Hepatocellular carcinoma: Recent trends in the United States
Section snippets
Incidence
Most of the information provided on the incidence of HCC is derived from publications that used the Surveillance Epidemiology and End Results (SEER) program as their data source.1 SEER is an ongoing contract-supported program of the National Cancer Institute to collect population-based cancer incidence and survival data. Since 1992, the SEER program has collected data on incident cancer cases from 11 population-based cancer registries in 5 states (Connecticut, Hawaii, Iowa, New Mexico, and
Secular (temporal) trends in the incidence of HCC
The age-adjusted incidence rates (using the standard population in 2000) of HCC increased 2-fold between 1985 and 19983, 4 (Figure 1). The average yearly, age-adjusted rate of HCC verified by histology or cytology increased from 1.3 per 100,000 persons during 1978–1980 to 3.0 per 100,000 persons during 1996–19984 (this study reported findings from 9 SEER registries; similar findings were obtained from 11 SEER registries). The increase in HCC began in the mid-1980s, and the greatest proportional
Mortality
According to the vital statistics of the entire United States, the age-adjusted mortality rates (standard population in 2000) of primary liver cancer increased from 2.8 per 100,000 persons in 1997 to 4.7 per 100,000 persons in 2001. These rates pertain to a definition that potentially included intrahepatic cholangiocarcinoma and tumors not specified as primary or secondary (ICD-9 155 and ICD-10 C22). If a more strict definition that specifically excludes cholangiocarcinoma is used (155.0 and
Hospitalizations
Concurrent with the rising incidence and mortality of HCC, there has been a parallel increase in the hospitalization rates for HCC (unique patients hospitalized with HCC divided by total number of unique patients hospitalized because of any other reason) in Veterans Administration (VA) hospitals. The proportional rates of HCC in all VA hospitals increased from 2.9 to 4.1 per 10,000 hospitalizations between 1983 and 1997.4 A second study has reported an increase in the frequency of patients
Demographic features of HCC in the United States
Analysis of SEER data indicate that the mean age at the time of diagnosis of HCC is 65 years; 74% of cases occur in men; and the racial distribution of patients is 48% white, 15% Hispanic, 13% African American, and 24% other (predominantly Asian). The epidemiology of HCC in the United States is characterized by significant variations in incidence by age, gender, race, and geographic region.
HCC is rare before age 40 years, rises in incidence progressively thereafter, and reaches a peak between
Demographic features and temporal trends in HCC
Changes in the demographic structure of the underlying general population may explain the rising rates of HCC. For example, an increase in the number of elderly people, men, or immigrants from high-risk regions (such as Southeast Asia and sub-Saharan Africa) could lead to an increase in reported rates of HCC. However, none of these demographic changes appear to explain the rising rates of HCC in the United States. The magnitude of these ethnic and gender differences in HCC have remained largely
Temporal trends in survival with HCC
Overall, the survival of patients diagnosed with HCC remains very poor. The 1-year and 3-year relative survival rates (relative to survival of age- and sex-matched controls without cancer) of more than 3600 cases diagnosed in 11 SEER registries during 1998–2000 is 36% and 17%, respectively. These figures represent a small but still significant improvement over survival rates recorded during 1977 and 1996.11 The small improvement in the overall survival of patients with HCC in population-based
Risk factors for HCC in the United States
Major risk factors of HCC that are relatively common include hepatitis C virus (HCV), hepatitis B virus (HBV), and heavy alcohol consumption. Rare risk factors include hemochromatosis, α-1 anti-trypsin deficiency, and Wilson’s disease. Importantly, studies in the United States evaluating risk factors of chronic liver disease or HCC have failed to identify specific risk factors in a large proportion of patients. Furthermore, cryptogenic cirrhosis has been estimated to account for 5% to 30% of
Etiology of rising trends of HCC in the United States
Most cases of HCC develop in persons with advanced chronic liver disease, and, therefore, an increase in the number of persons living with cirrhosis is the likely explanation for the rising incidence of HCC. This has resulted from a combination of the rising incidence of cirrhosis because of HCV and to a lesser extent HBV, as well as a general improvement in the survival of patients with cirrhosis. The improved survival of patients with cirrhosis,30 with improvements in clinical management of
Temporal trends in risk factors among HCC cases
Three published studies and 1 study published in only abstract form have examined temporal changes in risk factors among patients with HCC in the United States.5, 6, 33, 34 Two studies were from single large referral centers from which the ascertainment of viral risk factors was based on serologic markers performed on all cases,5, 6 and the other 2 studies were from national databases in which risk factors were ascertained only from ICD-9 codes in billing claims or discharge records.33, 34 In
Future trends of HCC
Chronic hepatitis C is estimated to affect 1.5% of the U.S. population and leads to cirrhosis in 20% to 30% of them within 20 to 30 years; among whom, the annual rate of HCC is predicted to be 1% to 6%.35 Most data suggest that there was an epidemic of HCV infection in the United States beginning in the 1960s and reaching a peak in the 1980s. Persons 20 to 30 years of age at that time were at the highest risk of acquiring the infection.36 Transmission of HCV was attributable to injection drug
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Dr. El-Serag is a VA Health Services Research & Development Awardee (RCD00–013–2) and (IIR 02–293).