How is liver stiffness measurement (LSM) used for hepatocellular carcinoma (HCC) risk stratification in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)?

Liver Stiffness Measurement for HCC Risk Stratification in MASLD

Liver stiffness measurement (LSM) should be used in combination with clinical variables and risk scores to stratify HCC risk in patients with MASLD, with LSM ≥15 kPa in patients with elevated FIB-4 indicating high risk requiring HCC surveillance. 1

Risk Stratification Framework for HCC Surveillance in MASLD

Step 1: Initial Risk Assessment with FIB-4

• Use FIB-4 as first-line test with age-specific cutoffs:
  • Age <65 years: FIB-4 <1.3 (low risk), 1.3-2.67 (intermediate), >2.67 (high risk)
  • Age ≥65 years: FIB-4 <2.0 (low risk), 2.0-2.67 (intermediate), >2.67 (high risk) 1, 2

Step 2: Refine Risk Assessment with LSM

• For patients with intermediate/high FIB-4:
  • LSM <8 kPa: Low risk for HCC
  • LSM 8-15 kPa: Intermediate risk
  • LSM ≥15 kPa: High risk (annual HCC incidence >1%) 1, 2

Step 3: HCC Surveillance Recommendations

• High-risk patients requiring surveillance:

  • FIB-4 ≥3.25 (annual HCC incidence 1.18%) 2
  • LSM ≥20 kPa as standalone test (annual HCC incidence >1%) 2
  • LSM ≥15 kPa in patients with elevated FIB-4 (annual HCC incidence >1%) 2
  • All patients with MASLD-related cirrhosis 1

• Intermediate-risk patients to consider for surveillance:

  • Non-cirrhotic MASLD with diabetes and LSM ≥10 kPa (annual HCC incidence 0.46%) 3
  • FIB-4 2.67-3.25 (annual HCC incidence 0.77%) 2
  • Patients with F3 fibrosis based on individual risk assessment 1

• Low-risk patients (surveillance not recommended):

  • Non-cirrhotic MASLD with fibrosis stage <F3 1
  • FIB-4 below age-specific low cutoffs with LSM <8 kPa 2

Additional Risk Factors to Consider

Several factors increase HCC risk in MASLD patients and should be considered when making surveillance decisions:

• Presence and duration of T2D and/or obesity 1
• Older age 1
• Concurrent alcohol intake and/or smoking 1
• Increasing LSM over time (≥19% increase) 4

Surveillance Protocol

• Imaging modality: Ultrasound every 6 months 1
• Additional testing: Alpha-fetoprotein (AFP) measurement can be combined with ultrasound, particularly in high-risk patients with obesity where ultrasound sensitivity is reduced 1
• Alternative imaging: Consider MRI in selected high-risk patients with poor ultrasound visualization, especially those with dysplastic or regenerative nodules 1

Practical Implementation Challenges

• Ultrasound-based surveillance has low sensitivity (45%) for early HCC detection in MASLD patients with obesity 1
• Inter-system variability should be considered when interpreting results from different elastography techniques, as values and cutoffs are not directly comparable 1
• Annual repeated LSM measurements can help refine risk stratification in patients with compensated advanced chronic liver disease (cACLD) 1

Clinical Pitfalls to Avoid

1. Don't rely solely on a single LSM value - changes in LSM over time provide additional prognostic information, with a ≥19% increase indicating higher risk for liver-related events, even in patients with initially low LSM 4

2. Don't overlook patients with F3 fibrosis - they have an intermediate risk of HCC that is lower than cirrhosis but not negligible 1

3. Don't miss MASLD-related cirrhosis - it is often under-recognized compared to other etiologies, with less than 25% of cirrhotic patients undergoing appropriate HCC surveillance 1

4. Don't ignore metabolic comorbidities - T2D and obesity significantly increase HCC risk and should factor into surveillance decisions 1, 3

The two-step approach using FIB-4 followed by LSM effectively identifies patients at different risks of liver-related events, supporting current guideline recommendations for non-invasive risk stratification in MASLD 5.