What is the treatment for steatohepatitis (Non-Alcoholic Steatohepatitis, NASH)?

Treatment of Steatohepatitis (NASH)

Lifestyle modification is the cornerstone of treatment for steatohepatitis, with a target weight loss of 7-10% of body weight to improve liver histology. 1

First-Line Treatment: Lifestyle Modifications

Weight Loss

• Target weight loss of 7-10% of body weight is necessary for histological improvement 2, 1
• Progressive weight loss of less than 1 kg/week is recommended to avoid worsening portal inflammation and fibrosis 2
• Weight reduction correlates significantly with improvement in NASH histological activity score (NAS) 3
• Energy restriction of 500-1000 kcal deficit daily to induce weight loss of 500-1000g/week 1

Dietary Recommendations

• Mediterranean diet pattern is strongly recommended 1
• Focus on:
  • Vegetables, fruits, and fiber-rich foods
  • Limit saturated fats from red and processed meats
  • Minimize or eliminate commercially produced fructose and added sugars
  • Complete alcohol abstinence, especially for those with advanced disease 2, 1
• Protein intake of 1.2-1.5 g/kg body weight, focusing 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 (brisk walking, cycling) and resistance training is effective for improving metabolic risk factors 1

Second-Line Treatment: Pharmacotherapy

For Non-Diabetic Patients with Biopsy-Proven NASH

• Vitamin E (800 IU/day) improves steatosis in NASH patients without diabetes 2, 1
  • Caution: potential concerns about increased all-cause mortality, hemorrhagic stroke, and prostate cancer with long-term use 1

For Patients with Diabetes and NASH

• Pioglitazone is the drug of choice after lifestyle modification fails 2, 1
  • Leads to resolution of steatohepatitis in 47% of patients compared to 21% in placebo groups 2
  • Improves liver histology, including steatosis, inflammation, and ballooning 1
  • Can also reduce cardiovascular disease risk 2

Emerging Therapies

• GLP-1 receptor agonists (semaglutide, tirzepatide) show promise for NASH patients with or without diabetes 1
• Resmetirom is promising for non-cirrhotic patients with significant liver fibrosis (stage ≥2) 1

Not Recommended

• Metformin is not effective for treating NASH despite its use for diabetes 2, 1

Monitoring and Follow-up

Laboratory and Imaging

• 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

For Advanced Disease

• HCC surveillance with ultrasound examination every 6 months for patients with advanced fibrosis or cirrhosis 2, 1
• Aggressive management of comorbidities (diabetes, dyslipidemia, hypertension) 1

Special Considerations

Severe Obesity

• Bariatric surgery may be considered for patients with obesity who cannot achieve adequate weight loss through lifestyle modifications 1
• Surgical weight loss has been shown to improve NASH histology 4

Common Pitfalls to Avoid

1. Underestimating the importance of weight loss - even modest weight loss (5%) can improve steatosis, but 7-10% is needed for histological improvement 1, 3
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

Treatment Algorithm Based on Disease Stage

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