What are the treatment options for hepatic steatosis?

Treatment Options for Hepatic Steatosis

The cornerstone of hepatic steatosis treatment is lifestyle modification with a target weight loss of 7-10% of body weight, achieved through a Mediterranean diet pattern and regular physical activity of 150-200 minutes per week. 1

First-Line Treatment: Lifestyle Modifications

Dietary Recommendations

• Mediterranean diet pattern is strongly recommended, focusing on:
  • Vegetables, fruits, and fiber-rich foods
  • Limited saturated fats
  • Minimal commercially produced fructose and added sugars
  • Complete alcohol abstinence (especially for advanced disease) 1, 2
• Energy restriction of 500-1000 kcal deficit daily to induce weight loss of 500-1000g/week 1
• Minimum protein intake of 1.2-1.5 g/kg body weight, with focus on branched-chain amino acids 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 for improving metabolic risk factors 1, 3
• Exercise can effectively reduce hepatic steatosis independent of changes in body mass 3

Pharmacotherapy (When Lifestyle Modifications Fail)

Based on Disease Stage

1. NAFL or NASH with fibrosis stage 0-1: Lifestyle modifications only 1
2. NASH with fibrosis stage 2-3: Lifestyle modifications plus pharmacotherapy 1
3. NASH cirrhosis: Lifestyle modifications plus individualized pharmacotherapy with close monitoring 1

Medication Options

• Pioglitazone: First-line pharmacotherapy when lifestyle modification fails

  • Leads to resolution of steatohepatitis in 47% of patients compared to 21% in placebo groups
  • Improves liver histology and reduces cardiovascular disease risk 1

• Vitamin E (800 IU/day):

  • Improves steatosis in NASH patients without diabetes
  • Caution advised due to potential concerns about increased all-cause mortality, hemorrhagic stroke, and prostate cancer with long-term use 1

• GLP-1 receptor agonists (semaglutide and tirzepatide):

  • Shown to improve liver histology in NASH patients
  • Particularly effective for patients with comorbid type 2 diabetes or obesity 1

• Resmetirom:

  • Most promising MASH-targeted pharmacological therapy for non-cirrhotic patients with significant liver fibrosis (stage ≥2)
  • Shows histological effectiveness on steatohepatitis and fibrosis with acceptable safety profile 1

• Not recommended:

  • Metformin: Not effective for treating NASH despite its use for diabetes 1
  • Nutraceuticals: Insufficient evidence on effectiveness and safety 1

Surgical Options

• Bariatric surgery: Consider for patients with obesity and hepatic steatosis who fail to respond to lifestyle interventions 1

Monitoring and Follow-up

• HCC surveillance with ultrasound examination every 6 months for patients with advanced fibrosis or cirrhosis 1
• Monitor liver enzymes every 3 months 1
• Repeat imaging at 6-12 months 1
• Consider repeat biopsy after 1-2 years of therapy to assess histological response 1
• Aggressive management of comorbidities (diabetes, dyslipidemia, hypertension) 1

Common Pitfalls to Avoid

1. Underestimating weight loss importance: Even modest weight loss (5%) improves 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. Focusing only on caloric restriction: Dietary fat content, independent from caloric intake, is crucial in the development of hepatic steatosis 4
5. Neglecting physical activity: Exercise can independently improve steatosis, prevent fibrosis and cirrhosis, and reduce mortality 3