What are the treatment options for hepatic steatosis?

Treatment Options for Hepatic Steatosis

Lifestyle modifications are the cornerstone of treatment for hepatic steatosis, with Mediterranean diet and regular physical activity being the most effective interventions for improving liver health. 1

Lifestyle Modifications (First-Line Treatment)

Dietary Interventions

• Mediterranean-style diet is strongly recommended:
  • Rich in vegetables, fruits, whole grains, legumes, and healthy fats
  • Daily caloric intake of 1200-1500 kcal
  • Target weight loss of 3-5% to improve steatosis, 7-10% to improve inflammation, and >10% to improve fibrosis 1
  • Replace saturated fats with monounsaturated and polyunsaturated fatty acids 1, 2
  • Use extra virgin olive oil as the primary fat source 1
  • Emphasize omega-3 rich foods 1

Physical Activity

• At least 150-200 minutes/week of moderate-intensity aerobic activities in 3-5 sessions 1
• Combination of aerobic exercise and resistance training is most effective 1
• Exercise can independently reduce hepatic steatosis even without weight loss 3
• Aim for exercise intensity where one can talk but not sing 4

Weight Loss

• Gradual weight loss target of up to 1 kg/week 1
• Hypocaloric diet with 500-1000 kcal daily reduction from baseline 1
• Even modest weight loss (3-5%) can improve steatosis 1

Pharmacological Interventions (Second-Line Treatment)

For Non-Cirrhotic MASH with Significant Fibrosis (Stage ≥2)

• Resmetirom is recommended as first choice due to demonstrated histological efficacy on steatohepatitis and fibrosis 1

For Patients with Diabetes and Hepatic Steatosis

• GLP-1 receptor agonists (e.g., semaglutide) may be considered as adjunctive therapy to lifestyle interventions 1
• SGLT2 inhibitors (e.g., empagliflozin, dapagliflozin) are safe to use but primarily for their indications (type 2 diabetes, heart failure, chronic kidney disease) 1
• Pioglitazone has shown efficacy in reversing steatohepatitis in patients with prediabetes or type 2 diabetes, but is not recommended as specific therapy due to lack of robust histological efficacy evidence 1, 5

For Non-Diabetic Adults with Biopsy-Proven NASH

• Vitamin E (800 IU/day) may be considered, though not recommended as a targeted therapy 1

Surgical Interventions

• Bariatric surgery should be considered for non-cirrhotic MASH in patients meeting approved indications 1
• Has shown improvement in steatosis (91.6%), steatohepatitis (81.3%), and fibrosis (65.5%) 1
• Can induce long-term beneficial liver effects and is associated with remission of type 2 diabetes 1
• For patients with compensated cirrhosis, requires careful evaluation by a multidisciplinary team with experience in bariatric surgery 1

Monitoring and Follow-up

• Liver enzymes: Monitor every 3 months in patients with MASH 1
• Imaging: Repeat at 6-12 months 1
• Liver biopsy: Consider after 1-2 years of therapy to assess histological response 1
• HCC surveillance: Ultrasound examination every 6 months for patients with advanced fibrosis or cirrhosis 1
• Non-invasive fibrosis assessment (e.g., FibroScan, FIB-4): Consider every 1-2 years 1

Important Considerations

• Dietary fat content, independent of caloric intake, is a crucial factor in the development of hepatic steatosis 6
• Even established hepatic steatosis can be reversed by switching to a low-fat diet 6
• Pioglitazone may cause fluid retention, weight gain, and has potential cardiovascular risks 5
• Regular ophthalmologic examinations are recommended for diabetic patients on pioglitazone due to risk of macular edema 5
• Patients on pioglitazone should have liver enzymes monitored before and during treatment 5

Treatment Algorithm

1. Start with intensive lifestyle modifications:

   • Mediterranean diet + regular physical activity
   • Target weight loss of 7-10% of body weight

2. If inadequate response after 6 months:

   • For non-cirrhotic MASH with significant fibrosis: Consider resmetirom
   • For patients with diabetes: Consider GLP-1 receptor agonists
   • For non-diabetic adults with biopsy-proven NASH: Consider vitamin E

3. For patients with obesity meeting criteria for bariatric surgery:

   • Consider bariatric surgery, especially if lifestyle modifications fail

4. Regular monitoring of liver enzymes, imaging, and fibrosis assessment to evaluate treatment response