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

Treatment for NASH

Lifestyle modification targeting 7-10% weight loss through Mediterranean diet and regular exercise is the cornerstone of NASH treatment, with pharmacotherapy (vitamin E for non-diabetics, pioglitazone for diabetics) reserved exclusively for biopsy-proven NASH with significant fibrosis (≥F2). 1, 2

Risk Stratification Determines Treatment Approach

Your treatment intensity depends entirely on fibrosis stage:

• F0-F1 (minimal fibrosis): Lifestyle modifications ONLY—no pharmacotherapy indicated 1, 2
• F2-F3 (significant fibrosis): Intensive lifestyle modifications PLUS pharmacotherapy 1, 2
• F4 (cirrhosis): Lifestyle modifications with careful monitoring, limited pharmacotherapy evidence, and mandatory HCC surveillance with ultrasound ± AFP every 6 months 1

Patients with FIB-4 >2.67, liver stiffness >12.0 kPa by transient elastography, or biopsy-proven clinically significant fibrosis require hepatologist-coordinated multidisciplinary care 2

Lifestyle Modifications: The Non-Negotiable Foundation

Weight Loss Targets

• 7-10% weight loss significantly improves liver histology, reduces steatosis and inflammation, and can reverse NASH 1, 2
• >10% weight loss induces near-universal NASH resolution and fibrosis improvement by at least one stage 3
• Even 5-7% weight loss improves hepatic steatosis and components of the NAFLD activity score 1
• Aim for gradual weight loss of 0.5-1 kg/week to avoid rapid reduction that may worsen liver disease 4
• Structured weight loss programs are superior to general education alone, with two-thirds of patients in intensive intervention no longer meeting NASH criteria after 48 weeks 1

Dietary Modifications

Mediterranean diet is the most strongly recommended dietary pattern 1, 2:

• Reduced carbohydrate intake (40% of calories vs. 50-60% in typical low-fat diet) 3
• Increased monounsaturated and omega-3 fatty acids (40% of calories as fat) 3
• Rich in fruits, vegetables, whole grains, legumes, nuts, and olive oil 1, 2

Specific dietary restrictions 1:

• Limit excess fructose consumption and avoid processed foods with added sugars
• Replace saturated fats with polyunsaturated and monounsaturated fats
• Avoid processed foods, fast food, and commercial bakery goods

Exercise Prescription

• 150-300 minutes of moderate-intensity exercise (3-6 metabolic equivalents) OR 75-150 minutes of vigorous-intensity exercise per week 2
• Both aerobic and resistance training effectively reduce liver fat 1, 4
• Vigorous exercise provides greater benefit than moderate exercise for NASH and fibrosis 1
• Any increase in physical activity over previous levels is beneficial compared to continued inactivity 1

Pharmacological Treatment: Fibrosis Stage ≥F2 Only

For Non-Diabetic Patients

Vitamin E 800 IU daily is recommended for biopsy-confirmed NASH with significant fibrosis 1, 2, 4:

• Improves liver histology through antioxidant properties 1, 4
• Caution: Potential concerns about increased risk of all-cause mortality, hemorrhagic stroke, and prostate cancer with long-term use 1

For Diabetic Patients

Pioglitazone 30 mg daily is first-line pharmacotherapy 1, 2, 4:

• Improves all histological features except fibrosis 1
• Effective for biopsy-proven NASH with or without diabetes 1, 4
• Side effects: Weight gain, bone fractures in women, and rarely congestive heart failure 1

GLP-1 receptor agonists (e.g., semaglutide) should be considered for diabetic NASH patients, particularly those with significant fibrosis 2, 4:

• Provides dual benefits for diabetes and NASH 2
• Evidence is still emerging but shows promise 1

Emerging Therapies

Resmetirom may be considered for non-cirrhotic NASH with significant fibrosis (stage ≥2) if locally approved, demonstrating histological effectiveness on steatohepatitis and fibrosis with acceptable safety profile 4

Management of Comorbidities

• Statins for dyslipidemia: Safe in NASH patients with beneficial pleiotropic properties 1, 2
• Hypertension: Manage according to standard guidelines 2
• Diabetes: Prioritize GLP-1RAs, SGLT2 inhibitors, and pioglitazone for dual benefits 2
• Discontinue hepatotoxic medications: Corticosteroids, amiodarone, methotrexate, tamoxifen, estrogens, tetracyclines, and valproic acid 1

Bariatric Surgery Consideration

Bariatric surgery may be considered for morbidly obese patients meeting other medical criteria 1, 4:

• Nearly 85% of obese patients with biopsy-proven NASH have histologic resolution at one year following bariatric surgery 1
• Important caveat: Data to support bariatric surgery as a specific treatment for NASH is still lacking 1

Critical Pitfall to Avoid

All currently recommended pharmacologic treatments for NASH require histologic diagnosis prior to initiation 1—do not start vitamin E or pioglitazone without biopsy confirmation of NASH and fibrosis staging.