What is the recommended treatment for non‑alcoholic fatty liver disease (NAFLD) in patients of all ages?

Treatment of Fatty Liver Disease (NAFLD) Across All Ages

Lifestyle modification targeting 7-10% weight loss through caloric restriction and increased physical activity is the first-line treatment for all patients with NAFLD, regardless of age, with no currently approved pharmacological therapy for routine use. 1, 2

Core Treatment Strategy for All Ages

Weight Loss Targets and Methods

The cornerstone of NAFLD treatment is achieving specific weight loss thresholds that correlate with histologic improvement:

• 5% weight loss reduces hepatic steatosis 1
• 7% weight loss achieves NASH resolution 1
• 10% weight loss results in fibrosis regression or stability 1

Critical caveat: Weight loss must be gradual at 500-1000g per week maximum—rapid weight loss (>1kg/week) can precipitate acute hepatic failure and worsen liver disease. 2, 3

Dietary Interventions

Implement a Mediterranean diet pattern as the primary dietary approach, which reduces liver fat even without weight loss: 1, 2

• Daily vegetables, fruits, fiber-rich whole grains, legumes, nuts, and olive oil as principal fat source 2
• Moderate fish or white meat consumption with minimal red meat 2
• Eliminate commercially produced fructose-containing beverages and processed foods 1, 2
• Replace saturated fats with monounsaturated and polyunsaturated fats, especially omega-3 fatty acids 2

Caloric restriction targets: Create a 500-1000 kcal/day deficit, typically achieving 1200-1500 kcal/day total intake 1, 2

Exercise Requirements

Prescribe 150-300 minutes of moderate-intensity aerobic exercise per week OR 75-150 minutes of vigorous-intensity exercise: 1, 2

• Vigorous-intensity exercise (≥6 METs) provides greater benefit than moderate exercise for NASH severity and fibrosis 3
• Resistance training complements aerobic exercise and has independent beneficial effects on NAFLD 1
• Exercise alone, even without weight loss, reduces hepatic fat by improving insulin sensitivity 2

Age-Specific Considerations

Children and Adolescents

For overweight or obese children and adolescents with NAFLD, lifestyle correction is the sole recommended treatment—no pharmacological therapy is currently recommended: 1

Specific lifestyle modifications include:

• Restrict simple sugar-added beverages 1
• Increase moderate physical activity 1
• Reduce screen time to less than 2 hours per day 1
• Improve dietary habits focusing on whole foods 1

Bariatric surgery consideration: Only for severe obesity (BMI ≥40 or ≥35 with major obesity-related complications) when skeletal growth is nearly complete (Tanner stage 4 or higher: 13-14 years for girls, 15-16 years for boys) and after lifestyle modifications and medical management have failed. 1

Important note: Vitamin E showed histological improvement in the TONIC trial for ages 8-17 years, but long-term high-dose vitamin E is not recommended due to safety concerns. 1 Other agents (ursodeoxycholic acid, docosahexaenoic acid, fish oil) showed no significant benefit. 1

Adults

For adults, the treatment algorithm is stratified by fibrosis risk:

Low Fibrosis Risk (FIB-4 <1.3 for age <65 or <2.0 for age ≥65)

• Manage in primary care with lifestyle modifications alone 1
• Focus on gradual weight loss through calorie reduction and increased physical activity 1
• Monitor periodically with non-invasive fibrosis markers 2

Indeterminate or High Fibrosis Risk

• Continue aggressive lifestyle modifications 2
• Consider second-line testing with enhanced liver fibrosis (ELF) score for indeterminate FIB-4 (1.3-3.25) 1
• Refer to hepatology for advanced fibrosis assessment 1

Pharmacological Considerations (Off-Label, Limited to Specific Populations)

No pharmacotherapy has been approved by regulatory agencies specifically for NAFLD treatment—all current options are off-label: 2, 3

Pharmacological treatment should be limited to patients with biopsy-proven NASH and significant fibrosis: 2, 3

• Vitamin E (800 IU daily): Consider in biopsy-confirmed NASH without diabetes or cirrhosis 3
• Pioglitazone (30 mg daily): Consider in biopsy-confirmed NASH without cirrhosis, with or without diabetes 3

Management of metabolic comorbidities is essential:

• Statins are safe and recommended for dyslipidemia in NAFLD patients, including those with compensated cirrhosis—they reduce HCC risk by 37% 2, 4
• GLP-1 agonists can be effective for NASH recovery in diabetic patients 4
• Metformin is NOT recommended as specific treatment for NAFLD histology, though it can be used for diabetes management when liver and renal function permit 3

Alcohol Restriction

Alcohol consumption should be restricted or eliminated from the diets of all adults with NAFLD, particularly those with pre-cirrhotic NAFLD or cirrhosis, as alcohol accelerates disease progression. 1, 2

Monitoring and Comorbidity Management

Aggressively manage all metabolic comorbidities, as cardiovascular disease is the main driver of morbidity and mortality in NAFLD patients before cirrhosis develops: 2, 4

• Assess and treat diabetes, hypertension, dyslipidemia, and cardiovascular disease 1, 2
• Use non-invasive fibrosis scores (FIB-4, NAFLD Fibrosis Score) to identify patients at risk for advanced fibrosis 1, 2
• For patients with cirrhosis: perform HCC screening with ultrasound ±AFP every 6 months and EGD screening for varices 2, 3

Bariatric Surgery for Adults

Consider bariatric surgery referral for NAFLD patients with obesity who meet national eligibility criteria—it resolves NASH in 85% of patients at 1 year and improves steatosis, steatohepatitis, and fibrosis. 2, 4

Critical Pitfalls to Avoid

• Never pursue rapid weight loss—this can precipitate acute hepatic failure in patients with advanced disease 2, 3
• Do not withhold statins due to unfounded hepatotoxicity concerns—benefits significantly outweigh minimal risks 2
• Sustainability is key—choose dietary and exercise regimens that patients can maintain long-term 2
• Avoid sodium restriction below 60 mmol/day in patients with ascites 3