Rising Incidence of Hepatocellular Cancer in the United States

Author: El-Serag, HB and Mason, AC
Content Contributor: Abramson Cancer Center of the University of Pennsylvania
Last Reviewed: November 01, 2001

Reviewers: Kenneth Blank, MD
Source: The New England Journal of Medicine March 11, 1999 Vol. 340 No 10 p.745


Hepatocellular (liver) cancer is one of the most common tumors in the world, with the highest incidence in third world countries. Several recent,small reports suggest that the incidence of this deadly cancer is rising in the United States. To investigate whether the incidence of hepatocellularcancer is truly rising in the United States, researchers from the University of New Mexico conducted a study to determine current incidence of andmortality from hepatocellular cancer in the 1990s. Trends across time by ethnic and age groups were also examined.

Materials and Methods

The authors analyzed three large national databases to determine the incidence of and mortality from hepatocellular cancer. The three databases were:1) the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute which tracks cancer rates from several statesand metropolitan areas, accounting for 14% of the US population; 2) the National Center for Health Statistics vital statistics database which consistsof all death certificates issued in the United States; and 3) the Veterans Administration database of records of all inpatients at the nation's 172Veterans Administration hospitals.


The incidence of hepatocellular cancer has risen significantly over the last three decades. The incidence of hepatocellular cancer was 1.4 per 100,000from 1976 to 1980 and rose to 2.4 per 100,000 from 1991 to 1995. The incidence of hepatocellular cancer rose substantially in men, especially inblack men. Among black men, the incidence of hepatocellular cancer increased 4.0 to 6.1 per 100,000 between the time periods 1976 through 1980to 1991 through 1995. Age-specific incidence analysis revealed hepatocellular cancer to be affecting younger patients more commonly in the 1990scompared to the two prior decades.

The trends in mortality from hepatocellular cancer paralleled the trends in incidence. Overall there was a 41% increase in mortality from the 1970s tothe 1990s. The age-adjusted mortality rate for black men increased from 5.3 per 100,000 from 1981-1985 to 6.0 per 100,000 from 1991-1995. Therates of mortality in white men over these same time periods rose from 2.3 to 3.4 per 100,000. The increase in mortality in women was considerablysmaller.


Trend analyses clearly indicate an increase in hepatocellular cancer, particularly among the young and in black males. Why this increase? Onepossible explanation is a rise in the incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV). There is strong epidemiological evidence thatnearly all hepatocellular cancer is caused by these two viruses (HBV and HCV). The worldwide distribution of hepatocellular cancer is similar to thedistribution of HBV and HCV. Moreover, the risk of hepatocellular cancer increases 100 fold in patients with chronic HBV or chronic HCVinfection compared with uninfected controls.

The process by which HBV and HCV cause liver cancer is not well understood. One hypothesis asserts that the viruses initiate a cycle ofinflammation, cellular damage and repair which eventually leads to fibrosis (cirrhosis) of the liver, and ultimately, hepatocellular cancer. The virusalso produces a protein, which can stimulate cellular growth, and the viral genome has been shown to integrate into the DNA of hepatocytes causinginstability and gene mutations. This etiologic hypothesis has led to several strategies to reduce the transmission of HBV and HCV.

A vaccine against HBV has been developed and a study in Taiwan found that vaccinating children reduced the incidence of HBV and hepatocellularcancer. In the United States the screening of blood products has reduced the risk of transfusion-induced HCV infection to 1 in 100,000. Treatmentof infected patients with interferon alpha or ribavirin has yielded encouraging results. With the advent of these anti-viral medications and vaccinationsthe incidence of chronic HCV and HBV infection will surely decline, and with it the incidence of hepatocellular cancer.

Patients with chronic HBV or chronic HCV infection should be monitored with serial alpha-fetoprotein measurements and liver ultrasound to detecthepatocellular cancer at an early stage. However, the frequency with which these screening tests should be performed is controversial, and it remainsto be seen whether early detection will improve outcome.

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