What are the treatment options for hepatic steatosis?

Treatment Options for Hepatic Steatosis

Lifestyle modification is the cornerstone of treatment for hepatic steatosis, with a target weight loss of 7-10% of body weight to improve liver histology. 1

First-Line Treatment: Lifestyle Modifications

Dietary Interventions

• Mediterranean diet pattern is strongly recommended, emphasizing:
  • Vegetables, fruits, and fiber-rich foods
  • Limited saturated fats, processed meats, and simple sugars
  • Complete alcohol abstinence (especially for advanced disease) 1
• Caloric restriction of 500-1000 kcal energy deficit to induce weight loss of 500-1000g/week 1
• Avoid or limit:
  • Fructose-containing beverages and foods
  • Processed foods high in added sugars
  • Saturated fatty acids from red and processed meats 1
• Ensure minimum protein intake of 1.2-1.5 g/kg body weight, focusing on branched-chain amino acids 1
• Consider consultation with a specialized nutritionist 1

Physical Activity

• At least 150-200 minutes/week of moderate-intensity aerobic activities in 3-5 sessions 1
• Both aerobic exercise (brisk walking, stationary cycling) and resistance training are effective for improving metabolic risk factors 1
• Target physical activity level where one can talk but not sing 2

Second-Line Treatment: Pharmacotherapy

When lifestyle modifications fail to achieve adequate improvement, consider:

For Biopsy-Proven NASH:

• Pioglitazone is the drug of choice after lifestyle modification fails, particularly for patients with biopsy-proven NASH (Grade 1A evidence) 1
  • Significantly improves liver histology, including steatosis, inflammation, and ballooning
• Vitamin E (800 IU/day) is an alternative for non-diabetic patients with biopsy-proven NASH
  • Caution: potential concerns about increased all-cause mortality, hemorrhagic stroke, and prostate cancer with long-term use 1

For Patients with Comorbidities:

• GLP-1 receptor agonists (semaglutide, tirzepatide) for patients with comorbid type 2 diabetes or obesity
  • Shown to improve liver histology in NASH patients with or without diabetes 1
• Resmetirom for non-cirrhotic patients with significant liver fibrosis (stage ≥2)
  • Most promising MASH-targeted therapy showing histological effectiveness on steatohepatitis and fibrosis 1

Not Recommended:

• Metformin is not recommended for NASH treatment despite its use for diabetes
  • No significant effect on liver histology (Grade 1A evidence against its use) 1
• Nutraceuticals are not recommended due to insufficient evidence on effectiveness and safety 1

Monitoring and Follow-up

Regular Assessment:

• Monitor liver enzymes every 3 months 1
• Repeat imaging at 6-12 months 1
• Ultrasound examination every 6 months 1
• Consider repeat biopsy after 1-2 years of therapy to assess histological response 1

For Advanced Disease:

• HCC surveillance every 6 months for patients with advanced fibrosis or cirrhosis 1
• Referral to a hepatologist for multidisciplinary management 1
• Aggressive management of diabetes, dyslipidemia, hypertension, and cardiovascular disease 1

Common Pitfalls to Avoid

1. Underestimating weight loss importance: Even modest weight loss (5%) can improve steatosis, but 7-10% is needed for histological improvement 1

2. Prescribing medications without biopsy confirmation: Vitamin E and Pioglitazone should be restricted to patients with biopsy-confirmed NASH 1

3. Allowing alcohol consumption: Even moderate alcohol use can double the risk of adverse liver-related outcomes 1

4. Relying solely on liver enzymes: Non-invasive monitoring methods like controlled attenuation parameter (CAP) and magnetic resonance imaging-proton density fat fraction (MRI-PDFF) are more accurate for tracking changes in hepatic steatosis 3

5. Focusing only on the liver: NAFLD is associated with increased mortality from cardiovascular disease and extrahepatic cancers, requiring a comprehensive approach 2