What is the management approach for diffuse steatotic liver (fatty liver disease)?

Management of Diffuse Steatotic Liver (Fatty Liver Disease)

The cornerstone of management for diffuse steatotic liver disease (now termed metabolic dysfunction-associated steatotic liver disease or MASLD) is lifestyle modification, including weight loss of 7-10%, Mediterranean diet pattern, and regular physical activity of at least 150 minutes per week of moderate intensity exercise. 1, 2

Diagnostic Approach

• Case-finding strategies using non-invasive tests should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis 1
• A stepwise approach using blood-based scores (such as FIB-4) followed by imaging techniques (such as transient elastography) is recommended to assess for advanced fibrosis 1
• Liver biopsy is not suited for routine monitoring due to its invasiveness but may be used in individual cases to assess disease progression or treatment response 1

Non-Pharmacological Management

Weight Loss

• In adults with MASLD and overweight/obesity, dietary and behavioral therapy should aim for sustained weight reduction of: 1, 2

  • 5% to reduce liver fat

  • 7-10% to improve liver inflammation

  • 10% to improve fibrosis

Dietary Modifications

• Mediterranean dietary pattern is strongly recommended, characterized by: 1, 2
  • Limited consumption of ultra-processed foods rich in sugars and saturated fats
  • Avoidance of sugar-sweetened beverages
  • Increased intake of fruits, vegetables, whole grains, legumes, nuts, and olive oil 2

Physical Activity

• Physical activity should be tailored to individual preference and ability, with a target of: 1, 2

  • 150 minutes/week of moderate-intensity activity OR

  • 75 minutes/week of vigorous-intensity physical activity

Other Lifestyle Considerations

• Coffee consumption has been associated with improvements in liver damage and reduced liver-related clinical outcomes in observational studies 1
• Nutraceuticals cannot be recommended due to insufficient evidence of effectiveness and safety 1
• In normal-weight adults with MASLD, diet and exercise interventions should still be recommended to reduce liver fat 1

Pharmacological Management

• If approved locally and dependent on the label, adults with non-cirrhotic MASH (metabolic dysfunction-associated steatohepatitis) with significant liver fibrosis (stage ≥2) should be considered for treatment with resmetirom 1, 2
• Resmetirom has demonstrated histological efficacy on steatohepatitis and fibrosis in a large phase III trial with an acceptable safety profile 1
• No MASH-targeted pharmacotherapy is currently recommended for patients at the cirrhotic stage 1
• For patients with comorbid type 2 diabetes or obesity, incretin-based therapies (e.g., semaglutide, tirzepatide) should be considered as they may have beneficial effects on MASLD 1, 2, 3

Special Considerations

• Bariatric surgery is an option for individuals with MASLD and obesity who don't respond to lifestyle interventions 1, 2
• A multidisciplinary approach is strongly recommended given the connections between MASLD and cardiometabolic comorbidities 1, 2
• Management of MASH-related cirrhosis includes nutritional counseling, surveillance for portal hypertension and hepatocellular carcinoma, and consideration of liver transplantation in decompensated cirrhosis 1

Monitoring

• Non-invasive tests may be repeatedly used to assess fibrosis progression in a tailored fashion but provide limited information about treatment response 1
• Regular follow-up is necessary to assess liver function, fibrosis progression, and treatment response 2, 4
• Hepatocellular carcinoma surveillance is indicated for patients with MASH-related cirrhosis 2, 5