What is the treatment for Non-Alcoholic Fatty Liver Disease (NAFLD)?

Treatment for NAFLD

The cornerstone of NAFLD treatment is lifestyle modification targeting 7-10% weight loss through caloric restriction and increased physical activity, with pharmacotherapy reserved exclusively for biopsy-proven NASH with significant fibrosis. 1, 2

Primary Treatment: Lifestyle Modification for All NAFLD Patients

Weight Loss Targets

• Achieve 7-10% total body weight loss to improve steatosis, inflammation, and potentially fibrosis 1, 2
• Even 3-5% weight loss improves hepatic steatosis, though greater loss (up to 10%) is needed to improve necroinflammation 1
• Weight loss must be gradual at less than 0.5-1 kg per week—rapid weight loss can precipitate acute hepatic failure in patients with advanced disease 1, 3, 4

Dietary Interventions

• Implement a Mediterranean diet pattern emphasizing vegetables, fruits, whole grains, legumes, olive oil as principal fat, moderate fish consumption, and minimal red meat 1, 2
• Achieve caloric deficit through reduction of refined carbohydrates and processed foods 1
• Eliminate or minimize fructose-containing beverages and foods with added sugars, as high fructose intake is independently associated with NAFLD development 1, 2
• Replace saturated fats with monounsaturated and polyunsaturated fats, particularly omega-3 fatty acids 2

Physical Activity Requirements

• Prescribe vigorous-intensity exercise (≥6 METs) for at least 150 minutes per week—moderate-intensity exercise alone does not improve NASH severity or fibrosis 3
• Both aerobic exercise and resistance training effectively reduce liver fat and should be tailored to patient preferences for long-term adherence 1, 2
• Exercise provides benefits independent of weight loss by improving insulin sensitivity 2, 5

Alcohol Consumption

• Strongly recommend abstinence from alcohol in patients with NAFLD and cirrhosis 1
• Patients with pre-cirrhotic NAFLD should minimize or abstain from alcohol to reduce risk of disease progression 1
• Heavy alcohol consumption must be avoided in all NAFLD patients 1, 2

Pharmacological Treatment: Reserved for Biopsy-Proven NASH with Fibrosis

Critical principle: Patients without NASH or fibrosis should receive only lifestyle counseling and no pharmacotherapy for their liver condition, as they have excellent prognosis from a liver standpoint 1, 2

When to Consider Pharmacotherapy

• Drug therapy is indicated for progressive NASH with bridging fibrosis and cirrhosis 1
• Also consider for early-stage NASH with increased risk of fibrosis progression (age >50 years, diabetes, metabolic syndrome, elevated ALT) 1
• All current pharmacotherapy for NAFLD is off-label, as no drug has been approved by regulatory agencies specifically for NASH 1, 3, 2

Vitamin E

• Consider vitamin E 800 IU daily in patients with biopsy-confirmed NASH without diabetes or cirrhosis 1, 3, 2
• Vitamin E improved histological features in the PIVENS trial 1

Pioglitazone

• Consider pioglitazone 30 mg daily in patients with biopsy-confirmed NASH without cirrhosis, with or without diabetes 1, 3, 2
• Pioglitazone improved all histological features except fibrosis and achieved NASH resolution more often than placebo 1
• Side effects include weight gain, bone fractures in women, and rarely congestive heart failure 1
• Pioglitazone has the advantage of treating both diabetes and NASH simultaneously in appropriate candidates 3

Metformin

• Metformin has no significant effect on liver histology and is NOT recommended as specific treatment for liver disease in adults with NASH 1, 3
• Use metformin as first-line agent for diabetes management when liver and renal function permit (eGFR >45 mL/min/1.73 m²), but not for NAFLD treatment 3

Management of Metabolic Comorbidities

Cardiovascular Risk Management

• Offer statin treatment to patients at increased cardiovascular risk (T2DM and/or QRISK-3 >10%) in accordance with guidelines 1
• Statins should NOT be withheld from patients with NAFLD, including those with compensated cirrhosis—hepatotoxicity is very rare and benefits significantly outweigh risks 1, 2
• Manage hypertension according to standard guidelines 1

Diabetes Management

• In patients with NAFLD and type 2 diabetes, consider glucose-lowering agents that promote weight loss and reduce cardiovascular risk (e.g., GLP-1 agonists) 1
• Avoid aggressive glycemic targets (A1C <7%) in advanced liver disease due to elevated hypoglycemia risk from impaired gluconeogenesis 3

Bariatric Surgery

• Consider referral for bariatric surgery in NAFLD patients with obesity who meet eligibility criteria according to national recommendations 1
• Bariatric surgery is a valid option for obese patients with NAFLD/NASH when otherwise indicated 1

Monitoring and Follow-Up

Patients with Advanced Fibrosis or Cirrhosis

• Perform right upper quadrant ultrasound with or without serum AFP every 6 months for HCC surveillance 3, 2
• Lifelong HCC surveillance is required even after metabolic improvement 3
• Perform esophagogastroduodenoscopy (EGD) screening for esophageal varices in patients with known cirrhosis 3, 2
• Regular reassessment of alcohol consumption 1

Patients Managed in Secondary Care

• Management should be by multidisciplinary teams with expertise in clinical hepatology, diabetes management, cardiovascular risk factors, and lifestyle intervention 1
• Patients with cirrhosis or significant-advanced fibrosis should continue secondary care management 1

Patients Discharged to Primary Care

• Provide clear recommendations on triggers for re-referral back to secondary care liver services 1
• Provide written information about NAFLD and weight management 1

Critical Pitfalls to Avoid

• Never pursue rapid weight loss (>1 kg/week) in NAFLD patients with advanced disease—this can precipitate acute hepatic failure 3, 4
• Do not prescribe pharmacotherapy to patients without biopsy-proven NASH and fibrosis 1, 2
• Do not use metformin as specific treatment for NAFLD histology despite its metabolic benefits 1, 3
• Do not withhold statins from NAFLD patients due to unfounded concerns about hepatotoxicity 1, 2
• Recognize that no specific pharmacotherapy has regulatory approval for NAFLD—all current options are off-label 1, 3, 2

Special Consideration: Lean NAFLD

• In lean patients with NAFLD, target modest weight loss of 3-5% through lifestyle intervention including exercise, diet modification, and avoidance of fructose and sugar-sweetened drinks 1
• Almost half of non-obese individuals achieved NAFLD remission with 3-5% weight loss, compared to 7-10% needed in obese individuals 1