Screening for Hepatocellular Carcinoma

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To determine the role of screening and to screen in a cost-effective manner, it is important to define the high-risk patient population that is most likely to benefit from screening and to identify a readily available diagnostic modality that is sensitive, specific, and inexpensive. Moreover, to have a major effect on the outcome of hepatocellular carcinoma, the test should be applicable in the majority of high-risk subjects. Herein, we identify the high-risk patient population, discuss various diagnostic modalities, and recommend a practical and cost-effective strategy for screening.

Section snippets

HIGH-RISK POPULATION

Cirrhosis is the single most important risk factor for HCC throughout the world (3, 4, 5, 6, 7). HBV is the most common risk factor for the development of HCC worldwide (8, 9). Results of prospective and case-controlled studies have shown that HBV carriers are more likely to develop HCC than is the general population, and a universal vaccination for HBV has been shown to decrease the incidence of HCC in children (8, 9, 10, 11, 12). HBV-related HCC is seen predominantly (70%–90%) in patients

α-fetoprotein Level

α-fetoprotein (AFP) is the most commonly used tumor marker for screening. AFP is part of a super-gene family that encodes for many other proteins, including albumin and vitamin D binding protein, and is situated on chromosome 4 (4q11– q13). AFP is synthesized by the yolk sac during early fetal life and by the fetal liver during later fetal life. AFP levels decline rapidly after birth, and elevated levels are seen only in pathologic conditions. The cellular aspects of AFP reexpression in HCC

RADIOLOGIC IMAGING OF HCC

HCC is most commonly seen in patients with advanced cirrhosis, and the real challenge is to diagnose the tumor when it is very small (<2 cm). The commonly used imaging modalities are US, CT, and magnetic resonance (MR) imaging. The use of these modalities will be discussed only briefly in this section because it will be covered in more detail elsewhere. A wide range of sensitivities, specificities, positive predictive values, and negative predictive have been reported in the literature for

US

US is the most widely used imaging modality for screening high-risk patients. Small HCCs (<3 cm) are hypoechoic at US, and larger tumors have an infiltrative mosaic with a complex echogenicity pattern. The presence of a pseudocapsule is highly suggestive of an HCC. The sensitivity of US in the detection of HCC ranges from 35% to 84%, and more objective studies have reported a lower sensitivity of 35%– 59% (57, 58). US is very much operator dependent, and this may explain the conflicting reports

CT

On CT scans, the attenuation of most HCC foci is lower than that of the surrounding liver tissue. Small, welldifferentiated tumors, however, may not have low attenuation, and this may pose a diagnostic dilemma. The use of dynamic helical CT has substantially improved the diagnostic accuracy by enabling imaging of the liver in the arterial, portal venous, and equilibrium phases (69, 70, 71, 72). The portal and equilibrium phases have proved to be very useful in the detection of differentiated,

SCREENING PROTOCOLS

The natural history of HCC is variable. It has been estimated that the doubling time of tumor size may range from 1 to 19 months, with a median of 4–6 months. This is the rationale for screening at 6-month intervals, but many investigators have suggested that, because of the unpredictable tumor growth rate, screening be done more frequently (3-month intervals) in a high-risk population (4, 58). Patients with smaller tumors (<2 cm) have a substantially better prognosis. In a large study (74),

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    Neither author has identified a conflict of interest.

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