What is the treatment for hepatic (liver) steatosis?

Treatment of Hepatic Steatosis

The primary treatment for hepatic steatosis (MASLD/NAFLD) is lifestyle modification with a goal of weight loss through dietary changes and increased physical activity, targeting 3-5% weight loss to improve steatosis, 7-10% to improve inflammation, and >10% to improve fibrosis. 1, 2

Lifestyle Modifications

Weight Loss Targets

• 3-5% weight loss: Improves hepatic steatosis
• 7-10% weight loss: Improves liver inflammation and NASH
• >10% weight loss: Improves fibrosis and can lead to NASH resolution

Dietary Recommendations

1. Mediterranean diet pattern is most strongly recommended 1, 2, 3

   • High in vegetables, fruits, whole grains, olive oil
   • Moderate fish and white meat consumption
   • Limited red and processed meat

2. Specific dietary restrictions:

   • Limit ultra-processed foods high in sugars and saturated fats
   • Avoid sugar-sweetened beverages
   • Replace saturated fats with polyunsaturated and monounsaturated fatty acids
   • Limit excess fructose consumption 1, 2

3. Caloric restriction:

   • Hypocaloric diet (500-1000 kcal/day deficit) to achieve weight loss goals

Physical Activity

• Minimum recommendation: 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous-intensity physical activity 1, 2
• Exercise alone can reduce hepatic steatosis even without significant weight loss 1, 2
• Both aerobic and resistance training are beneficial
• Tailor exercise to individual preferences and capabilities to improve adherence

Pharmacological Treatment Options

First-line Medications

• Resmetirom may be considered for adults with non-cirrhotic steatohepatitis and significant hepatic fibrosis (stage ≥2) if locally approved 1, 2

Other Medications

• GLP-1 receptor agonists (semaglutide, liraglutide) are not specifically recommended for steatohepatitis alone but can provide indirect hepatic benefits through weight loss in patients with obesity or type 2 diabetes 2
• Metformin has no significant effect on liver histology and is not recommended as a specific treatment for liver disease in NASH 1
• Vitamin E is not recommended as a targeted therapy for steatohepatitis due to lack of robust demonstration of histological efficacy and potential long-term risks 2
• Pioglitazone is safe in adults with non-cirrhotic steatohepatitis but has limited evidence for histological efficacy 2, 4

Special Considerations

Alcohol Consumption

• Complete abstinence from alcohol is recommended for patients with advanced fibrosis or cirrhosis
• Significant limitation of alcohol consumption is recommended for all other patients with hepatic steatosis 2

Monitoring Response to Treatment

• Follow-up with non-invasive tests (liver enzymes, imaging techniques) after 3-6 months of lifestyle intervention
• Liver biopsy is not suited for routine monitoring due to invasiveness 1
• Non-invasive monitoring using:
  • Liver enzymes (ALT, AST)
  • Imaging techniques: ultrasound, Controlled Attenuation Parameter (CAP), or MRI-Proton Density Fat Fraction (MRI-PDFF)

Common Pitfalls to Avoid

1. Focusing only on liver enzymes - normal enzymes don't exclude significant liver disease
2. Ignoring cardiovascular risk - cardiovascular disease is the main driver of morbidity and mortality before development of cirrhosis
3. Rapid weight loss - can potentially worsen liver inflammation; gradual, sustained weight loss is preferred
4. Poor follow-up - inadequate monitoring and lack of sustained adherence to lifestyle changes is a major barrier to success
5. Relying on supplements or nutraceuticals - insufficient evidence for their effectiveness and safety 2

Treatment Algorithm

1. Initial approach: Lifestyle modification with dietary changes and increased physical activity
2. If BMI >30 with comorbidities: Consider GLP-1 agonists for weight loss
3. If non-cirrhotic MASH with fibrosis stage ≥2: Consider resmetirom if available
4. If significant obesity (BMI >35 with comorbidities or >40): Consider bariatric surgery evaluation

The evidence consistently shows that lifestyle modification with weight loss is the cornerstone of treatment for hepatic steatosis, with pharmacological options playing a supportive role in specific patient populations.