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Case Study: The Problems with AFP Testing

for Health Care Providers

4: The problems with AFP testing: A case of AFP level rising to 800 µg/L, with no detectable mass

Background

A 74-year-old man has a history of compensated hepatitis C cirrhosis. He has been screened regularly for HCC by his provider for more than 3 years. AFP levels have been tracked regularly as well, and they have been elevated and slowly increasing from approximately 400 µg/L to the current count of 834 µg/L. However, repeated screening over time, including magnetic resonance imaging (MRI), dynamic computed tomography (CT), and ultrasound, has not identified any discrete lesion.

Discussion

Questions

  • Who should be screened for HCC?
  • How useful is tracking the AFP level in HCC screening?
  • When should tracking the AFP level be considered helpful?

Speaker 1: Regarding HCC, the population at risk is really any patient with cirrhosis. But those patients with hepatitis B and C have the highest risk. Statistics show that hepatitis B carriers develop HCC with incidence of 0.5% per year, but for patients with chronic hepatitis B and cirrhosis, the risk is 2.5% per year. With chronic hepatitis B, it is not the case that cirrhosis must be present in order to have a risk of developing HCC. Though we often aren't looking for it, HCC can arise in an essentially normal appearing liver, and if one is not looking for HCC, it can affect the interpretation of the imaging. In chronic hepatitis C with cirrhosis, the risk of HCC is 2-8% per year. We like to think that Stage I and Stage II fibrosis in hepatitis C are not associated with liver cancer, but I believe we all have seen cases in which the patient does not have cirrhosis and yet HCC has arisen in the liver.

Speaker 2: If the patient is coinfected with HIV and HCV, the risk of developing liver cancer is the same as for patients with HCV alone. However, the progression of HCC in a coinfected patient is much more rapid. This may be true in other immunosuppressed states as well, such as recurrent HCC when immunosuppressed after liver transplant.

Speaker 1: When we talk about these screening tests, the first--and probably historically, the one that has been around the longest--is AFP measurement. It was previously thought that the sensitivity of the AFP test was 90%, but now we know it is only about 60%. That means 40% of patients with liver cancer, sometimes extensive liver cancer, will have a normal AFP level, and therefore measuring AFP by itself is not thought to be a very good screening test because of this poor sensitivity. I suspect you knew that, but I think we all order AFP tests anyway. Not everyone believes these tests to be completely reliable, but if there is a change in the AFP level, or if it is more than 100 µg/L or more than 600 µg/L, the sensitivity improves.

Speaker 2: Abdominal ultrasound in some centers has a good sensitivity for detecting HCC, as high as 65-80%, but the procedure is very operator dependent. I noticed in my own institution that one means of improving the sensitivity was to tell the ultrasound technicians to look only at the liver. Even if you request "HCC screening," they will scan the kidneys and the pancreas and whatever else that they can find. But if you specify "liver only," they spend a lot of time scanning the liver. But I must admit that I have never discovered an HCC by ultrasound imaging. Even when I have a CT scan that shows significant disease, the ultrasound has really not been helpful.

I want to emphasize that conventional CT scanning will yield only 2 contrasts--an early venous contrast and a late venous contrast. However, HCC is a hypervascular tumor with increased hepatic arterial supply. Classically, the tumor has hepatic arterial enhancement, and during the portal venous and equilibrium phases, the tumor fades off. Therefore, it is very important to use a multiphase or triple-phase CT scan to identify any lesion that enhances in the arterial phase.

Some point out that MRI is more sensitive but less specific than CT scanning--better able to detect small lesions but less accurate in distinguishing HCC from dysplastic nodules. In general, MRI is much less available than CT, but the availability of MRI varies from institution to institution. At my VA medical center, we have an extremely good CT radiology group, and we have to send patients to the university facility for MRI tests, so we rely exclusively on CT scanning. Other VA facilities rely exclusively on MRI, and even the radiologists debate which technique is better for HCC detection. Both CT and MRI have low sensitivity (approximately 50%) for small lesions less than 2 cm in diameter and even lower sensitivity (approximately 30%) for lesions less than 1 cm in diameter. I feel that, if there are questions regarding the results of one modality, using the other to confirm the findings can be beneficial.

Speaker 1: So what should be done if a lesion is found? The easy recommendation is that large, hypervascular lesions of more than 2 cm in diameter, when seen on two separate imaging modalities, such as CT and MRI, are more than 95% likely to be cancerous, and therapeutic modalities are appropriate. A biopsy is not necessary in such cases. With small lesions that are less than 1 cm in diameter, it is OK to just monitor them. Our CT radiologist would say there is no point in scanning small lesions more frequently than every 6 months because you are looking for HCC in the background of cirrhosis. There are thousands of very small hepatic nodules with abnormal vasculature, and if a little bit of contrast becomes caught in one of those nodules, it will look like an HCC. Lesions smaller than 1 cm in diameter often go away before a subsequent CT scan is performed, but if they become larger, one can begin to look for HCC. And lesions of that size--between 1 and 2 cm in diameter--are the most controversial in terms of treatment recommendations. The Avon, Somerset, and Wiltshire (ASW) Cancer Services guidelines recommend performing biopsies on such lesions. I have a very hard time persuading interventional radiologists to perform biopsies on the small lesions because, although a positive result will instill confidence in your diagnosis, a negative result will give rise to doubt about the reliability of the finding.

Summary Points

  1. HCC screening is recommended because patients with hepatitis C cirrhosis have a 2-8% per year risk of acquiring HCC. It should be noted that HCC can arise from hepatitis C before the development of cirrhosis, but that occurrence is much less common.
  2. AFP tests have a low sensitivity and specificity at values less than 100 µg/L. As the AFP level rises, the sensitivity and specificity of the tests increase. Imaging alone is a better approach to screening for HCC than AFP testing alone.
  3. Ultrasound can be an excellent screening modality, but it is operator or facility dependent, and technicians must focus on looking for hepatic masses.
  4. CT scanning is an excellent modality if done with contrast in the arterial and venous phases, which allows detection of the early arterial enhancement and venous washout that are the vascular dynamics of an HCC lesion. Specifically, either a multiphase or triple-phase CT scan of the abdomen to rule out HCC is the preferred test.
  5. MRI is also an excellent modality, but it is not always available and it usually is not necessary prior to a triple-phase CT scan, unless CT is not available or is contraindicated.
  6. If CT scanning identifies a lesion 2 cm in diameter or larger, MRI may be helpful to confirm the diagnosis without a biopsy.

Facilitators/Speakers

  • Ann Busch, Liver Transplant Clinical Nurse Specialist, Portland VAMC
  • Sue Currie, Associate Director, HCRC, San Francisco VAMC
  • Guadalupe Garcia-Tsao, Director, HCRC, Connecticut VAMC
  • Douglas Heuman, Liver Transplant Program Director, Richmond VAMC
  • Alexander Monto, Director, HCRC, San Francisco VAMC
  • Roberta Ruimy, Manager, Liver/Kidney Transplant Programs, Portland VAMC
  • Brenda Salvas, Health System Specialist, Manager, Liver and Kidney Transplant Program, VA Transplant Program, VA Central Office, Washington, DC
  • Anna Sasaki, Staff Physician, Portland VAMC
  • Kristine Stick, Nurse Practitioner for Hepatology, San Francisco VAMC
  • Suchat Wongcharatrawee, Associate Director HCRC, Connecticut VAMC

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