NAFLD / MASLD (Fatty Liver Disease)

•RCT evidence— Resmetirom approved 2024 for NASH; lifestyle remains foundation

The renaming

In 2023 the field replaced NAFLD with MASLD (metabolic-dysfunction- associated steatotic liver disease) to reflect that the condition is defined by metabolic dysfunction rather than absence of alcohol. NASH (non-alcoholic steatohepatitis) is now MASH (metabolic-dysfunction- associated steatohepatitis).

Spectrum

• Simple steatosis: fat in liver, no significant inflammation.
• MASH: fat + inflammation + hepatocyte injury.
• Fibrosis stages F1–F4.
• Cirrhosis (F4) → decompensation, HCC risk.

Why it matters for longevity

• Independent cardiovascular risk factor (often the dominant CV risk).
• Marker of systemic insulin resistance.
• Leading indication for liver transplantation in many countries.
• HCC risk even in non-cirrhotic NASH.

Screening

• FIB-4 score (age, AST, ALT, platelets): excludes advanced fibrosis if low; intermediate/high → further evaluation.
• FibroScan transient elastography: measures liver stiffness.
• MRI proton density fat fraction (MRI-PDFF): quantifies fat content non-invasively.

Treatment

• Weight loss: 7–10% sustained weight loss reverses steatosis and inflammation in most patients.
• Diet: Mediterranean; reduce fructose, refined carbs, alcohol.
• Exercise: independent of weight loss reduces liver fat.
• Pharmacotherapy:
  • Resmetirom (Rezdiffra): first FDA-approved (March 2024) drug for MASH with significant fibrosis.
  • GLP-1 agonists (semaglutide, tirzepatide): NASH improvement in trials.
  • Vitamin E in non-diabetic MASH (PIVENS trial).

Related entries

Metabolic syndrome, Type 2 diabetes, GLP-1 agonists, Mediterranean diet.