Fatty Liver

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) & Metabolic-Associated Steatohepatitis (MASH)

• MASLD (formerly NAFLD) is one of the most common liver conditions, increasing due to obesity and metabolic syndrome.
• MASH (formerly NASH) represents the progressive form, which can lead to cirrhosis.

Types of Fatty Liver Disease

1. Alcohol-Associated Liver Disease (ALD) – Linked to heavy alcohol intake.
2. Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) – Occurs without alcohol consumption, associated with metabolic syndrome (high cholesterol, high blood pressure, obesity).
3. Metabolic-Associated Steatohepatitis (MASH) – The inflammatory and fibrotic progression of MASLD.

Key Facts

• Reversible with lifestyle changes.
• Non-invasive assessment using FibroScan or MRI.
• Fat accumulation >5-10% of liver weight is considered abnormal.
• Risk factors: Obesity, diabetes, high triglycerides, certain medications, and metabolic dysfunction.

Diagnosis

• Often incidental during routine ultrasound screening.
• If liver function tests (LFTs) are normal, MASLD is usually benign.
• If LFTs are abnormal, further specialist assessment is needed.
• Diagnosis is made by excluding other liver diseases (e.g., viral hepatitis).

Treatment

• Address underlying risk factors:
• Weight management
• Better diabetes control
• Reducing alcohol intake (if excessive)

Role of GLP-1 Receptor Agonists

• GLP-1 receptor agonists (GLP-1 RAs), originally developed for type 2 diabetes, show promise in MASLD and MASH management.
• They help by:
• Reducing hepatic lipogenesis (fat accumulation in the liver).
• Improving insulin sensitivity, lowering metabolic dysfunction.
• Modulating inflammation, potentially slowing fibrosis progression.

Key Findings

• Semaglutide (Wegovy, Ozempic): Investigated in Phase III trials for MASH, showing potential for weight loss and liver health improvement.
• Tirzepatide (Zepbound): A GLP-1/GIP dual agonist, demonstrating strong antifibrotic effects in early trials.
• Cardiovascular Benefits: GLP-1 RAs also reduce portal hypertension and heart failure risks in MASLD patients.

Clinical Implications

• Weight loss effects are particularly relevant for MASLD, given its strong link to obesity.
• Anti-inflammatory and antifibrotic properties may help slow disease progression.
• Further research needed to determine long-term efficacy in advanced fibrosis (F2-F3 MASH).