What are the treatment options for hepatic steatosis?

Treatment Options for Hepatic Steatosis

The cornerstone of treatment for hepatic steatosis is lifestyle modification, including a Mediterranean-style diet and regular physical activity, with weight loss of 7-10% being the most effective intervention for improving liver inflammation and biochemistry. 1

First-Line Treatment: Lifestyle Modifications

Dietary Recommendations

• Mediterranean-style diet is the most evidence-based dietary approach 1, 2:
  • Rich in vegetables, fruits, whole grains, legumes, and healthy fats
  • Daily caloric intake of 1200-1500 kcal
  • Replace saturated fats with monounsaturated and polyunsaturated fatty acids
  • Emphasize omega-3 rich foods and extra virgin olive oil as primary fat source
  • Minimum protein intake of 1.2-1.5 g/kg body weight
  • Reduce consumption of ultra-processed foods, red meat, and sugar-sweetened beverages 3

Weight Loss Targets

• Gradual weight loss goals 1:
  • 3-5% to improve steatosis
  • 7-10% to improve liver inflammation and biochemistry

  • 10% to improve fibrosis

  • Target rate of 1 kg/week through hypocaloric diet (500-1000 kcal daily reduction)

Physical Activity

• Exercise recommendations 1, 4:
  • 150-200 minutes/week of moderate-intensity aerobic activities
  • Divide into 3-5 sessions per week
  • Combine aerobic exercise with resistance training
  • Exercise independently improves steatosis, prevents fibrosis, and reduces mortality 4

Pharmacological Interventions

First-Choice Medication

• Resmetirom is recommended as first choice for non-cirrhotic MASH with significant liver fibrosis (stage ≥2) 1
  • Demonstrated histological efficacy on steatohepatitis and fibrosis
  • Acceptable safety and tolerability profile

Other Medication Options

• GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide) 1:

  • Safe to use in MASH, including compensated cirrhosis
  • Primarily indicated for type 2 diabetes and obesity
  • Substantial weight loss provides potential hepatic histological benefit

• SGLT2 inhibitors (empagliflozin, dapagliflozin) 1:

  • Safe to use in MASH
  • Should be used for their primary indications (type 2 diabetes, heart failure, chronic kidney disease)
  • Insufficient evidence to recommend as MASH-targeted therapy

• Metformin 1:

  • Can be used with compensated cirrhosis if GFR >30 ml/min
  • Not recommended specifically for liver disease in NASH

• Pioglitazone 1, 5:

  • Not recommended as a specific therapy due to lack of robust demonstration of histological efficacy
  • Has potential side effects including weight gain, edema, heart failure, bone fractures (especially in women), and macular edema 5

Bariatric Surgery

• Consider for non-cirrhotic MASH with approved indications 1:
  • Can induce long-term beneficial liver effects
  • Associated with remission of type 2 diabetes
  • Improves cardiometabolic risk factors
  • For compensated cirrhosis, requires careful evaluation by a multidisciplinary team

Monitoring and Follow-up

• Laboratory monitoring 1:

  • Liver enzymes every 3 months
  • For patients on pioglitazone: monitor liver enzymes prior to initiation and periodically thereafter 5

• Imaging 1:

  • Repeat at 6-12 months
  • HCC surveillance with ultrasound examination every 6 months for patients with advanced fibrosis or cirrhosis

• Non-invasive fibrosis assessment 1:

  • FibroScan, FIB-4 every 1-2 years to monitor for disease progression

• Liver biopsy 1:

  • Consider after 1-2 years of therapy to assess histological response

Common Pitfalls and Caveats

• Rapid weight loss can worsen liver disease; gradual weight loss is safer 1
• Sustained adherence to lifestyle modifications is more important than specific macronutrient composition 1
• Patients with diabetes should have regular eye exams by an ophthalmologist, especially if on thiazolidinediones like pioglitazone 5
• Women on pioglitazone have increased risk of bone fractures, particularly non-vertebral fractures 5
• Dietary fat content, independent of caloric intake, is a crucial factor in the development of hepatic steatosis 6
• No pharmacological treatments have conclusively demonstrated macrovascular risk reduction 5