Hepatocellular Carcinoma Initial Assessment

Last updated: 27 November 2025

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Clinical Presentation

Signs and Symptoms  

Localized hepatocellular carcinoma is usually asymptomatic for much of its natural history. Non-specific symptoms with more advanced hepatocellular carcinoma include jaundice, anorexia, weight loss, malaise and upper abdominal pain. Physical signs are hepatomegaly and ascites.

Diagnosis or Diagnostic Criteria

Diagnostic Criteria  

The diagnosis of hepatocellular carcinoma is established by fulfilling the criteria of the 2018 American Association for the Study of Liver Diseases (AASLD) guidelines based on the Liver Imaging Reporting and Data System (LI-RADS).  

The criteria for LI-RADS 5, which confirm the diagnosis of hepatocellular carcinoma, include the following:

  • ≥20 mm lesions: Arterial phase hyperenhancement (APHE) and ≥1 of the following:
    • Non-peripheral "washout"
    • Enhancing capsule
    • Threshold growth (increase in lesion's size by ≥50% in ≤6 months)
  • 10-19 mm lesions: APHE and non-peripheral "washout" enhancing capsule and threshold growth, or APHE and "washout" or APHE and threshold growth
  • Lesions must be nodules >1 cm in diameter with imaging studies findings typical of hepatocellular carcinoma (ie hypervascular in the arterial phase with hypodensity in the portal venous or delayed phase) on a 4-phase (unenhanced, arterial, portal venous and delayed phases) MDCT scan, or a 4-phase dynamic contrast-enhanced magnetic resonance imaging in a liver that has cirrhosis


Biological imaging with gadoxetic acid may be utilized for the diagnosis of hepatocellular carcinoma for suspicious lesions that do not fulfill the AASLD requirements for diagnosis by imaging. There is a high likelihood of having high-grade dysplastic nodules or well-differentiated hepatocellular carcinoma in lesions without arterial phase hyperenhancement, but with both venous phase hypoenhancement and hepatobiliary phase hypointensity by gadoxetic acid-enhanced magnetic resonance imaging. These lesions should be considered as "high-risk" lesions. In patients with risk factors for hepatocellular carcinoma such as chronic viral hepatitis, liver cirrhosis, etc, an alternative diagnostic criterion can be met if space-occupying lesions of the liver demonstrated by computed tomography scan (non-dynamic) or magnetic resonance imaging (non-dynamic) are present, together with either: Serum alpha fetoprotein level of ≥400 mcg/L or dense homogenous lipiodol retention shown after hepatic lipiodol angiography with follow-up post-lipiodol computed tomography scan. 

Screening

Screening Methods  

Ultrasonography and alpha fetoprotein (AFP) testing are used for screening patients at risk for hepatocellular carcinoma. Patients with positive alpha fetoprotein or nodules ≥10 mm in ultrasound should undergo additional tests/imaging to confirm the diagnosis of hepatocellular carcinoma.  

Serum Alpha Fetoprotein (AFP)



Hepatocellular Carcinoma_Initial AssesmentHepatocellular Carcinoma_Initial Assesment




Serum alpha fetoprotein is a commonly used tumor marker for hepatocellular carcinoma and a widely used method of screening. An alpha fetoprotein cut-off value of 100 ng/mL was associated with high specificity but low sensitivity. There is a normal level in up to 35% of patients with small hepatocellular carcinoma and can be non-specifically raised in patients with active hepatitis or active hepatocyte regeneration. Recent studies have shown that it lacks adequate sensitivity and specificity for effective surveillance and diagnosis thus this screening method can be optional.  

Ultrasonography  

Ultrasonography is the radiographic choice for surveillance. A screening test and not a test to confirm diagnosis. This has a sensitivity of 94% in detecting lesions and a specificity of >90%. The recommended screening interval is 6 months in patients who are at risk and with a negative ultrasound result. For patients with <10 mm nodules in ultrasound, a repeat ultrasound and an alpha fetoprotein testing in 3-6 months is recommended.  

Computed Tomography (CT)/Magnetic Resonance Imaging (MRI)  

Computed tomography/magnetic resonance imaging are alternative imaging studies if the ultrasound is unable to detect nodules or with poor visualization.