Hepatocellular carcinoma has a high mortality rate—Improved surveillance may help reduce it

For more than 2 millennia, the liver has been considered to be critical to our health and wellbeing. In the second half of the 20th century, developments in technology led to important medical milestones such as the first human liver transplantation and the Nobel Prize–winning discovery of the cancer-causing hepatitis B virus.

New medical technology will no doubt continue to drive life-saving innovations in the management of liver cancer; these must include advances in early detection and treatment. To help achieve that end, it is critical to recognize liver cancer risks and identify those people who live with them, increase access and adherence to liver cancer surveillance, and substantially improve the tools used to conduct surveillance.

Mortality rates have doubled since 1980

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. It’s also the fastest growing cause of cancer-related deaths in the United States.

The American Cancer Society estimates that more than 40,000 new cases of HCC, occurring mostly in men, will be diagnosed in 2021. Owing to the high occurrence of HCC in men, more men will die than women: Of the more than 30,000 deaths expected in 2021, two thirds will occur in men. However, with the rise of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) and the obesity epidemic, this may change in the future.

Advanced HCC has poor outcomes and must be caught early

Late-stage HCC has limited treatment options. Consequently, the prognosis for patients with an initial diagnosis of advanced HCC is poor. Discovering HCC in its earliest stages opens the door to potentially curative treatment options. When the disease is caught early, the 5-year survival rates approach 70% among patients who can undergo liver transplantation. Liver resection and radio frequency ablation are also potentially curative; however, recurrence occurs in about 70% of patients 5 years after liver surgery.

Why isn’t HCC discovered early?

Hepatocellular carcinoma can be challenging to detect early because its signs and symptoms often do not appear until the more advanced stages of cancer. In addition, HCC usually coexists in a background of concurrent liver diseases, including viral hepatitis and nonalcoholic fatty liver disease (NAFLD), which may complicate diagnosis.

Despite these challenges, it is imperative to discover HCC as early as possible while curative treatment approaches are still available to the patient.

People at risk for HCC can be identified

The risk factors for HCC among people living in the United States include well- established causes and recently emergent determinants of disease. Cirrhosis caused by chronic liver disease increases a patient’s risk for HCC, although in many cases the risk can be reduced when chronic liver disease is managed to prevent cirrhosis.

Risk factors that increase the probability of cirrhosis and HCC

• Chronic hepatitis B virus (HBV) infection is the most common cause of HCC throughout the world today, although it is not as prevalent in the United States. Most cases of HBV infection-related HCC occur in patients who have cirrhosis; however, HBV can cause HCC without cirrhosis
• Chronic hepatitis C virus (HCV) infection is more common in the United States than HBV infection. Hepatocellular carcinoma often develops in a background of HCV-induced cirrhosis
• Chronic alcohol abuse is an all too frequent cause of HCC. The risk leading to alcohol-related HCC is a modifiable and preventable determinant of disease
• Nonalcoholic fatty liver disease has recently emerged as an important risk for HCC. As many as 20% of HCC cases in the United States are thought to be related to NAFLD
  • Nonalcoholic fatty liver disease has become the fastest-growing cause of HCC and HCC-related liver transplantation
• Smoking, diabetes mellitus, and obesity are also relevant modifiable risk factors for HCC

Increase utilization, improve effectiveness

Surveillance for HCC is underutilized.

• In the United States, only one third of the estimated 3 million patients who meet the criteria for surveillance receive it

Underutilization is driven, in part, by physician- and patient-related barriers to surveillance.

• Primary care physicians may harbor misconceptions about surveillance and may have concerns about cost-effectiveness in patients who do not have cirrhosis
• As many as half of patients report that scheduling, cost, and transportation barriers stand in their way

Today’s conventional surveillance relies on two tools that aren’t sensitive enough to be highly effective:

• Ultrasound imaging, when used in combination with a blood test for alpha- fetoprotein (AFP), is only 63% sensitive in detecting HCC early in patients who actually have HCC
• When ultrasound imaging is used alone, its sensitivity falls to 47%
  • Surveillance with AFP alone misses most early-stage HCC