What is the treatment for Non-Alcoholic Fatty Liver Disease (NAFLD)?

Treatment for Non-Alcoholic Fatty Liver Disease (NAFLD)

Weight loss through lifestyle modifications is the cornerstone of treatment for all patients with NAFLD, with a target of 5-10% weight reduction to achieve significant histological improvement. 1

First-Line Treatment: Lifestyle Modifications

Weight Loss Targets

• 3-5% weight loss: Improves hepatic steatosis 2, 1
• 5-7% weight loss: Improves steatosis and inflammation 2, 1
• ≥10% weight loss: Improves fibrosis 2, 1
• Gradual weight loss (<1 kg/week) is recommended to avoid worsening portal inflammation and fibrosis 2, 1

Dietary Recommendations

1. Mediterranean diet pattern is most effective for NAFLD 2, 1

   • Emphasizes vegetables, fruits, whole grains, legumes
   • Olive oil as primary fat source
   • Moderate consumption of fish, white meat, eggs, dairy
   • Limited red meat and processed foods

2. Caloric restriction

   • Daily intake of 1500-1800 kcal for men and 1200-1500 kcal for women 2, 1
   • Reduction of 500-1000 kcal/day from baseline 1
   • Low-carbohydrate diets may be more effective than low-fat diets 2

3. Avoid or minimize:

   • Fructose-enriched soft drinks 2
   • Saturated fats 2, 1
   • Processed foods 1

Exercise Recommendations

• Minimum: 150 minutes per week of moderate-intensity physical activity 2, 1
• Optimal: 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity aerobic exercise weekly 1
• Vigorous exercise (≥6 METs) provides greater benefits for NASH improvement than moderate activity 2, 1
• Resistance training as complementary exercise 1
• Avoid sedentary lifestyle 2

Pharmacological Treatment

Pharmacological treatments should generally be limited to patients with biopsy-proven NASH and fibrosis 2:

1. Vitamin E (800 IU daily)

   • For biopsy-confirmed NASH without diabetes or cirrhosis 2, 1
   • Shown to benefit select patients 2

2. Pioglitazone (30 mg daily)

   • For biopsy-confirmed NASH without cirrhosis 2, 1
   • Effective in patients with or without diabetes 2

3. Emerging therapies (not yet fully approved)

   • GLP-1 receptor agonists (semaglutide, liraglutide) 1, 3, 4
   • SGLT2 inhibitors 1

4. Not recommended for NASH treatment:

   • Metformin (safe for diabetic patients with NAFLD but not effective for liver disease) 2
   • Statins (safe for patients with dyslipidemia but not specifically for NASH) 2

Management of Comorbidities

Aggressive management of metabolic risk factors is essential 2, 1:

• Diabetes
• Hypertension
• Dyslipidemia
• Obesity
• Cardiovascular disease

Monitoring and Follow-up

1. Risk stratification:

   • FIB-4 index for assessing risk of advanced fibrosis 1
   • Transient elastography (FibroScan) for further assessment 1

2. Surveillance:

   • Liver function tests every 3-6 months 1
   • Repeat imaging in 6-12 months 1
   • HCC surveillance with ultrasound every 6 months for patients with advanced fibrosis or cirrhosis 2, 1

Common Pitfalls to Avoid

1. Rapid weight loss (>1.6 kg/week) can worsen liver inflammation and fibrosis 2, 1

2. Focusing only on weight loss without addressing dietary quality 1

3. Neglecting comorbidities that contribute to NAFLD progression 1

4. Excessive alcohol consumption - should be discouraged in NAFLD patients 2, 1

5. Prescribing medications that may worsen steatosis:

   • Corticosteroids
   • Amiodarone
   • Methotrexate
   • Tamoxifen
   • Estrogens
   • Tetracyclines
   • Valproic acid 2

The combined approach of diet and exercise is superior to either intervention alone in improving liver enzymes and insulin resistance 5. Sustained lifestyle changes remain the most effective treatment for NAFLD, with pharmacotherapy reserved for those with biopsy-proven NASH and fibrosis.