Heavy Alcohol Use: Heavy alcohol use (definitions for this vary by study) has also been shown to correlate with HCC risk.Male Sex at Birth: The risk of HCC is elevated in men, at an approximately 2- to 4-fold higher risk compared with women.Further, a study in the United States that utilized national Veterans Administration data showed that even in the absence of cirrhosis HCC risk was high among persons with chronic HBV who had high alanine aminotransferase (ALT) levels and were older than 40 years of age, irrespective of their race. Older Age: Multiple studies from different regions of the world have shown that older persons with chronic HBV have a significantly higher risk of developing HCC than younger persons with chronic HBV.In addition to liver disease severity, a number of other factors have been associated with an increased risk of HCC: Most studies involving persons with HBV, however, have shown that the risk of HCC is orders of magnitude higher in the presence of cirrhosis in both treated and untreated individuals. The integration of HBV DNA into the host cellular genome, which can induce genetic damage and stimulate HBV-associated immune-mediated changes in the liver microenvironment, is thought to be a contributing factor in hepatocarcinogenesis. In contrast to chronic hepatitis C virus (HCV)-related HCC, where cirrhosis is nearly ubiquitous, HBV is unique in its ability to promote tumorigenesis in the absence of cirrhosis through a variety of oncogenic mechanisms. The immune-mediated changes in the liver microenvironment and genetic damage induced by integration of HBV DNA into the host genome are thought to be contributing factors in hepatocarcinogenesis. The reported HCC incidence in persons with cirrhosis is 2.2 to 4.3 per 100 person-years versus 0.1 to 0.8 per 100 person-years in those without cirrhosis. Ĭirrhosis from any cause is an important risk factor for HBV-associated HCC and for HCC overall. The liver cancer and intrahepatic bile duct cancer death rates in the United States varied significantly among different racial and ethnic groups ( Figure 7). In 2019, men had a much higher incidence of HCC than women, with an age-specific rate per 100,000 people of 12.6 among men versus 4.5 among women. The age-adjusted death rates for liver cancer increased at an average of 0.8% per year in the United States from 2011-2020, with 88% of the deaths occurring among those older than 55 years of age. The number of liver cancer deaths in the United States has steadily increased from 1999 through 2019, with 27,958 liver cancer deaths in 2019 ( Figure 6). In 2019, liver cancer was the sixth leading cause of cancer deaths in the United States ( Figure 5). The rates of liver cancer and intrahepatic bile duct cancer in the United States vary significantly among different racial and ethnic groups ( Figure 4). In 2019, there were an estimated 35,563 liver and intrahepatic bile duct cancer cases reported in the United States, according to the U.S. The annual number and rate of new liver cancer cases have overall increased during the past 20 years, which is consistent with the advancing age of the United States population, though the number of cases and rate has leveled off since 2014 ( Figure 3). In the United States, the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI) combine liver cancer and intrahepatic bile duct cancer under "liver cancer", but HCC represents 75 to 90% of these total liver malignancies. Individuals with chronic HBV infection can carry a 20- to 60-fold increased risk of HCC compared to individuals without HBV infection. Globally, chronic infection with hepatitis B virus (HBV) is the leading cause of liver cancer. This geographic disparity is likely attributable in large part to the higher prevalence of chronic hepatitis B virus (HBV) infection in Asia and Africa. In 2020, the age-standardized incidence rates for liver cancer were highest in Eastern Asia and Northern Africa, at 17.8 and 15.2 cases per 100,000 persons, respectively, whereas the United States fell into the higher intermediate category with an age-standardized rate of 6.9 cases per 100,000 persons. Liver cancer or hepatocellular carcinoma (HCC) is the sixth most common malignancy ( Figure 1) and the third leading cause of cancer-related deaths worldwide ( Figure 2).
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