The Global Epidemiology of Hepatocellular Carcinoma: Present and Future

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Incidence and mortality

Because diagnostic confirmation of HCC is not routine worldwide, it is easier to examine incidences of primary liver cancer than incidences of HCC. However, because HCC is the most common histology in most countries, primary liver cancer rates are a close approximation of HCC rates. An exception is northeast Thailand, which has high rates of primary liver cancer (male incidence = 88/100,000; female incidence = 35/100,000)5 because of the exceptionally high incidence of intrahepatic

Risk factors

At least 80% of HCCs are associated with chronic infection with either of 2 viruses, HBV and HCV. Of these, HBV infections account for 75% to 80% of virus-associated HCCs, with HCV responsible for 10% to 20%.9 Other risk factors include consumption of aflatoxin B1 (AFB1) contaminated foodstuffs, excessive consumption of alcohol, diabetes/obesity, and certain rare metabolic disorders, such as hemochromatosis, α-1 antitrypsin deficiency, tyrosinemia, and several porphyrias. Although persons with

HBV

Several pathologists proposed in the 1950s that chronic virus infections of the liver could lead to liver cancer.13, 14, 15 They also noted the strong association between cirrhosis and liver cancer, because at least 80% of liver cancers occurred in cirrhotic livers. The cirrhosis-liver cancer link was suggested to be stronger in Asia and Africa, where 5% to 50% of men with cirrhosis developed liver cancer, whereas the percentage in the United States and Western Europe was 3% to 10%.15 In most

HCV

The HCV, an RNA virus of the Flaviviridae family, was identified in 1989.41 Reliable serologic tests for antibody to HCV (anti-HCV) became available in 1990, and in 1994 the International Agency for Research on Cancer (IARC) classified HCV as carcinogenic to humans.16 Unlike the HBV, HCV has not been shown to infect nonhuman hosts in the wild.

Phylogenetic analysis of HCV has identified at least 6 major genotypes (numbered 1–6) and numerous subtypes (denoted by lowercase letters).42, 43

Aflatoxin

Aflatoxin, a mycotoxin produced by molds of Aspergillus species (Aspergillus flavus and Aspergillus parasiticus), contaminates maize, groundnuts, and tree nuts in warm, humid environments and is a well-established hepatic carcinogen.59 Aflatoxin exposure has likely been prevalent in human populations throughout history. There are 4 principal aflatoxins (B1, B2, G1, and G2), of which aflatoxin B1 (AFB1) has been shown to be the most potent in animal studies.59 Based largely on the indisputable

Alcohol

In 1988, IARC concluded that there was a causal relationship between alcohol consumption and liver cancer.70 In 2007, the World Cancer Research Fund and American Institute for Cancer Research, in a review of diet and physical activity studies, concluded that alcohol consumption was probably a direct cause of liver cancer.71

Most studies in low-risk HCC populations have found alcohol to be a significant risk factor,72, 73, 74, 75, 76, 77, 78, 79, 80 whereas the evidence from earlier studies in

Obesity, diabetes mellitus and nonalcoholic steatohepatitis

A significant relationship between diabetes and liver cancer was first reported in 1986.100 Although several early epidemiology studies101, 102 did not confirm the relationship, later studies, with a few exceptions,103, 104 were confirmatory. The bulk of the literature, summarized in systematic reviews105, 106 and meta-analyses,107 now provides strong evidence from low-risk, intermediate-risk, and high-risk countries that HCC and diabetes are significantly associated.

Many of the studies in

Summary

The global risk of HCC has been largely driven by HBV infection for the past century. Contributions to risk have also been made by other factors, including HCV, aflatoxin, excessive alcohol consumption, and obesity/diabetes. The dominant effect of HBV on global HCC risk should decline in future generations as the population vaccinated against HBV advances in years. Infection with HCV should also decline as a major cause of HCC in future generations because HCV was removed from the blood supply

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      Citation Excerpt :

      The occurrence of HCC is attributed to various risk factors, and essential ones are chronic infections of hepatitis B (HBV) and hepatitis C virus (HCV) [2]. The number of cases of virus-induced HCC is especially high in East Asia, especially in China, which accounts for more than 80% of the total cases worldwide [3]. Male sex has long been recognized as a prominent risk factor for HCC depending on various countries or regions.

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    This work was supported by funding of the NCI Intramural Research Program.

    The authors have nothing to disclose.

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