What is the next step for a patient with untreated Hepatitis C Virus (HCV) and elevated Alpha-Fetoprotein (AFP), an ultrasound or advanced imaging?

Management of Elevated AFP in Untreated HCV Patient

Ultrasound is the appropriate next step for a patient with untreated HCV and mildly elevated AFP of 12 ng/mL, rather than advanced imaging. 1

Rationale for Ultrasound as First-Line Imaging

• Ultrasound combined with AFP is the recommended surveillance strategy for HCC in patients with chronic liver disease, including those with untreated HCV 1
• For patients with elevated AFP but no previously detected liver lesions, ultrasound serves as the initial imaging modality before proceeding to more advanced techniques 1
• Ultrasound has a specificity greater than 90% when used as a screening test for HCC, making it appropriate as the first imaging study 1
• The combination of ultrasound with AFP has been shown to increase detection rates of HCC compared to either test alone, with pooled sensitivities of 63% for early-stage HCC 1

Interpretation of AFP Level of 12 ng/mL

• An AFP level of 12 ng/mL is mildly elevated but below the typical cutoff of 20 ng/mL used in most clinical settings 1
• AFP elevations in HCV patients without HCC are common and may be related to:
  • Degree of liver inflammation and fibrosis 2, 3
  • Viral replication and hepatocyte turnover 4
  • Gender and racial factors, with higher levels seen in females and Black patients 2
• In HCV patients, AFP may be elevated due to the underlying liver disease rather than HCC, with prevalence of elevated AFP (≥10 ng/mL) in approximately 11-12% of chronic HCV patients without HCC 3

Diagnostic Algorithm

1. Initial step: Perform abdominal ultrasound as the first imaging study 1

   • If ultrasound is normal: Continue surveillance with ultrasound and AFP every 6 months 1
   • If ultrasound shows lesion(s) <1 cm: Follow up with repeat ultrasound in 3 months 1, 5

2. For lesions 1-2 cm detected on ultrasound:

   • Proceed with at least two dynamic studies (triphasic CT, contrast-enhanced MRI, or contrast-enhanced ultrasound) 1, 5
   • If both show characteristic HCC features: Diagnose as HCC 1
   • If findings are inconclusive: Consider biopsy or short-term follow-up imaging 1

3. For lesions >2 cm detected on ultrasound with typical HCC features:

   • Proceed directly to triphasic CT or MRI for confirmation 1, 5
   • Lesions >2 cm with typical features on dynamic imaging can be diagnosed as HCC without biopsy 5

Important Clinical Considerations

• Ultrasound performance may be suboptimal in obese patients or those with very nodular cirrhotic livers, with sensitivity for early HCC detection of only 47% 1
• In cases where ultrasound is technically limited (severe obesity, hepatic steatosis), consider proceeding directly to cross-sectional imaging 1
• While MRI has superior sensitivity for small HCC detection compared to ultrasound (90% vs 50%), it is not cost-effective as a first-line screening tool for all patients 1
• For HCV patients with bridging fibrosis (F3) or cirrhosis (F4), continued HCC surveillance is recommended even after achieving sustained virologic response 1

AFP Interpretation in HCV Context

• The specificity of AFP for HCC increases with higher cutoff values, but sensitivity decreases 1, 6
• At a cutoff of 20 ng/mL, AFP has sensitivity of 60% and specificity of 84% for HCC detection 6
• In HCV patients specifically, some studies suggest using a higher cutoff of 59 ng/mL may be more appropriate 1
• Persistently elevated AFP over time is more concerning than a single elevated value 4

Advanced imaging should be reserved for cases where ultrasound detects a suspicious lesion or when ultrasound quality is inadequate due to technical limitations 1, 5.