MASLD Consensus 2025

The **MASLD Consensus 2025** represents a unified and standardized approach to the management of **Metabolic dysfunction-associated steatotic liver disease (MASLD)** and **Metabolic dysfunction-associated steatohepatitis (MASH)**. This consensus was developed using expert opinions and the Delphi methodology to address discordances across existing guidelines and provide globally applicable recommendations. Below is a detailed breakdown of the key aspects of the MASLD Consensus 2025:

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### **Core Objective**

• To simplify and unify global guidelines for the screening, diagnosis, and management of MASLD and MASH.
• The consensus aims to harmonize care worldwide, ensuring early detection, consistent management, and improved research comparability.

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### **Study Scope**

• 61 national and international guidelines from 2018 to 2025 were reviewed to identify inconsistencies and resolve discordances.
• After four Delphi rounds, 46 final consensus statements achieved 100% agreement among experts.

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### **Epidemiology**

• MASLD affects approximately **38% of adults globally**.
• MASH, the progressive form of MASLD, has a prevalence of **5%–7%**.

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### **Major Risk Factors**

• **Type 2 diabetes (T2D)**, **obesity**, and **persistent elevated aminotransferases** are the key indicators for evaluating MASLD.
• These risk factors are central to identifying individuals at higher risk of liver disease progression.

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### **Screening Recommendations**

• **Who to screen:** Individuals with:
• Type 2 diabetes.
• Obesity.
• Chronic liver enzyme elevation lasting ≥6 months.
• **Alcohol thresholds:** To differentiate MASLD from alcohol-associated liver disease:
• Women: ≤20g/day alcohol intake.
• Men: ≤30g/day alcohol intake.
• **Met-ALD classification:** Recognized as a subset of MASLD for individuals with moderate alcohol intake and metabolic risk factors.

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### **Diagnostic Tools**

1. **Primary Diagnostic Tool:**

• **Fibrosis-4 (FIB-4) test** is the first-line, noninvasive assessment for liver fibrosis.
• **<1.3:** Indicates low risk of fibrosis.
• **≥1.3:** Requires further assessment.
• Regional adjustment: In India, a lower FIB-4 threshold of **1.0** is adopted due to population-specific variability.

2. **Secondary Assessment:**

• **Vibration-controlled transient elastography (VCTE)** is recommended as the second-line test for evaluating liver stiffness and fibrosis grading.

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### **Management Strategies**

1. **Lifestyle Modifications:**

• **Weight loss:** Aim for a **5%–10% reduction** in body weight.
• **Diet:** Emphasis on a **Mediterranean-style diet**.
• **Physical activity:** Engage in **150–300 minutes of exercise per week** and reduce sedentary time.

2. **Comorbidity Management:**

• Optimize control of:
• Type 2 diabetes.
• Dyslipidemia.
• Cardiovascular risk factors (based on global cardiometabolic guidelines).

3. **Pharmacologic Guidance:**

• **GLP-1 receptor agonists** and **SGLT-2 inhibitors** are preferred for managing T2D and obesity in MASLD patients. However, these are not yet approved as direct MASH therapies.
• **Vitamin E:** Not recommended for routine MASH therapy due to limited efficacy and safety concerns.

4. **New Therapy Inclusion:**

• **Resmetirom (THR-β agonist):** Recognized as the first FDA-approved drug for MASH with stage F2–F3 fibrosis.
• **Monitoring:** Safety checks at 3, 6, and 12 months.
• **Efficacy:** Assessed at 1 year using non-invasive tests (NITs)—a reduction in ALT alone is not considered a success criterion.

5. **Bariatric Surgery:**

• Recommended for non-cirrhotic MASH patients who meet surgical criteria.
• Not considered a primary treatment for MASH but can significantly improve liver outcomes.

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### **Hepatocellular Carcinoma (HCC) Screening**

• **For MASLD-related cirrhosis:** Screening every 6 months is recommended.
• **For non-cirrhotic high-risk patients:** An individualized screening approach is advised.

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### **Global Implications**

• The MASLD Consensus 2025 introduces a **standardized algorithm** for the management of MASLD and MASH.
• This harmonization is expected to:
• Facilitate early detection of MASLD and MASH.
• Ensure consistent management practices worldwide.
• Improve comparability in clinical research, fostering advancements in treatment and care.

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### **Conclusion**

The MASLD Consensus 2025 provides a comprehensive, evidence-based framework for the global management of MASLD and MASH. By addressing discrepancies in screening, diagnosis, and treatment guidelines, the consensus aims to improve patient outcomes and advance the field of metabolic liver diseases.