Observational studies show that among perinatally-infected individuals, incidence of HCC begins rising in young adulthood (20±30 years of age). Among those who are infected later in life the incidence of HCC begins rising at 40 to 50 years of age. Other major risk factors for HCC include presence of cirrhosis, e-antigenemia, exposure to other hepatotoxins including alcohol and tobacco, and co-infection with hepatitis C virus. HCC screening is usually done at 6±12 month intervals. Common modalities used include serum alpha fetal protein (AFP), ultrasound (US), and computed tomography (CT). The usefulness of AFP is limited by sensitivity (approximately 60%) and specificity (approximately 85%). Thus, US or CT must be used in conjunction with AFP. Ultrasound, the most widely-used modality, has a variable sensitivity determined by operator experience, reported to be 35% to 84%. CT, with less operator-dependent variability and sensitivity greater than 90%, is the most expensive of screening modalities. Given the limitations of existing screening methods and overall small survival-benefits of current widely-available treatments, the cost-effectiveness of HCC screening has been questioned. There are no randomized studies assessing cost-effectiveness of HCC screening. Non-randomized studies have shown conflicting results. Thus, although a recent survey of U.S. hepatologists showed that 84% of respondents screen for HCC in individuals with cirrhosis, no official guidelines have yet been provided by the National Cancer Institute (NCI).