What is the first‑line treatment for an adult with non‑alcoholic fatty liver disease who presents with intermittent chest pain, neutrophilic leukocytosis, blurred vision and associated metabolic risk factors?

First-Line Treatment for Non-Alcoholic Fatty Liver Disease

Lifestyle modification targeting 7–10% total body weight loss through combined dietary change and structured exercise is the only proven first-line treatment for all adults with NAFLD, regardless of metabolic comorbidities or presenting symptoms. 1, 2, 3

Immediate Management Priorities

Address Metabolic Comorbidities Aggressively

• Cardiovascular disease, not liver disease, is the leading cause of mortality in NAFLD patients without cirrhosis—the chest pain warrants urgent cardiovascular evaluation and aggressive risk-factor control. 2, 3
• Statins must not be withheld due to liver disease; they are safe in NAFLD, reduce hepatocellular carcinoma risk by 37%, and reduce hepatic decompensation by 46%. 2, 3
• The neutrophilic leukocytosis requires investigation for concurrent infection or inflammatory process unrelated to NAFLD itself. 1
• Blurred vision in the context of metabolic syndrome suggests uncontrolled diabetes or hypertensive retinopathy—check HbA1c, fasting glucose, and arrange ophthalmology referral. 2, 4

Weight-Loss Strategy (Core Therapy)

Target and Expected Outcomes

• ≥7% body weight loss achieves NASH resolution in ~64% of patients. 2, 3
• ≥10% body weight loss produces fibrosis regression in ~45% and stabilization in the remaining 55%. 2, 3
• Weight loss must be gradual (≤1 kg/week); rapid loss >1.6 kg/week can precipitate acute hepatic decompensation or worsen fibrosis. 3

Dietary Prescription

• Adopt a Mediterranean dietary pattern (high in vegetables, fruits, whole grains, legumes, olive oil, fish; low in red meat and processed foods)—this reduces liver fat even without weight loss. 1, 2, 3
• Create a daily caloric deficit of 500–1000 kcal (approximately 1500–1800 kcal/day for men; 1200–1500 kcal/day for women). 3, 4
• Eliminate all fructose-containing beverages and sugar-sweetened drinks. 1, 3
• Replace saturated fats with monounsaturated and omega-3 polyunsaturated fatty acids. 3, 4

Exercise Prescription

• Vigorous-intensity aerobic exercise (≥6 METs, e.g., running, cycling >16 km/h) is required to improve NASH severity and fibrosis; moderate-intensity activity alone does not alter histology. 3
• Prescribe 75–150 minutes per week of vigorous-intensity aerobic exercise or 150–300 minutes per week of moderate-intensity exercise. 1, 2, 3
• Include resistance training to augment metabolic benefits and preserve lean body mass. 3, 4

Management of Metabolic Risk Factors

Diabetes and Insulin Resistance

• If the patient has type 2 diabetes, prioritize GLP-1 receptor agonists (liraglutide, semaglutide)—they achieve NASH resolution in 39–59% versus 9–17% with placebo, promote weight loss, and reduce cardiovascular events. 2, 3
• SGLT-2 inhibitors are recommended for diabetes management and provide additional weight-loss benefits. 2
• Metformin should not be used as NAFLD-specific therapy; it has minimal hepatic efficacy but may be continued for diabetes management. 3

Dyslipidemia

• Statins are safe and strongly recommended for all patients with dyslipidemia; they confer hepatoprotective effects and reduce liver-related complications. 2, 3, 4

Hypertension

• Treat hypertension according to standard guidelines; angiotensin receptor blockers may have additional hepatic benefits but are not specifically indicated for NAFLD. 1

Alcohol Consumption

• Restrict or eliminate alcohol consumption—even modest intake accelerates disease progression. 1
• In pre-cirrhotic NAFLD, limit to ≤1 drink/day for women and ≤2 drinks/day for men; in NASH-cirrhosis, total abstinence is mandatory. 3

Risk Stratification and Monitoring

Initial Fibrosis Assessment

• Calculate FIB-4 score as the initial screening tool: FIB-4 <1.3 indicates low risk; 1.3–2.67 intermediate risk; >2.67 high risk of advanced fibrosis. 4
• Patients with intermediate or high FIB-4 should undergo transient elastography (liver stiffness <8.0 kPa = low risk; 8.0–12.0 kPa = intermediate; >12.0 kPa = high risk). 4
• Refer patients with high-risk scores to hepatology for consideration of liver biopsy and specialized management. 2, 4

Ongoing Surveillance

• Annual follow-up with repeated FIB-4 calculation to monitor for fibrosis progression in low-risk patients. 4
• More frequent monitoring (every 6 months) with liver function tests and non-invasive fibrosis markers in intermediate- and high-risk patients. 4

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

Pharmacologic therapy is not indicated for simple steatosis or mild NAFLD without biopsy-proven steatohepatitis and significant fibrosis. 2, 3

If Biopsy Confirms NASH with ≥F2 Fibrosis

• Vitamin E 800 IU daily is the most established therapy for non-diabetic, non-cirrhotic patients with biopsy-proven NASH. 2, 3
• Pioglitazone 30 mg daily improves all histologic features except fibrosis and yields higher NASH-resolution rates than placebo; it can be used in diabetic or non-diabetic patients. 2, 3
• Resmetirom may be considered for non-cirrhotic NASH with significant fibrosis, as it demonstrated histological effectiveness on steatohepatitis and fibrosis with acceptable safety. 4

Critical Pitfalls to Avoid

• Do not prescribe pharmacotherapy without biopsy-proven NASH and significant fibrosis (≥F2)—lifestyle modification alone is appropriate for simple steatosis. 2, 3
• Do not withhold statins due to unfounded hepatotoxicity concerns; they are safe and beneficial in NAFLD. 2, 3
• Do not pursue rapid weight loss exceeding 1 kg/week—this can worsen liver disease or precipitate acute hepatic failure. 3
• Do not rely on liver-enzyme normalization alone as a treatment endpoint; histological improvement is required to prevent progression. 2
• Discontinue medications that aggravate steatosis: corticosteroids, amiodarone, methotrexate, tamoxifen, estrogens, tetracyclines, valproic acid. 3

Bariatric Surgery Consideration

• For patients with BMI ≥35 kg/m² who fail lifestyle interventions, bariatric surgery achieves histologic NASH resolution in ~85% at one year post-procedure. 3
• Surgery is contraindicated or lacks established safety in cirrhosis or very high BMI with advanced fibrosis. 3