A multinational panel has unified competing guidance on metabolic dysfunction–associated steatotic liver disease and steatohepatitis, producing algorithms for screening, risk stratification, lifestyle therapy, management of cardiometabolic comorbidities, and the use of resmetirom, the first FDA-approved medication for noncirrhotic metabolic dysfunction–associated steatohepatitis with F2–F3 fibrosis.
"Through an in-depth review of recent MASLD [metabolic dysfunction–associated steatotic liver disease] guidelines or similar documents from around the world, and the Delphi process with global MASH experts, we have developed consensus recommendations for busy clinicians," noted the panel members.
Sixty-one guidance documents published between 2018 and January 2025 were reviewed and areas of disagreement were resolved through a four-round Delphi process, noted study author Zobair M. Younossi, of the Beatty Liver and Obesity Research Program, at Inova Health System, in Falls Church, Virginia.
"Although our results are grounded in sound methodology, it is important to point out that these recommendations are not meant to replace existing, recent guidelines," wrote Dr. Younossi and colleagues. "The goal of this process was to address areas of discordance in recommendations among the guidelines and provide easy-to-use guidance for the care of patients with MASLD."
MASLD affects roughly a third of adults; metabolic dysfunction–associated steatohepatitis (MASH) drives fibrosis, cirrhosis, HCC risk, poor quality of life, and substantial costs. Prior variability across societies’ recommendations has hindered implementation; the new consensus aims to standardize the first steps of evaluation and the introduction and monitoring of resmetirom in routine practice.
Clinicians should identify high-risk MASLD in patients with type 2 diabetes (T2D); those with obesity plus at least one cardiometabolic risk factor; or anyone with persistent aminotransferase elevations 6 months of more after alternative causes are excluded. Alcohol use should be assessed to distinguish MASLD from Met-ALD and ALD, and diagnosis should be assigned using standardized alcohol thresholds. Comorbidity screening for CVD, diabetes, dyslipidemia, and CKD is recommended.
Patients with FIB-4 under 1.3 (under 2 if 65 years or older) are low risk and can remain in primary care with retesting every 1 to 3 years. Those at or above the cutoff should undergo vibration-controlled transient elastography (VCTE) or another validated second-line NIT; liver stiffness of 8 kPa or more indicates risk for advanced fibrosis and merits specialty evaluation.
The panel recommended a Mediterranean-style, plant-forward diet; reduced ultraprocessed and sugar-sweetened foods; and prescribed 150 to 300 minutes/week of moderate or 75 to 150 minutes/week of vigorous activity. Weight-loss benchmarks are 5% or more (3% to 5% if normal/lean BMI) for steatosis, 7% to 10% for inflammation, and 10% or greater for fibrosis improvement.
Dr. Younossi and colleagues also recommended prioritizing GLP-1 receptor agonists for patients with T2D, obesity, or both until MASH labeling is granted. SGLT2 inhibitors and other medications treat diabetes but are not MASH-targeted therapies. Routine vitamin E for MASH is not recommended given limited benefit and potential risks, but some legacy guidance allows selective use in patients without diabetes or cirrhosis.
The consensus recommendations outline a clear, noninvasive test (NIT)-based pathway for initiating and monitoring resmetirom therapy. Patients considered eligible are those with noncirrhotic MASH and evidence of F2–F3 fibrosis by NITs.
Treatment should be initiated when vibration-controlled transient elastography (VCTE) indicates a liver stiffness measurement (LSM) in the high range consistent, but not exceeding the threshold typically associated with cirrhosis. For patients with borderline LSM values just below this range, a second concordant noninvasive test (NIT) confirming advanced fibrosis is required before proceeding. When LSM approaches the upper end of the moderate range, cirrhosis must be carefully excluded through both a second NIT and supporting clinical or laboratory data, such as platelet counts. Resmetirom should not be prescribed if LSM is above the cirrhotic threshold or if cirrhosis is otherwise diagnosed.
Once treatment is initiated, monitoring is structured and systematic. Safety assessments should be performed at 3, 6, and 12 months. A 6-month VCTE may be used to gauge early trends, although these results should not drive treatment decisions on their own. The critical assessment point is at 12 months, when efficacy or futility should be judged using NITs. A reduction in LSM of 30% or more is considered a clinically meaningful improvement. Importantly, a lack of ALT improvement at this stage should not, by itself, lead to treatment discontinuation. Instead, futility should only be declared if two separate NITs demonstrate concordant worsening.
Conflict of interest statements are available in the published article below.
Source: Gasroenterology
