Hepatitis B virus infection is a serious health problem in the Asia-Pacific region. It has been estimated that, globally, around 350 million people are chronic hepatitis B carriers and 1 million people die annually from hepatitis B-related diseases including chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma (HCC). In Taiwan, hepatitis B infection is an important cause of chronic hepatitis, cirrhosis of the liver, and HCC. Prior to the introduction of the national hepatitis B vaccination program in Taiwan in 1984, the hepatitis B surface antigen (HBsAg) carrier rate among the general Taiwanese population ranged from 15% to 20%. Till 2012, hepatitis B-related diseases are still ranked as the leading causes of death in Taiwan. In order to tackle this health problem, an universal hepatitis B vaccination program for newborns was launched. At the commencement of the program, the HB carrier rate amongst children less than 12 years of age was 9.8%. As time has passed following program inception, a number of follow-up studies have indicated that both the hepatitis B infection and carrier rates have declined progressively and continuously.
　　Diagnosis of hepatitis B infection, in addition to the neonatal hepatitis B vaccination program, continues to play an important role in preventing hepatitis B infection. However, the hepatitis B diagnostic methods used differ between developed and developing countries and between countries with high and low levels of endemic hepatitis B infection. In some developed countries like the USA, ongoing hepatitis B infection is diagnosed by the HBsAg and a confirmatory test. Such a practice is feasible in developed countries where the hepatitis B infection rate is low (<3%). On the other hand, in developing countries such as Taiwan, where hepatitis B infection is endemic, the protocol of diagnosing current hepatitis B virus infection using only HBsAg has been carried out for more than 20 years. However, Taiwan is currently changing from a country with high endemic hepatitis B infection to one that has a low level of endemic hepatitis B infection. As the prevalence of hepatitis B infection among younger generations has decreased, additional confirmation steps may become cost-effective, which is similar to the situation when testing for antibodies against other viruses, such as hepatitis C virus (HCV) and human immunodeficiency virus (HIV). False-positive results often result in unnecessary clinical follow-up studies, anxiety, and social stigma as well as financial expense. Hence, it is worthwhile to reevaluate the efficacy of screening and diagnosing hepatitis B infection using only HBsAg, a practice which has been carried out for more than 20 years in Taiwan. As expected, a significant decrease in the true-positive rate of HBsAg among the students born after the introduction of hepatitis B vaccination was observed only when HBsAg testing was applied. Additional neutralization tests may therefore become mandatory for persons with a positive HBsAg test result who were born after the commencement of the universal neonatal hepatitis B vaccination program in Taiwan.
　　In addition to the after-mentioned increasing proportion of HBsAg false-positivity after hepatitis B vaccination era, there are still several other clinical scenarios concerning the meaning and interpretation of HBsAg that might be confusing to clinicians. For example, the diagnostic false-positive after hepatitis B vaccination, and occult hepatitis B infection (i.e., hepatitis B DNA-positivity in case of HBsAg-negativity), etc. Cases will be cited to demonstrate the clinical application and interpretation.