What are the treatment options for hepatic steatosis?

Treatment Options for Hepatic Steatosis

Lifestyle modifications are the cornerstone of treatment for hepatic steatosis, with a 7-10% weight loss being the primary target for overweight/obese patients to improve liver enzymes and reduce hepatic fat. 1

First-Line Treatment: Lifestyle Modifications

Diet Recommendations

• Mediterranean diet is strongly recommended with high-quality evidence 1
  • Reduce caloric intake by 30% or approximately 750-1,000 kcal/day
  • Focus on vegetables, fruits, whole grains, lean proteins
  • Minimize refined carbohydrates, processed foods, and saturated fats
• Avoid fructose and sugar-sweetened beverages which can exacerbate hepatic steatosis 1
• Maintain adequate protein intake (1.2-1.5 g/kg body weight/day) to prevent sarcopenia, especially important in advanced disease 1

Exercise Recommendations

• Both aerobic exercise and resistance training are effective in reducing liver fat 1
• Aim for at least 150-300 minutes of moderate-intensity exercise or 75-150 minutes of vigorous-intensity exercise weekly
• Include muscle-strengthening activities to improve lean body mass
• Vigorous activity (≥6 METs) shows greater benefit for improving steatohepatitis than moderate activity 1
• Exercise alone can reduce hepatic steatosis even without significant weight loss 1, 2

Second-Line Treatment: Pharmacological Options

Pharmacological treatments should generally be limited to those with biopsy-proven NASH and fibrosis 1:

For Patients with Diabetes and Hepatic Steatosis

• GLP-1 receptor agonists can be considered for patients with Child-Pugh class A cirrhosis 1
• SGLT2 inhibitors can be used in patients with Child-Pugh class A and B cirrhosis 1
• Metformin can be used in compensated cirrhosis with preserved renal function (avoid in decompensated cirrhosis) 1
• Pioglitazone may be considered for patients with biopsy-confirmed NASH with or without diabetes, but with caution due to potential side effects including weight gain, peripheral edema, heart failure, and fractures 1, 3

For Non-Diabetic Patients

• Vitamin E may be considered for non-diabetic patients with biopsy-confirmed NASH without cirrhosis, but with caution due to potential side effects including increased risk of prostate cancer and all-cause mortality 1
• Statins can be used in chronic liver disease including compensated cirrhosis to reduce cardiovascular events 1

Monitoring and Assessment

Initial Assessment

• Baseline assessment should include liver enzymes, complete blood count, coagulation profile, and renal function 1
• Consider liver biopsy if the patient has risk factors for metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis, or if findings are concerning for cirrhosis 1

Follow-up Monitoring

• Monitor liver enzymes every 3-6 months 1
• Fibrosis assessment should be repeated every 1-2 years based on initial risk 1
• Fib-4 score < 1.3 reliably excludes advanced fibrosis with a negative predictive value ≥90% 1
• Reassess Fib-4 score in 1-3 years given a low baseline value 1
• Monitor liver enzymes and repeat imaging (ultrasound or controlled attenuation parameter) after 3-6 months of intervention 1

Special Considerations

Bariatric Surgery

• Consider for patients with obesity and hepatic steatosis who have not responded to lifestyle interventions 1

Hepatotoxicity Monitoring

• When using medications like pioglitazone, monitor for potential hepatotoxicity
• Evaluate ALT levels prior to initiating therapy and periodically thereafter 3
• If ALT levels exceed 3 times the upper limit of normal, the medication should be discontinued 3

Cautions with Pioglitazone

• May cause weight gain, peripheral edema, heart failure, and fractures 1, 3
• Increased risk of bone fractures, particularly in female patients 3
• May result in ovulation in some premenopausal anovulatory women 3

Treatment Algorithm

1. Start with lifestyle modifications for all patients with hepatic steatosis
2. Assess response after 3-6 months with liver enzymes and imaging
3. If inadequate response and biopsy-proven NASH with fibrosis:
   • Consider pharmacological therapy based on patient characteristics
   • For diabetic patients: Consider GLP-1 agonists, SGLT2 inhibitors, or pioglitazone
   • For non-diabetic patients: Consider vitamin E
4. For patients with obesity who fail lifestyle interventions: Consider bariatric surgery
5. Monitor regularly with liver enzymes every 3-6 months and fibrosis assessment every 1-2 years