New MASLD Global Consensus Recommendations Streamline Current Guidelines

New global guideline consensus for recommendations on metabolic dysfunction-associated steatotic liver disease (MASLD) streamline and simplify existing recommendations in current guidelines and guidance documents to facilitate their implementation in clinical practice.1

Following a comprehensive review of 61 documents published from 2018-2025, major areas of discordance were identified and subject to a Delphi consensus-building process to establish consensus recommendations for areas of disagreement, including methods and thresholds used to quantify alcohol consumption, types and thresholds of noninvasive tests (NITs) used to identify high-risk MASLD patients, and frequencies and modalities used to screen for MASLD-related hepatocellular carcinoma (HCC).1

“As the growing burden of MASLD became increasingly recognized, a large number of clinical practice guidelines, guidance, and similar documents have been developed to assist clinicians in the management of people with MASLD,” Zobair Younossi, MD, MPH, professor and chairman of the Beatty Liver and Obesity Research Program, Inova Health System, and chairman of the Global NASH Council, and colleagues wrote.1 “Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field.”

To address these differences and increase implementation of these recommendations in clinical practice, especially with the availability of resmetirom (Rezdiffra) as the first and only FDA-approved MASH therapeutic, investigators conducted a comprehensive search for country-specific guidelines, guidance papers, clinical practice guidelines, or expert consensus statements regarding MASLD and MASH published from January 2018-January 2025 using PubMed, Embase, Web of Science, and society websites.1

A steering committee of MASLD experts from different regions of the world, including gastroenterologists, hepatologists, nutrition experts, primary care physicians, and endocrinologists/diabetologists, as well as patient representatives, was developed. Once focus areas for the guideline consensus were established, relevant data were collected from 61 selected documents and assessed across 8 specific domains with 145 variables.1

Variables with <50% concordance were used for the Delphi statement development and distribution via a self-administered online survey. Based on the levels of agreement and qualitative feedback in the Delphi survey, the discordant statements were revised and subsequent rounds of the Delphi process were held until all statements achieved ≥ 67% super majority.1

A total of 4 rounds of Delphi were conducted: 46 statements were generated for Round 1, 32 statements for Round 2, 16 statements for Round 3, and 8 statements for Round 4, whereby 100% of statements achieved > 90% agreement.1

While no items regarding the epidemiology and progression of MASLD required inclusion in the Delphi process, several areas related to the screening for MASLD did.1

After 4 steps, consensus was reached on investigating and stratifying for high risk MASLD in patients with type 2 diabetes, obesity with ≥ 1 additional cardiometabolic risk factors, and persistent ALT/AST elevation for ≥ 6 months, beginning with calculation of the fibrosis-4 (FIB-4) score followed by second-line testing, typically vibration-controlled transient elastography, in patients with a score ≥ 1.3.1

For alcohol consumption, the consensus recommends it be assessed during a clinical interview using the Alcohol Use Disorder Identification Test and the phosphatidylethanol test. Assessments for common comorbidities such as type 2 diabetes, dyslipidemia, cardiovascular disease, and kidney disease were also recommended.1

Identified MASLD treatment strategies included lifestyle interventions, such as recommendations for a healthy diet, increased physical activity, and decreased sedentary time. Additionally, it was recommended that treatment of metabolic comorbidities be optimized in patients with MASLD, regardless of MASH treatment.1

While most of the included guidelines did not provide concise guidance on what a ‘healthy lifestyle’ entails, almost all guidelines mention consideration of a Mediterranean-style diet, which can be used to achieve weight loss goals: ≥5% to reduce liver fat, ≥7%–10% to improve inflammation, and ≥10% to reduce fibrosis. Investigators also emphasized the importance of plant-based foods, lean proteins, and healthy fats while discouraging ultra-processed and sugary foods, as well as 150–300 minutes of moderate or 75–150 minutes of vigorous exercise per week, reducing alcohol intake, and smoking cessation.1

There was strong consensus that bariatric surgery can be beneficial for weight loss in noncirrhotic MASH patients who meet established criteria. However, it was not specifically recommended for the treatment of MASH.1

Additionally, due to a lack of sufficient evidence and balancing risks and benefits, vitamin E supplementation was not recommended as a MASH-targeted therapy, except in select individuals without type 2 diabetes or cirrhosis. Similarly, ursodeoxycholic acid or omega-3 fatty acids were not recommended as a treatment for people with MASH. While GLP-1 RAs show promise in phase 3 trials, they are not yet approved for MASH.1

Although all 14 statements related to treatment with resmetirom achieved ≥ 70% agreement, several comments were deemed important for inclusion in the second through fourth rounds of the Delphi process. Beyond resmetirom, which is already FDA-approved for MASH, 61% of guidelines discussed drugs in development for MASH, most commonly peroxisome proliferator-activated receptor agonists, farnesoid X receptor agonists, and CCR2/CCR5 inhibitors.1,2

HCC screening is recommended for MASH-associated cirrhosis following the same protocols as for other etiologies. While investigators noted noncirrhotic MASH patients generally do not meet the risk threshold for routine HCC surveillance, those with bridging fibrosis, family history, or ongoing alcohol use may warrant individual assessment.1

Of the reviewed guidelines, 13 (21%) mentioned pregnancy but only 2 (1%) made any recommendations. While mention of pediatric populations were more common (65%), about half (55%) provided any recommendations and few provided clear diagnostic criteria or screening thresholds.1

“Through an in-depth review of recent MASLD guidelines or similar documents from around the world, and the Delphi process with global MASH experts, we have developed consensus recommendations for busy clinicians, investigators concluded.1 “Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment.”

References

1. Younossi ZM, Zelber-Sagi S, Lazarus JV, et al. Global Consensus Recommendations for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis. Gastroenterology. doi:https://doi.org/10.1053/j.gastro.2025.02.044

2. Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed April 15, 2025. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash