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Looking to the Future – Blood-based Biomarkers for Liver Cancer Surveillance

Alpha-fetoprotein (AFP) is a blood-based biomarker that’s used together with ultrasound to detect liver cancer, but it’s by no means a perfect test. Experts are hopeful that emerging, specific blood-based biomarkers will prove useful in liver cancer surveillance — potentially as stand-alone tests.

What are some of the barriers to ultrasound surveillance?

For patients, some of the problems with ultrasound-based liver cancer surveillance include access to a clinic with an ultrasound machine, travel times and costs, as well as the inconvenience of attending appointments (1, 2). For clinicians, there may be differences in how the ultrasound is reported between sonographers (inter-observer variability) (1, 2).

What are the advantages of specific blood-based biomarkers over ultrasound alone?

Blood-based biomarker surveillance only requires a simple blood test. The risk of liver cancer is assessed using clinical scores, removing the need for ultrasound altogether (1, 2). Biomarker based surveillance may make it easier for patients to participate in liver cancer surveillance (1).

So, what blood-based biomarkers are currently used for liver cancer surveillance?

AFP is a blood-based biomarker currently used in hepatocellular carcinoma (HCC) surveillance in Australia (1). AFP tests are subsidised through the Medicare Benefits Schedule (MBS) for detecting and monitoring hepatic tumours (3). However, AFP use has been limited by its low sensitivity and suboptimal specificity (3).

While AFP is not used as a stand-alone surveillance test, it can help improve the detection of early-stage HCC when used together with ultrasound (1, 2).

What emerging biomarkers may be used for surveillance in the future?

There are two biomarkers showing promise for HCC surveillance, both of which are highly specific for the diagnosis of HCC (1):

  • lens culinaris agglutinin-reactive fraction of AFP (alpha-fetoprotein L3 or AFP-L3); and
  • des-gamma-carboxy prothrombin (DCP) (1).

Levels of these biomarkers are assessed using a simple blood test. The results of this blood test are used along with patient information to assess the risk of HCC. Two methods have been developed to calculate a clinical score, these are called GALAD and GAAD (1).

Both of these scores are still undergoing evaluation to check they have sufficient sensitivity and specificity (2). They are yet to be incorporated into clinical guidelines, or be subsidised by the MBS (3). If validated, the future use of non-invasive biomarkers for liver cancer surveillance holds promise, as it may allow for point-of-care testing with objective results (2).

GALAD

A serum biomarker-based model called GALAD can be used to predict the probability of HCC
in people with chronic liver disease (cirrhosis or chronic hepatitis B) (3).

The GALAD score is made up of (3):

G – gender (sex)
A – age
L – alpha-fetoprotein L3 (AFP-L3)
A – AFP
D – DCP

GAAD

Another clinical score using biomarkers is the GAAD score.

The GAAD clinical score is made up of (1):

G – gender (sex)
A – age
A – AFP
D – DCP

Further information

For a more in-depth discussion of blood-based biomarkers in HCC surveillance, see the Research Review Educational Series: Hepatocellular carcinoma surveillance and the emerging role of biomarker-based models (2023).

References:

  1. Hui S, Bell S, Le S, Dev A. Hepatocellular carcinoma surveillance in Australia: current and future perspectives. Med J Aust. 2023;219(9):432-8.
  2. Parikh ND, Tayob N, Singal AG. Blood-based biomarkers for hepatocellular carcinoma screening: Approaching the end of the ultrasound era? J Hepatol. 2023;78(1):207-16.
  3. Cancer Council Australia Hepatocelluar Carcinoma Surveillance Working Group. Clinical practice guidelines for hepatocellular carcinoma surveillance for people at high risk in Australia Sydney: Cancer Council Australia [updated April 2023. Available from:https://www.cancer.org.au/clinical-guidelines/liver-cancer/hepatocellular-carcinoma.

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