle changes, which can improve liver inflammation and fibrosis^[8]