What are the treatment options for fatty liver disease (Non-Alcoholic Fatty Liver Disease (NAFLD))?

Treatment Options for Non-Alcoholic Fatty Liver Disease (NAFLD)

Lifestyle modifications, including weight loss through diet and exercise, are the cornerstone of treatment for all patients with NAFLD, with pharmacotherapy reserved for those with biopsy-proven NASH and fibrosis. 1, 2

First-Line Treatment: Lifestyle Modifications

Weight Loss Goals

• For overweight/obese patients, aim for 7-10% weight loss, which significantly improves liver histology, reduces steatosis, inflammation, and can reverse NASH 2, 3
• Even modest weight loss (5-7%) can improve hepatic steatosis and components of the NAFLD activity score 1
• For non-obese individuals with NAFLD, a more modest 3-5% weight loss can achieve NAFLD remission 1
• Weight loss should be gradual (maximum 1 kg/week) as rapid weight loss can worsen portal inflammation and fibrosis 1

Dietary Recommendations

• Mediterranean diet pattern is most strongly recommended, even without weight loss it can reduce liver fat content 2, 4
• Reduce total caloric intake by 500-1000 kcal/day 2
  • Men: 1,500-1,800 kcal/day
  • Women: 1,200-1,500 kcal/day 1
• Reduce carbohydrate intake, especially sugars and refined carbohydrates 1, 2
• Limit or avoid fructose and sugar-sweetened beverages 1, 2
• Replace saturated fats with monounsaturated and omega-3 fatty acids 2, 4

Physical Activity

• Aim for at least 150-300 minutes of moderate-intensity aerobic exercise per week 2
• Include resistance training as a complement to aerobic exercise 2
• Exercise alone, even without weight loss, can decrease liver fat content by improving insulin sensitivity 2, 5
• Vigorous exercise (≥6 METs) is associated with lower frequency of NASH and advanced fibrosis 1

Pharmacological Treatment for NASH

For Non-Diabetic Patients with Biopsy-Proven NASH

• Vitamin E (800 IU/day) improves liver histology through antioxidant properties 1, 2, 3
• Caution with long-term vitamin E use due to potential increased risk of all-cause mortality, hemorrhagic stroke, and prostate cancer 1, 2

For Patients with Biopsy-Proven NASH (With or Without Diabetes)

• Pioglitazone (30 mg daily) improves all histological features except fibrosis 1, 2, 3
• Side effects include weight gain, bone fractures in women, and rarely congestive heart failure 1, 2

Emerging Treatments

• GLP-1 receptor agonists show promise for NASH treatment, though evidence is still emerging 2, 3, 6
• SGLT2 inhibitors may be beneficial but require further investigation 1

Treatment Algorithm Based on Disease Severity

For NAFL (Simple Steatosis) or NASH with Minimal Fibrosis (F0-F1)

• Focus on lifestyle modifications only (diet, exercise, weight loss) 2
• Treat comorbidities (diabetes, hypertension, dyslipidemia) 2
• Monitor for disease progression with periodic non-invasive testing 2

For NASH with Significant Fibrosis (F2-F3)

• Intensive lifestyle modifications 2
• Consider pharmacotherapy:
  • Non-diabetic patients: Vitamin E 800 IU/day 1, 2
  • Diabetic patients: Pioglitazone 30 mg daily 1, 2

For NASH with Cirrhosis (F4)

• Lifestyle modifications with careful monitoring 2
• Limited evidence for pharmacotherapy 2
• Hepatocellular carcinoma surveillance with ultrasound ± AFP every 6 months 2

Common Pitfalls and Caveats

• Avoid rapid weight loss (>1 kg/week) as it may worsen liver disease 1, 2
• Sustainability is key - choose dietary and exercise regimens that can be maintained long-term 2
• No specific pharmacotherapy has been approved by regulatory agencies specifically for NAFLD treatment 2
• Metformin is not recommended as a specific treatment for NAFLD as it has no significant effect on liver histology 2
• Bariatric surgery can be considered for eligible patients with obesity, showing improvement in liver fat, inflammation, and fibrosis 7, 8