Incidence, Mortality, and Risk Factors
Hepatocellular cancer (HCC) is the fourth most common cancer in the world. Age-standardized incidence rates vary from 2.1 per 100,000 in North America  to 80 per 100,000 in China. In the United States, it is estimated that there will be 33,190 new cases diagnosed in 2014 and 23,000 deaths due to this disease. 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 22.1 per 100,000 and among women is 8.5 per 100,000 population. 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.[5,6,7] 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.
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%. Other risk factors include alcoholic cirrhosis, hemochromatosis, alpha-l-antitrypsin deficiency, glycogen storage disease, porphyria cutanea tarda, tyrosinemia, and Wilson disease, but rarely biliary cirrhosis. 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.