Screening modalities and intervals

See also liver cancer surveillance and cirrhosis.

Screening for HCC in at-risk patients is expensive and time consuming, and only relatively recently has it been shown to lead to improved patient outcomes. Nonetheless, it is considered standard practice within the gastroenterology and hepatology community in developed areas of the world. Screening is generally performed using both serum alpha-fetoprotein (AFP) and hepatic imaging by ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI), at intervals of every 6 months. No screening strategy is perfect: patients have been found at transplant to have tumors that were not seen on imaging, or to have no tumor in areas that were suspicious by imaging.

No randomized controlled trial of screening or surveillance in patients at risk for HCC, with disease-specific or all-cause mortality as end points, has been published, and none is expected, as serial liver imaging with measurement of serum AFP in cirrhotic patients is now considered standard practice. Studies that reflect improved outcomes with these strategies are being published. An Italian group found that patients undergoing screening and aggressive therapy for HCC diagnosed after 1997 had smaller tumors and improved yearly mortality compared with patients diagnosed during earlier periods.

Serum testing for AFP

Between 50% and 85% of hepatocellular carcinomas produce AFP, which normally is not present at high levels in the blood of adults. Elevation of AFP is fairly sensitive for the detection of HCC. In one study of patients with chronic HCV, the sensitivity and specificity of an AFP greater than 20 ng/mL for the diagnosis of HCC were 67% and 89%, respectively. Pregnancy, germ cell tumors, and chronic inflammatory liver diseases can also elevate AFP levels. The positive predictive value of an AFP greater than 20 ng/mL is poor, since minor elevations are common in patients with chronic liver disease. In one prospective study of 200 patients with chronic HCV infection, 13% of those without cirrhosis and 47% of those with cirrhosis had a serum AFP level greater than 10 ng/mL. When studied in patients with HCV-related cirrhosis specifically, an AFP greater than 200 ng/mL in the setting of a hepatic mass was found to be essentially diagnostic of HCC, although lower levels were not as specific. African Americans with HCC also tended to have less AFP elevation than Caucasians with HCC, making AFP a less helpful marker in them.

Ultrasonography

Ultrasound is the standard imaging modality for HCC screening, and a skilled operator can often visualize tumors that are 1 cm or greater in diameter. Ultrasound sensitivity for detection of such tumors across several studies is in the range of 60%, with specificity of around 90%. The cirrhotic liver can make visualization of small HCCs very difficult, so screening practices should be individualized based on the resources available at each location where screening is performed.

Other imaging studies

Other radiological techniques, including CT and MRI, are even more sensitive than ultrasound in detecting small lesions in the liver. One study found the sensitivity of HCC detection to be 79.4% for ultrasound, 81.6% for CT, and 88.9% for MRI. The cost effectiveness of these imaging studies compared with ultrasound remains to be demonstrated, however, as unrelated liver abnormalities that require evaluation are detected by the increasingly sensitive techniques.

References

References for this page are listed on the Background and Epidemiology page.