When should non-alcoholic fatty liver disease (NAFLD) with hepatic steatosis that hasn't resolved with dietary measures be referred to a hepatologist or for medical management?

From the Guidelines

Patients with hepatic steatosis that hasn’t resolved with dietary measures should be referred to a hepatologist when there are signs of advanced liver disease, persistently elevated liver enzymes, evidence of fibrosis, or presence of risk factors like diabetes or obesity with poor control, as indicated by the latest guidelines 1. When considering referral, several key factors come into play, including the presence of cardiometabolic risk factors, abnormal liver enzymes, and radiological signs of hepatic steatosis, particularly in individuals with type 2 diabetes or obesity with additional metabolic risk factors 1.

Key Considerations for Referral

• Presence of advanced liver disease
• Persistently elevated liver enzymes (ALT/AST >2 times normal for over 6 months)
• Evidence of fibrosis on imaging or non-invasive testing
• Presence of risk factors like diabetes or obesity with poor control
• Symptoms like persistent right upper quadrant pain or fatigue

Medical Management

Medical management becomes necessary when simple steatosis progresses to non-alcoholic steatohepatitis (NASH) or when fibrosis is detected. The current approach focuses on managing underlying conditions with lifestyle modifications, including weight loss, dietary changes, physical exercise, and discouraging alcohol consumption, as well as optimal management of comorbidities 1.

Treatment Options

• Lifestyle modification
• Optimal management of comorbidities, including use of incretin-based therapies (e.g., semaglutide, tirzepatide) for type 2 diabetes or obesity, if indicated
• Bariatric surgery as an option in individuals with MASLD and obesity
• Consideration for MASH-targeted treatment with resmetirom in adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2), if locally approved and dependent on the label 1

Importance of Referral

Referral to a hepatologist is crucial because progression to advanced fibrosis increases mortality risk. Hepatologists can provide comprehensive evaluation, including specialized testing like FibroScan or liver biopsy when needed, and may offer clinical trial opportunities for emerging therapies targeting fatty liver disease 1.

From the Research

Hepatic Steatosis Referral Criteria

When hepatic steatosis hasn't resolved with dietary measures, referral to a hepatologist or for medical management is crucial. The following points highlight the key considerations:

• Hepatic steatosis is a significant pathological feature of chronic liver disease, characterized by ongoing inflammation and fibrosis 2.
• The presence of hepatic steatosis can lead to liver metabolic dysfunction, inflammation, and advanced forms of nonalcoholic fatty liver disease 3.
• Persistent severe hepatic steatosis is independently associated with fibrosis progression, and routine assessment of liver fat content is essential for risk assessment in patients with chronic hepatitis B 4.
• Secondary causes of steatohepatitis, such as rare hereditary liver and metabolic diseases, intestinal diseases, endocrine disorders, and drugs, should be considered during the diagnostic workup, and treatment of the underlying disease should be started to halt disease progression 5.
• Hepatic steatosis and fibrosis are associated with cardiorespiratory fitness impairment, and these relations are partly mediated by pathways of altered lipid metabolism and general cardiometabolic risk 6.

Key Considerations for Referral

The following factors should be considered when deciding to refer a patient with hepatic steatosis that hasn't resolved with dietary measures:

• Presence of fibrosis or severe steatosis
• Association with other liver diseases, such as chronic hepatitis B
• Presence of secondary causes of steatohepatitis
• Impairment of cardiorespiratory fitness
• Altered lipid metabolism and cardiometabolic risk factors

Referral Timing

Referral to a hepatologist or for medical management should be considered when:

• Dietary measures have failed to resolve hepatic steatosis
• There is evidence of fibrosis progression or severe steatosis
• Secondary causes of steatohepatitis are suspected or identified
• Cardiorespiratory fitness is impaired, and metabolic mediators are altered 6