Incidence, Mortality, and Risk Factors

Incidence, Mortality, and Risk Factors

Hepatocellular cancer (HCC) is the fourth most common cancer in the world.[1] Age-standardized incidence rates vary from 2.1 per 100,000 in North America [2] to 80 per 100,000 in China.[1] In the United States, it is estimated that there will be 21,370 new cases diagnosed in 2008 and 18,410 deaths due to this disease.[3] There is a distinct male preponderance among all ethnic groups in the United States, although this trend is most marked among Chinese Americans, in whom the annualized rate of HCC among men is 20.9 per 100,000 and among women is 8.0 per 100,000 population.[4] Chronic hepatitis B and C are recognized as the major factors worldwide increasing the risk of HCC, with risk being greater in the presence of coinfection with hepatitis B virus and hepatitis C virus.[5-7] The incidence of HCC in individuals with chronic hepatitis is as high as 0.46% per year. In the United States, chronic hepatitis B and C account for about 30% to 40% of HCC. Chronic hepatitis G infection is not associated with HCC in either hepatitis B surface antigen–positive carriers or noncarriers.[8]

Cirrhosis is also a risk factor for HCC, irrespective of the etiology of the cirrhosis. The annual risk of developing HCC among persons with cirrhosis is between 1% and 6%.[6] Other risk factors include alcoholic cirrhosis, hemochromatosis, alpha-l-antitrypsin deficiency, glycogen storage disease, porphyria cutanea tarda, tyrosinemia, and Wilson disease,[2] but rarely biliary cirrhosis.[9] A retrospective case-control study found that features suggestive of nonalcoholic steatohepatitis, including obesity, type 2 diabetes, dyslipidemia, and insulin resistance, were more frequently observed in patients with HCC associated with cryptogenic cirrhosis than in those with HCC of viral or alcohol etiology.[10,11] Aflatoxins, which are mycotoxins formed by certain Aspergillus species, are a frequent contaminant of improperly stored grains and nuts. In parts of Africa, the high incidence of HCC in humans may by related to ingestion of foods contaminated with aflatoxins. This association, however, is blurred by the frequent coexistence of hepatitis B infection in those population groups. The likely etiology of HCC is summarized in the following table.[12]

References

1. Parkin DM, Whelan SL, Ferlay J, et al., eds.: Cancer Incidence in Five Continents. Volume VII. Lyon, France: International Agency for Research on Cancer, 1997. 
   
   
2. Di Bisceglie AM, Carithers RL Jr, Gores GJ: Hepatocellular carcinoma. Hepatology 28 (4): 1161-5, 1998.  [PUBMED Abstract]
   
   
3. American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed October 1, 2008. 
   
   
4. Ries LAG, Harkins D, Krapcho M, et al.: SEER Cancer Statistics Review, 1975-2003. Bethesda, Md: National Cancer Institute, 2006. Also available online. Last accessed October 07, 2008. 
   
   
5. Benvegnù L, Fattovich G, Noventa F, et al.: Concurrent hepatitis B and C virus infection and risk of hepatocellular carcinoma in cirrhosis. A prospective study. Cancer 74 (9): 2442-8, 1994.  [PUBMED Abstract]
   
   
6. Ikeda K, Saitoh S, Koida I, et al.: A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology 18 (1): 47-53, 1993.  [PUBMED Abstract]
   
   
7. Chiaramonte M, Stroffolini T, Vian A, et al.: Rate of incidence of hepatocellular carcinoma in patients with compensated viral cirrhosis. Cancer 85 (10): 2132-7, 1999.  [PUBMED Abstract]
   
   
8. Yuan JM, Govindarajan S, Gao YT, et al.: Prospective evaluation of infection with hepatitis G virus in relation to hepatocellular carcinoma in Shanghai, China. J Infect Dis 182 (5): 1300-3, 2000.  [PUBMED Abstract]
   
   
9. Farinati F, Floreani A, De Maria N, et al.: Hepatocellular carcinoma in primary biliary cirrhosis. J Hepatol 21 (3): 315-6, 1994.  [PUBMED Abstract]
   
   
10. Bugianesi E, Leone N, Vanni E, et al.: Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 123 (1): 134-40, 2002.  [PUBMED Abstract]
    
    
11. Fattovich G, Stroffolini T, Zagni I, et al.: Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 127 (5 Suppl 1): S35-50, 2004.  [PUBMED Abstract]
    
    
12. Shiratori Y, Yoshida H, Omata M: Management of hepatocellular carcinoma: advances in diagnosis, treatment and prevention. Expert Rev Anticancer Ther 1 (2): 277-90, 2001.  [PUBMED Abstract]
    
    

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