Infections from hepatitis A virus (HAV) and hepatitis B virus (HBV) are significant problems in Alaska Natives. Hepatitis A and B vaccines have been routine immunizations in Alaska Natives since 1984 and 1994, respectively. Hepatitis A vaccine is administered to all children over 1 year of age in the US and catch-up hepatitis A virus (HAV) vaccine programs are employed in several states for all children. Hepatitis B vaccine has been administered to all neonates and children in the US for the past decade and to high risk individuals. In addition, chronic hepatitis B and C infections are significant causes of morbidity and mortality from hepatocellular carcinoma (HCC) and cirrhosis in high risk populations in the US. Alaska Natives have one of the highest rates of chronic HBV infection of any ethnic group in the US and a high rate of morbidity and mortality from hepatitis C infection. Not all persons with chronic hepatitis B or C will develop cirrhosis or HCC and the risk factors for progression are not completely elucidated. Population studies are needed to study risk factors for progression of chronic HBV and HCV. The Liver Disease and Hepatitis Program (LDHP) of the Alaska Native Tribal Health Consortium (ANTHC) working collaboratively with the Arctic Investigations Program (AIP) of the Centers for Disease Control and Prevention (CDC) has cohorts of persons who received hepatitis A and B vaccine as infants, children and adults available to determine long-term protection. In addition, the LDHP has recruited large cohorts of Alaska Natives with chronic hepatitis B or C infection. Relevance The strategy and cost effectiveness of hepatitis A and B vaccination programs depends on the supposition that these vaccines will provide long-term protection against hepatitis A and B infection. Also of concern is that persons with chronic hepatitis B or C infection are at-risk to cirrhosis and other serious liver disease. Using several Alaska Native cohorts, studies are proposed to (a) determine the duration of protection against hepatitis A and B infection in persons immunized 15-30 years ago and (b) better understand the treatment and natural history of chronic hepatitis B or C infection.