What medications are used to treat fatty liver disease, specifically non-alcoholic fatty liver disease (NAFLD)?

Medications for Non-Alcoholic Fatty Liver Disease (NAFLD)

For non-alcoholic fatty liver disease (NAFLD), lifestyle modifications remain the first-line treatment, while pharmacotherapy should be reserved for patients with non-alcoholic steatohepatitis (NASH), especially those with fibrosis or at high risk of fibrosis progression. 1

First-Line Treatment: Lifestyle Modifications

Lifestyle interventions should be the initial approach for all NAFLD patients:

• Weight loss targets:

  • Progressive weight loss of <1 kg/week
  • Target 7-10% weight loss for histologic improvement including fibrosis regression 1
  • For lean NAFLD patients (BMI <25 kg/m² for non-Asians or <23 kg/m² for Asians), a more modest 3-5% weight loss is suggested 2

• Dietary recommendations:

  • Mediterranean diet or low-carbohydrate/low-fructose diet
  • Increased consumption of monounsaturated fats, omega-3 fats, plant-based proteins, and dietary fibers
  • Avoidance of processed foods, foods high in added fructose, saturated fatty acids, and trans fats 1
  • Avoidance of sugar-sweetened drinks 2

• Exercise recommendations:

  • At least moderate-intensity exercise for >30 minutes, >3 times per week
  • Combination of aerobic exercise and resistance training 1

Pharmacotherapy Options

Pharmacotherapy should be considered for:

• Patients with biopsy-proven NASH
• Patients with fibrosis or at high risk of fibrosis progression
• Risk factors include: age >50 years, diabetes, metabolic syndrome, and elevated ALT 1

FDA-Approved Medications for NAFLD/NASH

Currently, no medications have FDA approval specifically for NAFLD treatment. However, the following medications have evidence supporting their use:

1. Vitamin E (800 IU/day):

   • Recommended for: Non-diabetic NASH patients without cirrhosis
   • Benefits: Improves steatosis, inflammation, and ballooning
   • Cautions: Safety concerns with long-term use include increased risk of hemorrhagic stroke and prostate cancer in males older than 50 1
   • In children with biopsy-proven NASH, vitamin E showed statistically significant improvements in NAS and resolution of NASH compared to placebo 2

2. Pioglitazone (30 mg/day):

   • Recommended for: NASH patients with or without diabetes (without cirrhosis)
   • Benefits: Improves all histological features except fibrosis
   • Side effects: Weight gain, bone fractures, peripheral edema, and heart failure 1

3. GLP-1 Receptor Agonists:

   • Recommended for: NAFLD patients with diabetes
   • Benefits: Improve cardiometabolic profile and reverse steatosis
   • Note: Their therapeutic role in lean NAFLD requires further investigation 2, 1

4. SGLT2 Inhibitors:

   • Recommended for: NAFLD patients with diabetes
   • Benefits: Improve glucose control and cardiometabolic profile
   • Note: Like GLP-1 agonists, their role in lean NAFLD needs further investigation 2, 1

Medications Not Recommended

1. Metformin:
   • Not recommended for children with NAFLD at 500 mg twice daily as it showed no effect on liver biochemistries or histology 2
   • Not specifically recommended for adults with NAFLD in current guidelines

Special Considerations

For Lean NAFLD Patients

• Lifestyle intervention targeting modest weight loss (3-5%)
• Exercise and diet modification
• Avoidance of fructose and sugar-sweetened drinks
• Vitamin E may be considered in those with biopsy-confirmed NASH without diabetes or cirrhosis
• Pioglitazone 30 mg daily may be considered in those with biopsy-confirmed NASH with or without diabetes but without cirrhosis 2

For Children with NAFLD

• Intensive lifestyle modification improves aminotransferases and liver histology
• Vitamin E 800 IU/day offers histological benefits to children with biopsy-proven NASH
• Metformin at 500 mg twice daily is not recommended 2

Monitoring and Risk Stratification

• Use non-invasive tests (FIB-4 index, transient elastography) to assess fibrosis stage
• Consider liver biopsy for patients with increased risk of steatohepatitis and advanced fibrosis
• For patients with NAFLD-associated cirrhosis, HCC surveillance is recommended 1

The treatment of NAFLD remains challenging due to limited pharmacological options, making lifestyle modifications the cornerstone of management. Pharmacotherapy should be tailored based on the presence of NASH, fibrosis stage, and comorbidities such as diabetes.