What are the diagnostic tests for hepatocellular carcinoma (HCC)?

From the Guidelines

Screening for hepatocellular carcinoma (HCC) is recommended for high-risk individuals, primarily using ultrasound examination of the liver every 6 months, often combined with alpha-fetoprotein (AFP) blood testing, as stated in the most recent guidelines 1. High-risk groups include patients with cirrhosis from any cause, chronic hepatitis B carriers, and those with a family history of HCC. If abnormalities are detected during screening, further diagnostic tests are typically ordered, including:

• Contrast-enhanced CT scans
• MRI with liver-specific contrast agents These imaging studies can confirm the diagnosis based on characteristic enhancement patterns without requiring a biopsy in many cases. For indeterminate lesions, a liver biopsy may be necessary. Early detection through regular screening significantly improves survival rates by identifying tumors when they are small and more amenable to curative treatments such as surgical resection, liver transplantation, or ablation therapies. The biological basis for using AFP as a marker relates to its production by liver cancer cells, though it's not specific to HCC and can be elevated in other conditions, which is why imaging is essential in the diagnostic process 1.

Some key points to consider in the diagnosis of HCC include:

• The use of multiphasic contrast-enhanced CT or MRI as first-line imaging studies 1
• The importance of imaging diagnosis in high-risk patients, with a liver nodule ≥1 cm detected by surveillance test can be diagnosed as an HCC if it shows radiological hallmarks of HCC 1
• The role of AFP in the diagnosis of HCC, with an AFP greater than 200 ng/mL having a very high positive predictive value for HCC in cirrhotic patients with a mass in the liver 1
• The limitations of AFP as a screening test, with a low positive predictive value in populations with a low prevalence of HCC 1

Overall, the diagnosis of HCC requires a combination of clinical, laboratory, imaging, and pathology examinations, with a focus on early detection and characterization of liver nodules in high-risk individuals 1.

From the Research

Diagnostic Tests for Hepatocellular Cancer

• The diagnosis of hepatocellular carcinoma (HCC) can be made using various tests, including abdominal ultrasound (US), alpha-fetoprotein (AFP) measurement, and imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) 2, 3, 4.
• A study published in 2021 found that the combination of AFP and US had the highest sensitivity for diagnosing HCC, with a sensitivity of 96% and specificity of 85% 2.
• The same study found that using AFP with a cut-off of 20 ng/mL had a sensitivity of 60% and specificity of 84%, while US alone had a sensitivity of 72% and specificity of 94% 2.
• Another study published in 2022 discussed the limitations of AFP as a tumor marker for HCC, including its low sensitivity and specificity, and the variability in its accuracy depending on patient characteristics and AFP cut-off values 5.
• A systematic review and meta-analysis published in 2020 found that the optimal threshold for AFP in diagnosing HCC was 400 ng/mL, which had a higher sensitivity and specificity compared to lower thresholds 6.
• The American Association for the Study of Liver Diseases (AASLD) guidelines recommend the use of the Barcelona Clinic Liver Cancer (BCLC) staging system, which combines imaging and clinical predictors of survival to determine stage and treatment options 3.
• A systematic review published in 2006 found that US, CT, and MRI had varying degrees of sensitivity and specificity in diagnosing HCC, with MRI being the most sensitive and US being highly specific but insufficiently sensitive 4.

Imaging Modalities

• CT and MRI are commonly used imaging modalities for diagnosing HCC, with CT being more widely available and MRI being more sensitive 3, 4.
• A study published in 2006 found that the pooled estimates of CT studies had a sensitivity of 68% and specificity of 93%, while MRI studies had a sensitivity of 81% and specificity of 85% 4.
• The AASLD guidelines recommend the use of multiphasic CT or MRI to assess focal liver lesions identified at ultrasonographic surveillance in patients with cirrhosis 3.

Biomarkers

• AFP is a commonly used biomarker for HCC, but its accuracy is limited by its low sensitivity and specificity 2, 5, 6.
• A study published in 2022 discussed the potential of novel biomarkers such as AFP-L3, Golgi specific membrane protein (GP73), and des-gamma-carboxyprothrombin to improve the accuracy of HCC diagnosis 5.
• The combination of AFP with these novel biomarkers may improve the diagnostic accuracy of HCC, but further studies are needed to confirm this 5.