What are the causes and treatment options for hepatic steatosis?

Causes and Treatment of Hepatic Steatosis

The primary treatment for hepatic steatosis (fatty liver) should be lifestyle modifications focusing on weight loss of 7-10% through dietary changes and regular physical exercise, as this has been proven to improve liver histology and reduce liver fat. 1, 2

Causes of Hepatic Steatosis

Hepatic steatosis occurs when there is excessive accumulation of fat in the liver cells. Common causes include:

• Metabolic factors:

  • Obesity
  • Type 2 diabetes
  • Insulin resistance
  • Dyslipidemia
  • Metabolic syndrome

• Dietary factors:

  • Excessive caloric intake
  • High consumption of ultra-processed foods
  • Sugar-sweetened beverages
  • High fructose intake
  • Excessive alcohol consumption

• Lifestyle factors:

  • Physical inactivity
  • Sedentary behavior

• Other causes:

  • Certain medications
  • Rapid weight loss
  • Malnutrition
  • Genetic predisposition

Treatment Approach

1. Lifestyle Modifications (First-Line Treatment)

Diet Recommendations:

• Mediterranean dietary pattern is strongly recommended 1, 2
• Limit consumption of ultra-processed foods rich in sugars and saturated fat
• Avoid sugar-sweetened beverages
• Caloric restriction of 500-1000 kcal energy deficit daily 2
• Minimum protein intake of 1.2-1.5 g/kg body weight 2
• Complete alcohol abstinence 2

Weight Loss Targets:

• >5% weight loss to reduce liver fat
• 7-10% weight loss to improve liver inflammation
• >10% weight loss to improve fibrosis 1
• Weight loss rate should be <1 kg/week to avoid worsening portal inflammation 2

Physical Activity:

• At least 150 minutes/week of moderate-intensity aerobic activity or 75 minutes/week of vigorous-intensity physical activity 1, 2
• Combination of aerobic exercise and resistance training is effective 2
• Exercise alone (without dietary changes) has been shown to reduce liver fat by approximately 2.4% 3

2. Pharmacological Interventions

For patients with significant fibrosis (stage ≥2):

• Resmetirom is recommended as first choice for non-cirrhotic MASLD with significant liver fibrosis due to its demonstrated histological efficacy 2

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

  • Safe to use in MASLD including compensated cirrhosis
  • Indicated for type 2 diabetes and obesity
  • Can provide substantial weight loss with potential hepatic histological benefit 2

• SGLT2 inhibitors (empagliflozin, dapagliflozin):

  • Safe to use in MASLD
  • Should be used for their primary indications (type 2 diabetes, heart failure, chronic kidney disease)
  • Insufficient evidence to recommend specifically for MASLD 2

• Metformin:

  • Can be used with compensated cirrhosis if GFR >30 ml/min
  • Not recommended specifically for liver disease in NASH 2

3. Surgical Interventions

• Bariatric surgery:
  • Should be considered for non-cirrhotic MASLD with approved indications
  • Can induce long-term beneficial liver effects
  • Associated with remission of type 2 diabetes and improvement of cardiometabolic risk factors 2
  • For compensated cirrhosis, requires careful evaluation by a multidisciplinary team 2

Monitoring and Follow-Up

• Non-invasive fibrosis assessment (FibroScan, FIB-4) every 1-2 years to monitor disease progression 2
• Liver enzymes should be monitored every 3 months 2
• Imaging should be repeated at 6-12 months 2
• Liver biopsy is not suited for routine monitoring due to invasiveness but can be considered in specific cases 1
• HCC surveillance with ultrasound examination every 6 months for patients with advanced fibrosis or cirrhosis 2

Important Considerations

• A multidisciplinary approach is strongly recommended to address both liver-related and extrahepatic outcomes 1
• Nutraceuticals cannot be recommended due to insufficient evidence of effectiveness 1, 2
• Patients with F0-F2 fibrosis who maintain stable disease can be followed in primary care 2
• Aggressively manage comorbid metabolic conditions (diabetes, hypertension, dyslipidemia) to prevent disease progression 2

Treatment Algorithm

1. Assess fibrosis stage using non-invasive tests
2. For all patients: Implement lifestyle modifications (diet, exercise, weight loss)
3. For patients with significant fibrosis (≥F2):
   • Continue lifestyle modifications
   • Consider pharmacotherapy (resmetirom as first choice)
   • Consider bariatric surgery if appropriate
4. For patients with advanced fibrosis/cirrhosis:
   • All of the above
   • Add HCC surveillance
   • Careful medication selection

Exercise has been shown to effectively reduce hepatic steatosis independent of changes in body mass 4, making it a crucial component of treatment even when weight loss is challenging.