What is the management of fatty liver disease?

Management of Fatty Liver Disease

All patients with fatty liver disease require lifestyle modification targeting 7-10% weight loss through caloric restriction (500-1000 kcal/day deficit) and regular physical activity (150-300 minutes weekly of moderate-intensity exercise), which improves liver histology, reduces inflammation, and can reverse fibrosis. 1, 2

Initial Risk Stratification

Begin by calculating the FIB-4 score to determine treatment intensity and monitoring frequency 2, 3:

• FIB-4 <1.3 (Low Risk): Focus exclusively on lifestyle modifications with annual monitoring 2
• FIB-4 1.3-2.67 (Intermediate Risk): Obtain liver stiffness measurement by transient elastography 2, 3
  • LSM <8.0 kPa: Confirms low risk, annual monitoring
  • LSM 8.0-12.0 kPa: Aggressive lifestyle intervention, consider pharmacotherapy, monitor every 6 months 2
  • LSM >12.0 kPa: Indicates clinically significant fibrosis requiring multidisciplinary management 2, 4
• FIB-4 >2.67 (High Risk): Indicates high risk for advanced fibrosis, mandates hepatology referral 4, 3

Weight Loss Protocol

Target 7-10% total body weight reduction through a calorie deficit of 500-1000 kcal/day to achieve gradual weight loss of 500-1000g per week. 1, 2, 4

The dose-response relationship is critical 1, 5:

• 3-5% weight loss: Improves steatosis 1
• 5-7% weight loss: Decreases intrahepatic fat content and inflammation 1, 2
• >10% weight loss: Improves liver fibrosis in 45% of patients 1, 2

Critical caveat: Avoid rapid weight loss exceeding 1 kg/week, as this can worsen portal inflammation and fibrosis in some patients and may lead to acute hepatic failure after bariatric surgery. 1, 4

Dietary Intervention

Adopt a Mediterranean diet pattern as the primary dietary approach, which reduces liver fat even without weight loss. 1, 2, 5, 6

Specific daily recommendations 1, 2, 4:

• Consume: Vegetables, fruits, whole grains, legumes, nuts, fish, and olive oil as primary fat source
• Strictly limit: Simple sugars, fructose-containing beverages, red meat, processed meats, and ultra-processed foods

For caloric targets 1:

• Men: 1,500-1,800 kcal/day
• Women: 1,200-1,500 kcal/day
• Adjust based on age, sex, weight, and physical activity level

The Mediterranean diet emphasizes 40% calories from carbohydrates (versus 50-60% in typical low-fat diets) and 40% from fats (versus up to 30% in low-fat diets), with increased monounsaturated and omega-3 fatty acids. 1, 5

Low-carbohydrate diets are more effective than low-fat diets in reducing liver fat content and liver enzymes. 1

Physical Activity Prescription

Target a minimum of 150-300 minutes of moderate-intensity aerobic exercise weekly, or 75-150 minutes of vigorous-intensity exercise weekly. 1, 2, 4

The intensity matters 1:

• Vigorous exercise (≥6 METs): Associated with lower frequency of NASH and advanced fibrosis, provides full benefit including improvement in fibrosis 1
• Moderate exercise (3-6 METs): Improves steatosis and NASH severity but may not improve fibrosis 1

Examples of vigorous activities (>6 METs): Running, fast cycling, competitive sports 1

Examples of moderate activities (3-6 METs): Brisk walking, slow cycling, recreational swimming, dancing 1

Add resistance training as a complement to aerobic exercise, particularly beneficial for patients with poor cardiorespiratory fitness. 2, 4

Exercise reduces insulin resistance and liver fat content regardless of body weight changes. 1

Pharmacological Management

Pharmacotherapy should be reserved for patients with biopsy-proven NASH and fibrosis (stage F2 or higher), or those at high risk of disease progression (age >50 years, diabetes, metabolic syndrome, elevated ALT). 1

For Dyslipidemia

Use statins, which are safe in fatty liver disease and associated with a 37% reduction in hepatocellular carcinoma risk and 46% reduction in hepatic decompensation. 2, 4, 3

For Diabetes

Use GLP-1 receptor agonists as first-line glucose-lowering agents, which improve steatosis and may reverse steatohepatitis. 2, 4, 3

• Liraglutide achieved 39% NASH resolution versus 9% placebo 3
• Semaglutide achieved 59% NASH resolution versus 17% placebo 4

Consider pioglitazone (15-45 mg daily) for patients with biopsy-proven NASH, particularly those with type 2 diabetes. 1

• Improved all histological features except fibrosis in the PIVENS trial 1
• Side effects include weight gain, bone fractures in women, and rarely congestive heart failure 1

For Non-Diabetic NASH

Vitamin E (800 IU/day) can be considered for biopsy-proven NASH without diabetes or cirrhosis, though results are mixed in diabetic patients. 3

Hepatocellular Carcinoma Surveillance

Perform abdominal ultrasound every 6 months for HCC screening in patients with advanced fibrosis (F3) or cirrhosis. 2, 4, 3

Consider CT or MRI in overweight/obese patients where ultrasound quality is limited. 4

Patients with cirrhosis (thrombocytopenia or liver stiffness ≥20 kPa) require esophageal varices screening. 4

Monitoring Schedule

• Low-risk patients (FIB-4 <1.3, LSM <8.0 kPa): Annual monitoring with repeated FIB-4 and liver stiffness measurement 2, 3
• Intermediate/high-risk patients (FIB-4 >1.3, LSM >8.0 kPa): Monitor every 6 months with liver function tests and non-invasive fibrosis markers 2, 4, 3

Management of Comorbidities

All patients require aggressive management of metabolic comorbidities including obesity, hyperlipidemia, insulin resistance, and type 2 diabetes, as cardiovascular disease drives mortality before cirrhosis develops. 1, 4

Perform baseline cardiovascular assessment including lipid profile, HbA1c, blood pressure, and BMI. 4

Total abstinence from alcohol is mandatory in NASH-cirrhosis to reduce HCC risk. 1