Improved Surveillance Is Urgently Needed to Help Reduce the Burden of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is all too common—and often deadly. Despite a deep understanding of its risk factors and recent advances in treatment, the prognosis for patients who have late-stage HCC is grim.

Hepatocellular Carcinoma in the United States

Hepatocellular carcinoma accounts for nearly all cases of liver cancer. A recent report on the status of cancer in the United States shows that from 2012 to 2016, liver cancer had the greatest annual percentage change in incidence among the 17 most common cancers:

In addition, the incidence of liver cancer is projected to more than double over the next 2 decades to 100,000 cases in 2040, and the annual number of deaths is expected to rise simultaneously to 41,000.

Prevention Is Crucial

Owing to the increasing prevalence of HCC and its poor prognosis, and in particular because the risk factors for HCC are well known, the prevention and early detection of HCC should be urgently undertaken.

Prevention and risk reduction

The absolute prevention of HCC is a formidable challenge; however, because we know much about the risk factors for developing chronic liver disease, cirrhosis, and HCC, risk reduction is possible.

In the United States, the incidence of HCC is higher among men than women, and it is higher among American Indians and Alaskan Natives, Hispanics, and Pacific Islanders than among non-Hispanic blacks and non-Hispanic whites. Sex, race, and ethnicity aside, many risk factors that may lead to HCC are modifiable.

It is possible to reduce the impact of chronic viral hepatitis due to hepatitis B virus and hepatitis C virus with vaccination against hepatitis B virus and viral load-decreasing treatments for both infections. However, HCC associated with alcohol use remains high in the United States even though its risk may be modified. Hepatocellular carcinoma risk factors such as obesity and nonalcoholic fatty liver disease (NAFLD) are also modifiable.

Potentially curative treatment options are available to patients when HCC is detected in its early stages. Unfortunately, HCC is often detected too late, leaving patients and their loved ones with little hope of long-term survival.

Early Detection of HCC Improves Patient Outcomes

Routine, biannual surveillance can detect HCC early when curative treatments remain available, leading to improved patient outcomes. However, current surveillance methods (ultrasonography with or without alpha-fetoprotein measurement [AFP]) may be inadequate owing to limitations in performance, access, and adherence.

Limitations of HCC surveillance methods: performance, access, and adherence

Three important limitations of conventional surveillance methods require attention. The first is inadequate performance. The sensitivity of ultrasonography in combination with a blood test to measure AFP is only 63% sensitive in detecting HCC early in patients. When ultrasound imaging is employed without AFP, the sensitivity of early-stage detection drops to 47%.

Moreover, the accuracy of ultrasound imaging for the detection of HCC is decreased further still among patients who are obese and those patients who have NAFLD or nonalcoholic steatohepatitis. Consequently, HCC may not be detected early enough in these growing populations to allow patients to undergo potentially curative treatment.

The second limitation is inadequate access. Approximately 3 million Americans qualify for guideline-recommended surveillance, but only one third receive it. Access is particularly problematic for many patients who are followed up in primary care. In this setting, primary care physicians may have concerns and misconceptions that limit the success of surveillance, including the notion that physical examinations and the monitoring of liver enzymes are sufficient to detect HCC.

Third and no less important than performance and access is adherence. Half of all patients for whom surveillance is recommended report that scheduling ultrasonography appointments, out-of-pocket costs, and transportation challenges decrease adherence to routine surveillance.

Adherence can be challenging, too, when patients fail to fully appreciate the seriousness of the disease risks that they face. In this context, physicians may face their own challenges: Providing education and encouragement to their patients to keep up with routine surveillance is difficult during busy office-visit encounters. Each patient’s comorbidities may also raise important competing clinical concerns that take precedence over conversations about surveillance.

A new approach to HCC surveillance

A new approach to reducing the burden of HCC is urgently needed. Key components of this approach must include convenient access, interventions that improve adherence, and most important, improved performance of HCC detection methods.

Progress towards these goals has been made. For instance, Chalasani and colleagues recently reported the development and clinical validation of a novel, high-performance multitarget HCC blood test that is now available as the Oncoguard^® Liver test.

At 87% specificity, the test demonstrated detection of HCC with

• 82% early-stage sensitivity
• 88% overall sensitivity

The performance of the test, when compared with current blood-based surveillance recommendations, was shown to be more sensitive in the detection of early-stage HCC than AFP.

The Oncoguard^® Liver test represents a comprehensive approach to the routine surveillance of HCC. The test is simple, requiring one blood draw at a single location. The Oncoguard^® Liver test is now part of a streamlined solution that includes physician support, patient education, and mailed outreach.