What is a commonly used marker for carcinoma (CA) of the liver?

Alpha-Fetoprotein (AFP) as a Marker for Hepatocellular Carcinoma

Alpha-fetoprotein (AFP) is the most commonly used tumor marker for hepatocellular carcinoma (HCC), though it has significant limitations in both sensitivity and specificity. 1, 2

Diagnostic Value of AFP for Liver Cancer

• AFP is traditionally and commonly used as a tumor marker for HCC, with normal range being 10-20 ng/ml, and levels >400 ng/ml typically considered diagnostic for HCC 3, 2
• AFP has poor sensitivity ranging from 39% to 65% for HCC diagnosis, with specificity ranging from 76% to 97% depending on the cut-off values used 1
• At the commonly used cut-off of 20 ng/ml, AFP shows good sensitivity but low specificity, while at higher cut-offs of 200 ng/ml, sensitivity drops significantly to only 22%, though specificity improves 3, 1
• Serum AFP level is normal in up to 35% of cases of small HCC and can be nonspecifically raised in patients with active hepatitis or active hepatocyte regeneration 3
• In a large study of 1,158 HCC patients, only 18% had AFP values >400 ng/ml, while 46% had completely normal AFP levels (<20 ng/ml) 2

Limitations of AFP as a Diagnostic Tool

• AFP is only elevated in 40-60% of HCC cases, particularly showing poor sensitivity in early-stage disease 1, 2
• Only a small portion of tumors at an early stage (10-20%) have abnormal AFP serum levels 3
• Fluctuating levels of AFP in patients with cirrhosis might reflect flares of HBV or HCV infection, exacerbation of underlying liver disease, or HCC development 3
• False positive AFP elevations can occur in active hepatitis, regenerating nodules in cirrhosis, pregnancy, and other cancers, such as intrahepatic cholangiocarcinoma, colon cancer metastases, lymphoma, and germ cell tumors 1, 2

Surveillance Recommendations

• Western guidelines (AASLD, EASL-EORTC, and ESMO-ESDO) recommend ultrasound (US)-based surveillance and do not recommend the combination with AFP 3
• The NCCN guideline states that AFP may have utility for enhancing detection of HCC when used in combination with US in the screening setting for at-risk individuals 3
• Most Asian guidelines recommend surveillance programs based on a combination of US and AFP 3
• The Japanese Society of Hepatology (JSH) guideline indicates the combined use of tumor markers (AFP >200 ng/mL, AFP-L3 >15%, or DCP >40 mAU/mL) for the diagnosis of HCC 3
• When combined with US, AFP levels can provide additional detection in only 6-8% of cases not previously visualized by US 3

Alternative and Complementary Markers

• Other biomarkers, including the lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-gamma-carboxy prothrombin (DCP), have been studied as potential markers for HCC 3
• Diagnostic models combining AFP with AFP-L3% and PIVKA-II (DCP) have shown improved efficacy in the diagnosis of liver cancers, with models like GALAD, ASAP, GALAD-C, and C-GALAD showing the highest efficacy 4
• A rising AFP over time, even if not reaching diagnostic levels (>400 ng/ml), is highly suspicious for HCC 2

Clinical Implications

• When AFP is normal but HCC is suspected based on risk factors or imaging, further imaging studies should be performed, and biopsy may be necessary for definitive diagnosis 2
• Imaging studies, including ultrasound, CT scanning, and MRI, are crucial for diagnosis when AFP is normal, and combining multiple imaging techniques improves diagnostic accuracy 3, 2
• For high-risk patients, such as those with cirrhosis or chronic hepatitis, the American College of Gastroenterology recommends surveillance with ultrasound examination every 6 months 2

In conclusion, while AFP remains the most widely used tumor marker for HCC, it should be interpreted cautiously due to its limitations in sensitivity and specificity. Combining AFP with imaging studies, particularly ultrasound, provides the most effective approach for HCC surveillance and diagnosis.