HCC: Evolving Screening and Surveillance

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One strategy for early identification and treatment of hepatocellular carcinoma (HCC) is to institute a screening and surveillance program for patients at high risk. Screening is defined as the first testing, and surveillance as regular testing, of at-risk patients. Key risks associated with the development of HCC, explains Robert G. Gish, MD, FAASLD, include hepatitis C, hepatitis B, alcoholic steatohepatitis (ASH), and nonalcoholic steatohepatitis (NASH). The emerging risk of NASH is changing screening and surveillance approaches to include patients with fatty liver disease. In patients who have cirrhosis, surveillance should be continued until that cirrhosis reverses, states Gish.

With the new presence of the protease inhibitors, notes Ghassan K. Abou-Alfa, MD, hepatitis C—related HCC can be expected to almost disappear. Beyond the protease inhibitors, Gish adds, there is combination therapy with polymerase inhibitors and S5A inhibitors. However, because there are still many people with hepatitis C and cirrhosis, Gish believes it will be another decade before a marked decline is seen. Still, today many patients with HCC also have hepatitis C, which can now be treated simultaneously, subsequently improving their liver function and their portal hypertension, and decreasing their risk of recurrent disease.

The obesity epidemic is contributing to the challenges of preventing, screening, diagnosing, and treating liver disease and liver cancer. Once a BMI is over 30 to 32, ultrasound quality starts to decline, explains Gish, and other methods must be employed, such as alternating ultrasound with MR or ultrasound with CT, or using biomarkers to decide when advanced imaging is needed.

Biomarkers are also being used in conjunction with imaging to decide when to stop surveillance. The most common measure is alpha-fetoprotein (AFP). In addition to AFP, Gish has used AFP-L3% and des-gamma-carboxy prothrombin for nearly a decade. Approximately 15% to 20% of patients with HCC have normal AFP levels, but, he explains, most these patients have at least 1 of these other 2 biomarkers. If you test for these biomarkers regularly, it may queue into the need for advanced imaging. These biomarkers, he stresses, are more appropriate for assessing the risk for cancer, than for the diagnosis of cancer.

Most surveillance programs still rely on ultrasound, states Jeff Geschwind, MD. Though ultrasound is the least expensive, he notes, it has the problem of being very operator-dependent, and findings are often subjective. In addition, there is an issue with sensitivity, particularly in patients who are obese or who have smaller tumors. According to Geschwind, the sensitivity of ultrasound decreases significantly when the tumor size is <1 cm. Guidelines are clear, he adds, about taking the next step in screening, including 4-phase CT or MRI, if any suspicious mass is found in a patient with cirrhosis.