Surveillance for Hepatocellular Carcinoma in Patients With Cirrhosis

Ju Dong Yang; W. Ray Kim

Disclosures

Clin Gastroenterol Hepatol. 2012;10:16-21. 

In This Article

Management Strategies and Supporting Evidence

Who Are the Candidates for Hepatocellular Carcinoma Surveillance?

Hepatocellular carcinoma surveillance should be performed in a group of patients whose risk for HCC development is sufficiently high to make it cost-effective ( Table 2 ). Surveillance is considered effective if it increases life expectancy by more than 3 months and considered cost-effective if less than $50,000 is needed to increase 1 quality-adjusted life-year. Under this concept, the incidence of HCC is the primary determinant of the cost-effectiveness of surveillance.

The first category of candidates for surveillance is patients with cirrhosis. Cirrhosis is the single most important risk factor for HCC, and most patients with HCC have underlying liver cirrhosis. According to a guideline from AASLD, surveillance is recommended when the HCC incidence is higher than 1.5% in a patient with cirrhosis. This category of patients includes those with cirrhosis from viral hepatitis, nonalcoholic steatohepatitis, and primary biliary cirrhosis, and thus these patients should be under a surveillance program. In addition, experts recommend patients with other types of cirrhosis to receive surveillance, although firm data about the incidence of HCC in this group of patients are lacking.

In implementing surveillance, one of the common challenges is to identify patients with cirrhosis. Because viral hepatitis is easily recognizable, patients at risk for chronic viral hepatitis infection need to be screened for HBV and/or hepatitis C virus according to the established guidelines. It is also important to have a high index of suspicion of chronic liver disease in patients with abnormal liver function test, significant alcohol history, or metabolic syndrome.

The diagnosis of cirrhosis is straightforward in patients with hepatic decompensation, on the basis of the characteristic symptoms of portal hypertension and liver failure. Hepatocellular carcinoma surveillance in this group of patients would be most meaningful if liver transplantation is available. Under the current allocation system, an early-stage HCC within the socalled Milan criteria increases the priority of receiving a liver transplant from a deceased donor. In contrast, if liver transplantation is not available, surveillance in patients with hepatic decompensation severe enough to disallow meaningful therapy is unlikely to be beneficial.

Diagnosing patients with compensated liver cirrhosis might present a challenge because patients are usually asymptomatic without an overt sign of portal hypertension. Although histology is considered the gold standard for the diagnosis of cirrhosis, a liver biopsy is invasive and subject to sampling variability. Various laboratory data and mathematical models have been proposed to noninvasively identify patients with cirrhosis. Transient elastographic techniques with magnetic resonance imaging (MRI) or US measure the stiffness of the liver, which correlates with hepatic fibrosis. As data accumulate in support of accuracy of these techniques in identifying asymptomatic cirrhotic patients, they are gaining wider acceptance in clinical practice.

The other category of candidates for surveillance is HBV carriers who might develop HCC without cirrhosis. In those subjects, surveillance is warranted when the HCC incidence is higher than 0.2%/year. These high-risk hepatitis B carriers include Asian men older than 40 years and Asian women older than 50 years. Although the annual incidence of HCC in individuals of African race or those with family history of HCC cannot be firmly established, they are also recommended to undergo surveillance starting at an earlier age ( Table 2 ).

What Modality is to be Used for Surveillance?

Most guidelines advocate abdominal US as the standard surveillance test for HCC. It has sensitivity greater than 60% and specificity greater than 90% as a screening test for HCC. It is widely available and less expensive than CT or MRI. It does not expose patients with repeated radiation. However, there are several weaknesses of US as a surveillance test for HCC. Abdominal US is highly dependent on the operator. Because small HCC often presents with a nonspecific appearance, detecting an early HCC nodule can be challenging, particularly in a patient with a nodular cirrhotic liver. Sensitivity of US is further decreased in obese subjects. Because of the high prevalence of obesity in the United States, the utility of US as an HCC surveillance test in those patients has been questioned.

These limitations of US have prompted some clinicians to use abdominal CT or MRI in select patient groups, eg, those waiting for liver transplantation. However, the risk of repeated radiation and contrast exposure and high cost are obvious limitations that prevent its routine use in the broader population at risk. Finally, serum AFP is commonly used as an adjunct to abdominal US, although its use as a surveillance test for HCC remains controversial.

What is the Next Step if a Suspicious Lesion is Found by a Surveillance Test? (Recall Policy)

Once a suspicious lesion is found on US, a systematic algorithm, also known as the recall policy, can be followed to appropriately and expeditiously diagnose an HCC (Figure 1). If the nodule is smaller than 1 cm, a close follow-up with a repeat US at 3 months is recommended. If the lesion is found to enlarge to a size larger than 1 cm, a dynamic imaging study (CT or MRI) should be performed. If the size of the lesion remains the same for more than 2 years, the original 6-month follow-up might be resumed.

Figure 1.

Lesions on surveillance US: recall policy.

For lesions that appear larger than 1 cm on US, a contrastenhanced dynamic CT or MRI must be performed. If characteristic vascular features (arterial enhancement and venous washout) are seen, a diagnosis of HCC is established. If the imaging characteristics are not typical, a second dynamic scan should be performed (if the first modality was CT, then MRI, and vice versa). If it shows the characteristic vascular features, a diagnosis of HCC might be made. If not, a percutaneous biopsy of the lesion should be considered, although the biopsy might not always be diagnostic. Finally, if there is considerable increase in serum AFP in the absence of a demonstrable lesion on US, a contrast-enhanced dynamic CT or MRI should be performed.

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