What are the primary management strategies for Non-Alcoholic Steatohepatitis (NASH) versus Metabolic Associated Fatty Liver Disease (MAFLD)?

NASH vs MAFLD: Understanding the Nomenclature and Management Implications

NASH and MAFLD represent overlapping but distinct conceptual frameworks for metabolic fatty liver disease, with MAFLD being a newer, more inclusive diagnostic term that emphasizes metabolic dysfunction rather than excluding alcohol use, but the core management strategies remain identical regardless of which terminology you use. 1, 2

Key Nomenclature Differences

NASH (Nonalcoholic Steatohepatitis):

• Represents the inflammatory subtype within the NAFLD spectrum, characterized by steatosis plus hepatocyte ballooning and inflammation on histology 1
• Requires exclusion of significant alcohol consumption (≤1 drink/day for women, ≤2 drinks/day for men) 1
• Diagnosis traditionally requires liver biopsy showing specific histologic features 1

MAFLD (Metabolic-Associated Fatty Liver Disease):

• A newer diagnostic framework (proposed 2020) that defines fatty liver disease based on the presence of metabolic dysfunction rather than alcohol exclusion 3, 4
• Diagnosed when hepatic steatosis is present along with one of: overweight/obesity (BMI >25 kg/m²), type 2 diabetes, or evidence of metabolic dysregulation 3
• Does not require complete alcohol exclusion, acknowledging that metabolic and alcoholic factors often coexist 4
• Approximately 40% of patients with fatty liver disease are non-obese, and nearly 20% are lean, making the metabolic focus more inclusive 3

Why This Distinction Matters Clinically

The shift from NAFLD/NASH to MAFLD terminology reflects a more accurate pathophysiological understanding—these conditions are fundamentally metabolic diseases that can overlap with modest alcohol use 3, 4. However, from a practical management standpoint, the treatment algorithms are virtually identical because both frameworks target the same underlying metabolic dysfunction 1, 2.

Universal Management Strategy (Applies to Both NASH and MAFLD)

Risk Stratification by Fibrosis Stage

The severity of fibrosis, not the nomenclature used, determines treatment intensity and prognosis: 1, 2

• F0-F1 (No/Minimal Fibrosis): Lifestyle modifications only; excellent prognosis from liver standpoint 2, 5
• F2-F3 (Significant Fibrosis): Lifestyle modifications + pharmacologic therapy consideration + hepatology referral 1, 2
• F4 (Cirrhosis): All of the above + HCC surveillance every 6 months + variceal screening 1, 2

Core Lifestyle Interventions (Foundation for All Patients)

Weight Loss Targets: 1, 2

• Achieve 7-10% total body weight reduction to improve steatohepatitis and potentially reverse fibrosis 2
• Weight loss of 5-7% reduces hepatic fat and inflammation 1, 2
• Weight loss ≥10% achieves fibrosis improvement in 45% of patients 1, 2
• Critical caveat: Weight loss must be gradual (<1 kg/week) as rapid weight loss can precipitate acute hepatic failure, especially in patients with advanced disease 1, 5

Dietary Approach: 1, 2, 5

• Mediterranean diet pattern is the evidence-based recommendation 1, 2, 5
• Caloric deficit of 500-1000 kcal/day (typically 1,200-1,500 kcal/day for women, 1,500-1,800 kcal/day for men) 1
• Emphasize vegetables, fruits, whole grains, legumes, olive oil, fish, and minimal red meat 5
• Low-carbohydrate diets are more effective than low-fat diets for reducing liver fat 1

Exercise Prescription: 2, 5

• 150-300 minutes/week of moderate-intensity exercise OR 75-150 minutes/week of vigorous-intensity exercise 2
• Vigorous-intensity exercise (≥6 METs) is superior to moderate-intensity for improving NASH severity and fibrosis 5
• Exercise reduces hepatic fat independent of weight loss 2

Pharmacologic Treatment (For F2+ Fibrosis or Biopsy-Proven NASH)

GLP-1 Receptor Agonists (Preferred for Patients with Type 2 Diabetes): 2

• Liraglutide demonstrated NASH resolution in 39% vs 9% placebo at 48 weeks in biopsy-proven NASH 2
• Treats both diabetes and liver disease simultaneously 2

Vitamin E: 1, 5

• 800 IU daily for patients with biopsy-confirmed NASH without diabetes or cirrhosis 5
• Improves liver histology in select patients 1

Pioglitazone: 1, 5

• 30 mg daily for patients with biopsy-confirmed NASH without cirrhosis, with or without diabetes 5
• Treats both diabetes and NASH simultaneously 5

Statins: 2, 5

• Safe and strongly recommended for dyslipidemia management in fatty liver disease 2, 5
• Reduce HCC risk by 37% and hepatic decompensation by 46% 2
• Critical point: Statins are NOT contraindicated in liver disease and should be used aggressively for cardiovascular risk reduction 1, 6

Metformin: 1, 5

• Safe and effective for diabetes management in NAFLD/MAFLD 1
• Does NOT improve liver histology and should not be used as specific NAFLD/MAFLD treatment 5
• Use when eGFR >45 mL/min/1.73 m² 5

Management of Metabolic Comorbidities (Essential for Both Frameworks)

All patients require aggressive treatment of: 1

• Type 2 diabetes (target individualized based on liver function) 1, 5
• Dyslipidemia (statins are first-line) 1, 6
• Hypertension 1
• Cardiovascular disease risk factors (CVD is the leading cause of mortality before cirrhosis develops) 1, 6

Surveillance and Monitoring

For F3-F4 (Advanced Fibrosis/Cirrhosis): 1, 2, 5

• Right upper quadrant ultrasound ± AFP every 6 months for HCC screening 2, 5
• EGD screening for esophageal varices 5
• Liver stiffness ≥20 kPa or thrombocytopenia requires variceal screening 1

For All Patients: 1

• Monitor liver function tests and non-invasive fibrosis markers every 6-12 months depending on fibrosis stage 1

Critical Pitfalls to Avoid

• Never pursue rapid weight loss (>1 kg/week) in patients with advanced liver disease—this can cause acute hepatic failure 1, 5
• Do not withhold statins due to liver disease—they are safe and reduce cardiovascular mortality, which is the primary cause of death in these patients 1, 2, 6
• Pharmacologic therapy should be limited to patients with biopsy-proven NASH and fibrosis or F2+ fibrosis, as those without significant disease have excellent prognosis 5
• No pharmacotherapy is FDA-approved specifically for NAFLD/MAFLD treatment—all current options are off-label 5

Bottom Line

Whether you call it NASH or MAFLD, the management is identical: lifestyle modification forms the foundation for all patients, with pharmacologic therapy reserved for those with significant fibrosis (F2+) or biopsy-proven steatohepatitis, and aggressive treatment of metabolic comorbidities is mandatory to reduce cardiovascular mortality 1, 2, 5.