What are the management options for Non-Alcoholic Fatty Liver Disease (NAFLD)?

Management of Non-Alcoholic Fatty Liver Disease (NAFLD)

The cornerstone of NAFLD management is lifestyle modification with weight loss of 7-10% to improve liver histology, while pharmacological treatments should be limited to patients with biopsy-proven NASH and fibrosis. 1, 2

Risk Stratification

Before initiating treatment, assess fibrosis risk:

• Low risk: FIB-4 <1.3 or FibroScan <8 kPa
• Indeterminate risk: FIB-4 1.3-2.67 or FibroScan 8-12 kPa
• High risk: FIB-4 >2.67 or FibroScan >12 kPa 2

Low-risk patients should be reassessed after 3 years, while higher-risk patients require more frequent monitoring and possible specialist referral.

Lifestyle Modifications

Weight Loss Targets

• 5% weight loss: Improves hepatic steatosis
• 7% weight loss: Improves NAFLD Activity Score
• ≥10% weight loss: Can induce near-universal NASH resolution and fibrosis improvement 1, 2

Diet Recommendations

• Caloric restriction: 750-1,000 kcal/day reduction from baseline
• Mediterranean diet pattern: Emphasizing vegetables, fruits, whole grains, legumes, olive oil, moderate fish, and limited red meat 2, 3
• Carbohydrate modifications: Reduce simple carbohydrates and fructose; avoid sugar-sweetened beverages 2

Physical Activity

• Frequency: At least 3 times per week
• Duration: Minimum 30 minutes per session
• Intensity: Moderate to vigorous (≥6 METs for fibrosis improvement)
• Type: Both aerobic activity and resistance training are effective 2, 4

Pharmacological Interventions

Pharmacological treatments should be limited to patients with biopsy-proven NASH and fibrosis 1:

For NASH Patients with Diabetes

• GLP-1 receptor agonists:
  • Semaglutide: Titrate to 1 mg weekly (strongest evidence for histological benefit)
  • Liraglutide: Shown to reverse steatohepatitis and reduce fibrosis progression 2
• SGLT2 Inhibitors: Improve glucose control and cardiometabolic profile 2

For Non-diabetic NASH Patients without Cirrhosis

• Vitamin E: 800 IU/day - improves steatosis, inflammation, and ballooning 2

For NASH Patients with or without Diabetes (without Cirrhosis)

• Pioglitazone: 30 mg/day - improves all histological features except fibrosis 2

Special Considerations

• Alcohol: Complete restriction is recommended as even low intake doubles the risk of adverse liver outcomes 2
• Cardiovascular risk: Patients should be educated about the strong association between NAFLD and cardiovascular disease 2
• Diabetes management: Optimize diabetes control in affected patients 2
• Nutritional consultation: Strongly recommended, especially for patients with sarcopenia 2
• Bariatric surgery: Consider for obese patients with NAFLD/NASH if otherwise indicated 2

Monitoring

• Monitor liver enzymes, metabolic parameters, and weight at regular intervals
• Reassess fibrosis risk using non-invasive tests periodically based on initial risk stratification
• For patients on pharmacotherapy, monitor for medication-specific adverse effects

Common Pitfalls and Caveats

• Metformin: Has no significant effect on liver histology and is not recommended as a specific treatment for liver disease in adults with NASH 1
• GLP-1 RAs: Common adverse effects include nausea, constipation, and vomiting; no GLP-1 RA is currently FDA-approved specifically for NAFLD/NASH 2
• Silymarin: Not currently recommended as primary treatment due to insufficient evidence 2
• Exercise alone: May reduce hepatic steatosis but its effect on other aspects of liver histology remains unclear without dietary intervention 1