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MASH Matters GI and Hepatology Practice

CE / CME

MASH Matters: New Evidence and Its Application to Gastroenterology and Hepatology Practice

Physician Assistants/Physician Associates: 0.50 AAPA Category 1 CME credit

Nurse Practitioners/Nurses: 0.50 Nursing contact hour

Physicians: maximum of 0.50 AMA PRA Category 1 Credit™

Released: June 23, 2025

Expiration: June 22, 2026

Mazen Noureddin
Mazen Noureddin, MD, MHSc
CME/CE Information

Activity

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SLD: Inclusive Rather Than Exclusive Criteria

First, let us discuss the new terminology of “steatotic liver disease” (SLD), which was published within the past couple of years. Although a lot of terms have changed, the overall concept is still the same. Fatty liver, the old and common terminology, is now called SLD. This occurs when steatosis (or excess fat) is present in the liver.1

It is divided into multiple buckets. What used to be called “nonalcoholic fatty liver disease” is now called “MASLD.” This terminology was changed because many patients felt stigmatized with the term “nonalcoholic fatty.” Then MASLD can progress to the more advanced form: MASH. In simplistic terms, MASH occurs in addition to excess fat in the liver, leading to inflammation and cell injury. MASH is the cascade that eventually leads to fibrosis and cirrhosis.

What also comes with this change in terminology for MASLD is that these patients have metabolic syndrome with or without a slight increase in alcohol intake (or more than recommended), but they do not meet the criteria for alcohol-associated or alcohol-related liver disease (ALD). These amounts are listed on the slide: weekly intake of 140-350 g for females and 210-420 g for males. There is a new category now, too, called MetALD—“Met” for metabolic plus ALD. This disease category is used for patients with both metabolic syndrome and increased alcohol intake, with the weekly intakes as mentioned prior. Then there are other etiologies of SLD like drug-induced liver injury or viral hepatitis.2 

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Classification of Steatotic Liver Disease

It also is important to know what the metabolic risk factors are. As listed in the guidelines, patients need to meet at least one of 5 criteria: BMI ≥25 kg/m2, a waist circumference >94 cm for males and 80 cm for female, elevated blood glucose or A1C (or history of or treatment for T2D), blood pressure ≥130/85 mm Hg or antihypertensive treatment, plasma triglycerides ≥150 mg/dL, or decreased high-density lipoprotein or lipid lowering treatment.2

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Prevalence of MASLD and MASH

Moving onto the prevalence of MASLD/MASH, we generally know how to deal with the disease and which populations we need to treat around the world, especially Western countries like the United States. As illustrated here, the prevalence of MASLD worldwide is 25%. In the United States, new data are showing that the prevalence of MASLD is approximately 34%. MASH is the advanced form of MASLD and is thought to be prevalent in 3% to 5% of people globally. Finally, the percentage people at risk of developing cirrhosis because of MASLD/MASH is 1% to 2%.3-6

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The Pathogenic Relationship Between Diabetes and MASH

It is important to remember that MASLD is a metabolic phenomenon and is caused by insulin resistance. That is why MASH and T2D are closely tied together. It starts with insulin resistance, which leads to an increased secretion of cytokines and lipolysis free fatty acid. There is lipotoxicity and increased TGF-β and TNF-α. What that leads to is insulin resistance in the liver and muscle, activation of a cascade of proinflammatory pathways and eventually the activation of stellate cells and fibrosis. It is a vicious cycle between insulin resistance and liver/muscle injury, which falls under the same metabolic umbrella.7

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Screening for MASLD/MASH

On this slide is the American Gastroenterology Association’s (AGA’s) recommendation for screening for MASLD/MASH. Healthcare professionals (HCPs) should not screen the entire population; rather, HCPs should only screen those with increased metabolic risk factors. The AGA, American Association for the Study of Liver Disease, American Diabetes Association, and American Association for Clinical Endocrinology agree in recommending the screening of high-risk patients only. Why? Because these patients are increased risk for MASLD and fibrosis. Here, specifically, the AGA recommends screening those with 2 or more metabolic risk factors: T2D (other associations include those with prediabetes), steatosis on imaging, or elevated liver enzymes.

What testing should HCPs do? There is the Fibrosis-4 (FIB-4) index. It creates a value based on patients’ age, liver enzymes, and platelet count. If that value is <1.3, the patient is at low risk and HCPs should check on the patient periodically (every 2-3 years). When conducting an annual retinopathy or nephropathy check on your patients with T2D, consider doing the FIB-4 index, too. If the value is 1.3-2.67, then the patient is at intermediate risk, and if the value is >2.67, then the patient is at high risk. At this point, patients should be referred to gastroenterology/hepatology for further testing including vibration-controlled transient elastography (VCTE), which is an imaging technique, or other blood tests to confirm patients’ diagnosis.8-10

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MASLD/MASH Management by Fibrosis Stage

This slide outlines the breakdown of the risk groups. Patients at low risk have an FIB-4 <1.3 or liver stiffness measurement (LSM) <8 kPa. If the LSM is >8 kPa, then HCPs should start worrying about them, especially if it is ≥12 kPa (higher risk). This is when I start asking myself if they have a fibrosis score of F3 or F4.

All patients are recommended, regardless of their risk category, to integrate lifestyle interventions and weight loss programs into their management. For patients with obesity, this would also include antiobesity agents or bariatric surgery, if appropriate. Once the LSM is ≥8 kPa, the guidelines recommend pharmacologic therapies for MASH. In addition, these patients should be treated to control for cardiovascular risk factors and diabetes management, if applicable, with preference for GLP-1 RAs and pioglitazone as they have the most data to support their use in MASH.8

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ADA 2025 MASLD Treatment Algorithm for Individuals With Prediabetes or Diabetes

The figure on this slide comes from the American Diabetes Association. It looks at MASH as part of metabolic syndrome, where HCPs must manage obesity and/or diabetes via pharmacologic therapy in addition to diet and exercise. As I mentioned previously, we now have MASH pharmacotherapy, which is resmetirom. These treatments are recommended in patients with increased steatosis and LSM: MASLD and F2-F3 fibrosis (at risk for MASH).11,12

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