What is the treatment for an adult patient with non-alcoholic fatty liver disease (NAFLD)?

Treatment for Fatty Liver Disease

Lifestyle modification through diet and exercise targeting 7-10% total body weight loss is the only proven first-line treatment for fatty liver disease, with pharmacotherapy reserved exclusively for biopsy-proven NASH with significant fibrosis (≥F2). 1

Weight Loss Targets by Disease Severity

The magnitude of weight loss directly correlates with histologic improvement 2:

• 5% weight loss: Decreases hepatic steatosis in 65% of patients 1
• 7% weight loss: Achieves NASH resolution in 64% of patients 2, 1
• 10% weight loss: Results in fibrosis regression in 45% and stabilization in the remaining 55% 1

For normal-weight patients (BMI ≤25 kg/m² non-Asian or ≤23 kg/m² Asian), a lower threshold of 3-5% weight loss provides similar histologic benefits for steatosis and NASH resolution 2

Dietary Intervention

Follow the Mediterranean diet as the primary dietary approach—this reduces liver fat even without weight loss. 2, 1, 3

Specific Caloric Prescription

Target 1200-1500 kcal/day or reduce baseline intake by 500-1000 kcal/day 2, 3. Critical pitfall: Do not exceed 1 kg weight loss per week, as rapid weight loss can worsen liver disease or precipitate acute hepatic failure 1

Foods to Emphasize Daily

• Fresh vegetables and fruits 2, 3
• Unsweetened whole grains rich in fiber 2, 3
• Fish or white meat 2, 3
• Olive oil as primary fat source 2, 3
• Nuts, seeds, and legumes 2, 3
• Replace saturated fats with PUFAs (especially omega-3) and MUFAs 2

Foods to Strictly Limit or Eliminate

• Completely eliminate fructose-containing beverages and sugar-sweetened drinks 1, 3
• Red meat and processed meat 2, 3
• Simple sugars and ultra-processed foods 2, 3
• Commercial bakery goods and fast food 2

Important caveat: Fructose contained in whole fruits is not associated with NAFLD, so fruit consumption should not be restricted 2

Exercise Prescription

Prescribe 150-300 minutes of moderate-intensity OR 75-150 minutes of vigorous-intensity aerobic exercise per week. 2, 1, 3

• Moderate-intensity is defined as 3-6 metabolic equivalents 3
• Vigorous-intensity is defined as >6 metabolic equivalents 3
• Resistance training can complement aerobic exercise and has independent benefits on NAFLD 2, 3
• Exercise reduces hepatic fat even without significant weight loss by improving insulin sensitivity 2, 3

Alcohol Restriction

Restrict or eliminate alcohol consumption entirely. 2, 3 Even low alcohol intake (9-20 g daily) doubles the risk of adverse liver-related outcomes in NAFLD patients compared to lifetime abstainers 3. For NASH-cirrhosis patients, total abstinence is mandatory to reduce hepatocellular carcinoma risk 1

Pharmacotherapy (Only for Biopsy-Proven NASH with Significant Fibrosis ≥F2)

Do not prescribe pharmacotherapy for mild NAFLD without biopsy-proven NASH and significant fibrosis. 1 For patients with simple steatosis, lifestyle modification is the sole intervention 1

Vitamin E

• 800 IU daily for non-diabetic, non-cirrhotic patients with biopsy-confirmed NASH 1, 4
• Improved NASH histology in 43% vs 19% with placebo (P=0.001) 4
• Critical limitation: No benefit on fibrosis (the only variable associated with mortality), and may increase prostate cancer and all-cause mortality risk 2

Pioglitazone

• 30 mg daily improves all histological features except fibrosis 1
• Achieves NASH resolution more often than placebo 1

GLP-1 Receptor Agonists

• For patients with type 2 diabetes and NASH: liraglutide or semaglutide 1
• Demonstrated NASH resolution in 39% vs 9% with placebo 1
• Safe in NAFLD and should be used for approved indications (diabetes, obesity) as they improve cardiometabolic outcomes 4

Metformin

Do not use metformin as specific NAFLD treatment—it has weak effect on liver fat, no significant effect on liver histology, and scarce evidence for histological efficacy 2, 4

Management of Metabolic Comorbidities

Aggressively treat all components of metabolic syndrome—cardiovascular disease, not liver disease, is the primary cause of mortality in NAFLD patients without cirrhosis. 2, 1, 3

• Statins are safe and should be used to treat dyslipidemia despite liver disease—they reduce hepatocellular carcinoma risk by 37% and hepatic decompensation by 46% 1
• Consider GLP-1 receptor agonists or SGLT2 inhibitors for diabetes 3
• Optimize blood pressure control for hypertension 3
• Avoid sulfonylureas and insulin when possible as they may increase hepatocellular carcinoma risk 3

Medications to Discontinue

Stop medications that worsen steatosis: corticosteroids, amiodarone, methotrexate, tamoxifen, estrogens, tetracyclines, valproic acid 1

Bariatric Surgery

Consider bariatric surgery for patients with BMI ≥35 kg/m² who fail lifestyle modifications, though effectiveness and safety have not been established in cirrhosis 1

Monitoring Strategy

• Use non-invasive tests (NAFLD Fibrosis Score) to identify patients at risk for advanced fibrosis 1
• Reserve liver biopsy for patients requiring diagnostic, therapeutic, and prognostic guidance 1
• Monitor liver enzymes (ALT, AST) periodically 1
• For cirrhosis patients: right upper quadrant ultrasound every 6 months for HCC screening, EGD screening for varices, transplant referral when appropriate 1

Unproven Interventions

Do not routinely recommend low-carbohydrate/high-protein diets, meal replacement protocols, intermittent fasting, or vitamin supplementation—these have not been adequately studied with histologic NAFLD endpoints 2