From the Guidelines
Alpha-fetoprotein (AFP) is a valuable but imperfect biomarker for hepatocellular carcinoma (HCC) screening, diagnosis, and monitoring treatment response, with elevated levels above 400 ng/mL being highly suggestive of HCC, though sensitivity varies between 40-65% 1.
Key Points
- AFP is most useful when combined with imaging studies like ultrasound, CT, or MRI for HCC surveillance, as it can provide additional detection in 6-8% of cases not previously visualized by US 1.
- Not all HCC cases produce AFP, with approximately 30-40% of tumors being AFP-negative, and serial measurements are more informative than single values, as rising levels may indicate tumor progression or recurrence after treatment 1.
- AFP levels can also help assess treatment effectiveness, with declining values suggesting successful therapy, and have prognostic value, as very high levels (>10,000 ng/mL) often correlate with larger tumor size, vascular invasion, and poorer outcomes 1.
- However, AFP elevation can occur in other conditions like chronic hepatitis, cirrhosis, and certain germ cell tumors, so results must be interpreted in clinical context, and the use of AFP as a screening test has limitations due to its low sensitivity and specificity in early-stage HCC 1.
Clinical Recommendations
- For optimal HCC surveillance, AFP testing is typically recommended every 6 months in high-risk patients, especially those with cirrhosis, but the combination of AFP and ultrasound may not be recommended by some guidelines due to the increase in false positive results and costs 1.
- The use of AFP in combination with other tumor markers, such as des-gamma-carboxy prothrombin (DGCP), may enhance detection rates, but further studies are needed to confirm their roles in HCC surveillance 1.
- Ultrasound remains the preferred imaging modality for HCC surveillance due to its high sensitivity and specificity, but operator dependence and difficulty in scanning obese subjects are limitations 1.
From the Research
Value of Alpha-Fetoprotein in HCC
- The value of alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) is a widely used surveillance test for HCC among patients with cirrhosis 2.
- Studies have shown that AFP has a high sensitivity and specificity for the diagnosis of HCC, with a optimal cutoff value of 10.9 ng/mL leading to a sensitivity of 66% 2.
- The area under the receiver operating characteristic curve (AUROC) for AFP was 0.80, indicating its usefulness as a diagnostic marker for HCC 2.
- Other studies have also shown that AFP is a significant marker for HCC, helpful in assessing problems in management of HCC and monitoring treatment regimens 3.
- The threshold of AFP for the diagnosis of HCC is controversial, but a systematic review and meta-analysis found that an AFP threshold of 400 ng/mL had the highest area under the curve (AUC) of the summary receiver operating characteristic (SROC) and Q index, indicating its optimal threshold for HCC diagnosis 4.
Determinants of Alpha-Fetoprotein Levels
- Several factors have been identified as determinants of AFP levels in patients with HCC, including sex, presence of cirrhosis, liver disease with viral etiology, elevated alanine aminotransferase level, low albumin level, HCC tumor size, and presence of vascular invasion 5.
- These factors can influence serum AFP levels and should be taken into account when interpreting the oncologic meaning of this biomarker in clinical practice 5.