Hepatocellular carcinoma (HCC) is estimated to account for 6% of all human cancers worldwide. It is more common in men. There are 500,000 cases reported annually with a higher incidence (80%) in Southeast Asia and sub-Sahara Africa. 1 The major risk factors include hepatitis B and C, alcohol, aflatoxins, and hemochromatosis. 1 There is an increased incidence of HCC in the United States. HCC may present as a single mass, a diffuse process, or a large mass with satellite nodules.

The treatment options include surgery, percutaneous therapy, and systemic chemotherapy. Surgery (transplant or resection) offers the best treatment option with a reported 5-year survival rate ranging between 35% and 51% for hepatic resection and between 58% and 75% for orthotopic liver transplantation. 2 However, more than 75% of patients are unresectable at the time of diagnosis. Factors that affect prognosis include vascular invasion, number of lesions, tumor size ( > 5 cm), and presence of cirrhosis. 3

The primary goal of imaging is lesion detection and characterization. Additional roles of imaging include tumor staging and surveillance. A complete preoperative evaluation is critical for the appropriate selection of patients with HCC for whom surgical treatment may be attempted. Sonography, CT, and MRI may play a role in the evaluation of patients with suspected HCC. Of these imaging modalities, CT is the most commonly used in the diagnosis, staging, and surveillance of HCC.

On unenhanced CT, HCC appears hypodense to liver. Postcontrast CT images are required for the detection and characterization of HCC. The postcontrast CT evaluation should be performed in at least three different stages of contrast enhancement. These three stages are: the early hepatic arterial phase (17-20 seconds after contrast administration), the late hepatic arterial phase (4055 seconds), and the portal venous phase (70-80 seconds) (Figure 1). The rate of injection is an important technical factor and should be at 4 to 8 cc per second.

Figure 1. CT evaluation of the normal liver during the early arterial (1a), late arterial (1b), and portal venous (1c) phases of enhancement. The hepatic artery is opacified during the early arterial phase of enhancement (arrow on 1a). The portal vein is opacified on the late arterial phase (arrow on 1b). The middle hepatic vein branch is opacified on the portal venous phase (arrow on 1c).

The recent implementation of multislice CT (MSCT) with 4- and 16-row detectors has permitted the acquisition of images of the liver with 1.25-mm slice thickness during a single breath-hold (10 to 12 seconds). These thinner images not only provide increased resolution and improved lesion detection4 but also have permitted the production of excellent multiplanar reconstruction (MPR) without the stair-step artifact of thicker slices.

Figure 2. CT evaluation of the liver during the early arterial (2a), late arterial (2b), and portal venous (2c) phases of enhancement. The mass in segment III (white arrow) demonstrates the classic pattern of enhancement for HCC.

The classical appearance of HCC is of a highly vascular mass that demonstrates enhancement during the earlier phases of contrast enhancement and demonstrates a lower attenuation relative to liver on the delayed phase of enhancement 5,6 (Figure 2). In a patient with a clinical suspicion of HCC, a liver mass with these enhancement characteristics is diagnostic of HCC.

Figure 3. CT evaluation of the liver during the early arterial (3a), late arterial (3b), and portal venous (3c) phases of enhancement. The segments VII and VIII demonstrate an infiltrative type of HCC (dashed arrow). In segments II and III there are multiple lesions (solid arrow) that demonstrate the more common pattern of enhancement similar to that of focal nodular hyperplasia.

HCC more commonly demonstrates early enhancement, becoming isointense to liver in delayed images (Figure 3). This pattern of enhancement is indistinguishable from benign masses such as focal nodular hyperplasia (FNH), and regenerative and dysplastic nodules. In these cases, delayed scans at 3 to 10 minutes following contrast administration demonstrating lower attenuation of HCC increase the confidence in lesion characterization. 5 The detection of capsular enhancement during the late and delayed phases of enhancement also supports the diagnosis of HCC (see Figure 4).

Figure 4. CT evaluation of the liver during the early arterial (4a), late arterial (4b), and portal venous (4c) phases of enhancement. The mass in segment VI of the liver (solid arrow) demonstrates the classical pattern of enhancement with enhancement of the capsule on the delayed portal venous phase of enhancement (dashed arrow).

There are additional, multiple patterns of enhancement of HCC that are thought to be related to the degree of carcinogenesis and differentiation of HCC. 7 This is thought to be related to the development of HCC in a dysplastic nodule and the resultant increase in arterial flow within the nodule with a reduction in portal flow accounting for the various patterns of enhancement.

The sensitivity of multiphasic CT in detecting HCC nodules larger than 2 cm has been reported as 93.6%. 8 This decreases to 61% in the evaluation of smaller lesions. 8


MSCT also provides information essential for staging, management stratification, and surgical planning of patients with HCC.

MSCT can detect lesion number, size, and location. Utilizing multiphasic enhanced CT, vascular invasion also can be assessed, though HCC more commonly involves the portal vein. The distinction of bland thrombus from tumor thrombus is not always possible, but enhancement of the thrombus during the earlier phases following contrast administration is highly suggestive of tumor thrombus (see Figure 5). In addition to vascular invasion, the CT evaluation may detect associated signs of cirrhosis such as a nodular liver, an enlarged left lobe, ascites, and varices that may affect treatment options.

Figure 5. CT evaluation of the liver during the late arterial (5a) and portal venous (5b) phases of enhancement. There is arterial enhancement of the central portion of the portal vein in keeping with tumor thrombus (solid white arrow). Note the cavernous transformation of the portal vein (dashed white arrow).

Similarly to vascular invasion, biliary invasion may also be detected. 9 The presences of large nodes in the hepatoduodenal ligament (N1) are nonspecific, especially in a patient with hepatitis and/or cirrhosis. 10 In addition to providing staging information, MSCT and MPR can detect vascular anatomical variants. 11 In a series of transplant candidates, CT provided adequate staging in 92% of patients. 8


MSCT is also useful in the surveillance of patients with HCC. Enhancement changes at the surgical margin or radiofrequency ablation site are suggestive of recurrent or residual disease. 12

A pitfall of faster imaging examinations with MSCT is the increased detection of hepatic abnormalities related to preferential arterial flow that do not represent tumor. This may be due to anatomical variants, vascular obstruction, and arterio-portal shunting.

The utilization of optimum imaging techniques that include multiphasic imaging will enhance the role of MSCT in the management of patients with HCC, resulting in increased sensitivity for detection and characterization, improved staging and therapeutic planning, and increased sensitivity for recurrence or residual disease in surveillance following therapy.

Janio Szklaruk, PhD, MD, is assistant professor of radiology, MD Anderson Cancer Center, University of Texas, Houston.

Paul M. Silverman, MD, is chief of abdominal imaging and professor of radiology, MD Anderson Cancer Center, University of Texas, Houston.


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