Hepatitis.

ically infected with hepatitis C virus (HCV) and another 350 million individuals are chronically infected with hepatitis B virus (HBV) (1,2). Canada is estimated to have 240,000 to 300,000 HCV and 200,000 to 280,000 HBV chronic carriers (3,4). Without intervention, over multiple decades, approximately 15% to 30% of chronic HBVand HCV-infected individuals will develop cirrhosis, end-stage liver disease or liver cancer, or will require liver transplantation (1,2,5). From a public health perspective, the major challenge is how best to avoid acute (incident) infections in at-risk populations, and for those already chronically infected, how to prevent consequent morbidity and mortality. For HCV, primary prevention is difficult, because a vaccine is not available nor is one likely to be available in the near future. Although the blood product transmission of HCV has been virtually eliminated by the effective serological screening of blood donors, parenteral substance abuse continues to be the major source of ongoing transmission (6-8). Despite the lack of a HCV vaccine, new and effective but costly HCV treatments (interferon, pegylated interferons with and without ribavirin) can cure (ie, eliminate HCV RNA from the body) in 30% to 90% of treated individuals (1). Recently Jaeckel et al (9) reported that the early treatment of acute HCV with interferon monotherapy prevented chronic infection in 98% of treated cases. The efficacy of currently available treatments for HCV will drive future demands for treatment and the ensuing costs. Recent estimates suggest that the cost of HCV to our health care system is similar to the cost of asthma, or approximately US$5.4 billion/year in the United States (10). For HBV, a safe and effective vaccine is available for primary prevention, but many decades of population-based vaccination will be required before the entire population is adequately protected because of the large numbers of chronic carriers in the global population (11). HBV vaccine escape mutants have been described; these refer to mutations in the hepatitis B surface antigen that may result in failed protection from the current HBV vaccine (12,13). In some cases, this may affect the ability of current enzyme immunoassays to detect active infection, ie, hepatitis B surface antigen in serum or plasma (12,13). Clearly, surveillance systems need to be in place to ensure that HBV vaccines remain effective and that vaccine escape mutants do not replace current HBV strains. Treatment for HBV is also evolving rapidly (eg, lamivudine, adefovir dipivoxil, entecavir, fluorothiacytidine and interferons) (14). Both lamivudine and interferon can suppress HBV viral replication and improve the outcome of chronic HBV infection. Typically, 15% to 50% of treated HBV patients have a durable response after interferon or long term lamivudine treatment, but unlike HCV, complete viral elimination from the body may not be possible, because viral DNA is incorporated into the host genome (5). The patient seroconverting from being hepatitis B e antigen-positive to being anti-hepatitis B e antigen-positive typically indicates treatment response. The complete loss of hepatitis B surface antigen is rare, generally occurring less than 10% of the time (2,5). Some patients, however, may have viral mutations (eg, precore mutations) that prevent the expression of hepatitis B e antigen. For these patients, HBV DNA tests are required to monitor treatment response (5). At this point in time, there is a pressing need for more standardized serological and/or nucleic acid tests, or other markers that predict the patients who are most likely to have a durable treatment response and/or that define the optimal treatment duration (15-17). Another challenge to clinicians is that lamivudine monotherapy is associated with the rapid emergence of antiviral resistance in 15% to 60% of treated individuals. Therefore, the utility of combination therapy needs to be investigated (14-16). For hepatitis A virus (HAV) infection, while it does not result in chronic disease, its public health impact relates to its ease of transmission (fecal-oral), the rare occurence of fulminant hepatitis and the fact that HAV shares some common