What is the difference between MAFLD (Metabolic Associated Fatty Liver Disease) and MASLD?

Difference Between MASH and MASLD

MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease) is the umbrella term that encompasses the entire spectrum of fatty liver disease associated with metabolic dysfunction, while MASH (Metabolic dysfunction-Associated SteatoHepatitis) specifically refers to the more severe inflammatory subtype of MASLD with hepatocyte ballooning and inflammation on histology. 1

Key Differences and Definitions

MASLD

• Defined as the presence of hepatic steatosis (identified by imaging or biopsy) in conjunction with at least one cardiometabolic risk factor 1
• Replaces the former term NAFLD (Non-Alcoholic Fatty Liver Disease)
• Represents the entire spectrum of metabolic-related fatty liver disease
• Diagnosis requires:
  • Documented hepatic steatosis (via imaging or biopsy)
  • Presence of at least one cardiometabolic risk factor
  • No other discernible cause of liver disease

MASH

• Specifically refers to the inflammatory subtype of MASLD
• Characterized by steatosis PLUS inflammation and hepatocyte ballooning on histology 1
• Replaces the former term NASH (Non-Alcoholic SteatoHepatitis)
• Associated with higher risk of progression to advanced fibrosis, cirrhosis, and liver-related complications
• Diagnosis requires liver biopsy showing:
  • Steatosis
  • Inflammation
  • Hepatocyte ballooning

Diagnostic Classification

The 2023 international consensus defines these conditions within a broader framework of Steatotic Liver Disease (SLD) 1, 2:

1. SLD: Any liver disease with steatosis as a primary feature
2. MASLD: SLD with at least one cardiometabolic risk factor
3. MASH: MASLD with inflammation and ballooning on histology
4. MetALD: Cases with both metabolic dysfunction and moderate alcohol consumption (20-50g/day for women, 30-60g/day for men)
5. ALD: Alcohol-related liver disease (>50g/day for women, >60g/day for men)

Clinical Significance of the Distinction

The distinction between MASLD and MASH is clinically important for several reasons:

• Prognosis: MASH carries a higher risk of progression to advanced fibrosis, cirrhosis, and liver-related mortality compared to MASLD without inflammation 1
• Treatment intensity: MASH typically requires more aggressive management approaches
• Monitoring frequency: MASH patients need closer follow-up
• Clinical trials: Most pharmacological treatments target MASH specifically rather than MASLD as a whole 1

Relationship to Previous Terminology

There is nearly complete overlap between the old NAFLD and new MASLD populations, with 99.8% accordance in tertiary care cohorts and only 5.3% of individuals with NAFLD not fulfilling MASLD criteria in population studies 1. The evidence generated under the NAFLD definition can therefore be fully extrapolated to individuals with MASLD.

Diagnostic Approach

1. Identify steatosis: Through imaging (ultrasound, CT, MRI) or biopsy
2. Assess cardiometabolic risk factors: Obesity, type 2 diabetes, dyslipidemia, hypertension
3. Exclude other causes: Significant alcohol consumption, medications, genetic disorders
4. Determine if MASH is present: Requires liver biopsy showing inflammation and ballooning

Important Caveats

• Liver biopsy remains the gold standard for diagnosing MASH, but is not practical for routine clinical practice due to invasiveness 1
• Non-invasive tests are increasingly used to assess fibrosis progression but may provide limited information about treatment response 1
• The MetALD category (combined metabolic and moderate alcohol consumption) represents a distinct entity to which recommendations generated for "pure" MASLD may not fully apply 1

The new terminology better reflects the pathophysiology of these conditions and removes the stigmatizing "non-alcoholic" label while emphasizing the metabolic nature of the disease.