Hepatocellular Carcinoma: A Global View: Incidence
Ju Dong Yang, MD; Lewis R. Roberts, MD, PhD Faculty and Disclosures
CME Released: 07/13/2010; Valid for credit through 07/13/2011
INCIDENCE
In 2008, an estimated 748,000 new cases of liver cancer occurred and approximately 696,000 people died of this cancer worldwide,[1] an increase from 626,000 new liver cancers and 598,000 deaths from liver cancer in 2002.[2] The numbers of incident cases and liver cancer deaths are similar because most HCCs are detected at an advanced stage in patients with underlying liver dysfunction, making this a highly lethal cancer. The incidence of liver cancer varies around the world ( Table 1 ), and is highest in Mongolia (116.6 cases per 100,000 person-years for men; 74.8 cases per 100,000 person-years for women).[1] Over 80% of HCCs occur in developing countries in sub-Saharan Africa, southeast Asia, and East Asia (including Mongolia). By contrast, the incidence of HCC is much lower in developed countries in North America (6.8 cases per 100,000 person-years for men; 2.2 cases per 100,000 person-years for women), Europe (except for southern Europe), Central and South America, Australia and New Zealand.[1] Global variations in incidence rates of this cancer closely reflect the variation in risk factors for HCC; thus, countries with a high prevalence of HBV or HCV infections usually have a high incidence of HCC (Figure 1). This finding is consistent with the fact that about three-quarters of HCCs are attributed to chronic HBV and HCV infections.
Figure 1.
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Global Variations in Age-adjusted Incidence Rates of Liver Cancer, Prevalence of Chronic HCV Infection and Chronic HBV Infection. Maps were generated using incidence rates of liver cancer from GLOBOCAN 2002;2 prevalence of chronic HBV infection from US Centers for Disease Control and Prevention;106 and prevalence of chronic HCV infection from WHO International Travel and Health.107
During 1978-1992, the incidence of liver cancer increased in developed countries and decreased in developing countries.[3] For example, in the USA, the incidence of HCC tripled over the 30 years from 1975 to 2005 (from 1.6 cases to 4.9 cases per 100,000 of the population).[4] The increase in number of patients with chronic hepatitis C who became infected between 1960 and 1990 in developed countries is believed to drive this trend, which is expected to peak around 2015-2020 and then gradually decline.[5,6] As HCV is the most common risk factor for HCC in the USA, if HCV-related HCCs decrease, HCCs overall are expected to decrease as well. In contrast to the decreasing contribution of chronic hepatitis C, the increasing prevalence of the metabolic syndrome, diabetes mellitus and nonalcoholic steatohepatitis (NASH) are all expected to continue to contribute to increased rates of HCC in the USA for the foreseeable future.[7] The increased immigration of people from populations at high risk of HCC into developed countries also contributes to the rising trend in incidence rates of HCC in the USA and European countries.
The age at which HCC develops in individuals infected with HBV or HCV is closely related to their age at acquisition of infection and the rate of active viral replication. In West Africa, HBV infection is generally acquired between the ages of 1 and 5 years, and viral replication declines rapidly after adolescence. In this region, the incidence of HCC stabilizes after age 45 years, although this observation might not take into account that some individuals infected with HBV die from other causes before they develop HCC. In East Asia, HBV infection is acquired before the age of 1 year in the majority of cases, and active HBV replication continues until an advanced age; therefore, the incidence of HCC continues to increase with age, without reaching a plateau (Figure 2).[8] The difference in the viral replication rates in West Africa compared with East Asia might be related to differences in host immunity or to differences in the viral genotypes found in these two regions. As a consequence of viral infection at an early age, affected individuals (especially in African countries) develop cancer in their mid-adulthood, during their most productive years of life. This situation results in a substantial burden on healthcare resources, as well as a drain of intellectual and productive capacity in the low-income and middle-income countries most affected by these diseases. Conversely, in countries where hepatitis B is not endemic, HBV and HCV infections are usually acquired in adulthood. In these countries, HCC rarely develops before the age of 50 years and the highest age-specific incidence rates are observed in people over age 75 years.[9]
Figure 2.
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Age-specific Incidence Rates of Hepatocellular Carcinoma Among Men in China and Gambia (West Africa). Data from GLOBOCAN, 2002.2
The risk of HCC is 2-7 times higher in men than in women, although this ratio varies across the world.[3,10] The explanation for this sex difference might be threefold: firstly, men could have higher rates of environmental exposure to liver carcinogens (such as smoking or alcohol) and hepatitis virus infections; secondly, estrogen effects might suppress interleukin (IL)-6-mediated inflammation in women, reducing both liver injury and compensatory proliferation; thirdly, testosterone effects could increase androgen receptor signaling in men, promoting liver cell proliferation.[
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