The Korean Journal of Hepatology 2010;16:342-346 DOI: 10.3350/kjhep.2010.16.3.342 The Korean Journal of Hepatology Elsewhere Growing attention to an old marker, hepatitis B surface antigen, in the natural history of chronic hepatitis B Jeong Won Jang Department of Internal Medicine, College of Medicine, WHO Collaborating Center on Viral Hepatitis, The Catholic University of Korea, Seoul, Korea Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Thompson AJ, Nguyen T, Iser D, Ayres A, Jackson K, Littlejohn M, Slavin J, Bowden S, Gane EJ, Abbott W, Lau GK, Lewin SR, Visvanathan K, Desmond PV, Locarnini SA. Hepatology 2010;51:1933-1944. Hepatitis B surface antigen (HBsAg), originally referred as to “Australia antigen” was discovered approximately 40 years ago. Over the years, the presence of this antigen has remained the hallmark of hepatitis B virus (HBV) infection. HBsAg is the viral envelope and is composed by 3 proteins, such as S (small, S domains), M (medium, preS2+S) and L (large, preS1+preS2+S) codified by only one open reading frame. The S-HBs protein is the major component of the virion envelope and the subviral HBsAg particles, such as filaments and spheres, while virions and filaments contain more M-HBs, and in particular, more L-HBs proteins than spheres.1,2 In infected individuals, subviral particles are present in at least 100-fold excess over virions.3 The processing of production and secretion of HBsAg is complex, and the comparative proportion of each S-, M-, L-HBsAg component in the serum and liver varies according to the state of HBV replication.4 The recent growing interest in quantitative analysis of HBsAg as a clinical parameter has been based on several studies that observed its relationship with serum and liver HBV DNA.5-7 In fact, quantification of HBsAg was introduced more than 20 years ago, but its clinical usefulness has been questioned due to the lack of appropriate standardization.8 Consequently, HBsAg has long been used typically as a qualitative marker for diagnosing an ongoing HBV infection. Recently, a quantitative, fully automated chemiluminescent microparticle immunoassay for the detection of HBsAg became available and offered more reliable quantitative data for HBsAg at a wide range of concentrations.5 It has been suggested that serum HBsAg levels correlate well with intrahepatic amounts of total HBV DNA and covalently closed circular DNA (cccDNA), which is responsible for viral persistence.6,7 Furthermore, reduction in HBsAg serum levels reportedly provided good predictive ability in patients treated with antiviral therapy. In HBeAg-negative individuals, serum HBsAg levels <10 IU/mL at week 48 and on-treatment decline >1 log IU/mL have been significantly associated with sustained HBsAg clearance 3 years after treatment, while a decrease of 0.5 log IU/mL and 1 log IU/mL in HBsAg levels at weeks 12 and 24 of therapy, respectively, have high predictive values of a sustained virologic response.9,10 Although these results suggest the potential clinical usefulness of quantitative HBsAg as an on-treatment predictor, such a good correlation was only observed in the setting of immunomodulatory agents (pegylated interferon therapy).9,10 Thus, whether or not HBsAg serum levels are still efficient as a marker for on-treatment prediction for Keywords: Hepatitis B virus; Hepatitis B surface antigen; Chronic hepatitis B; Korea Abbreviations: HBsAg, Hepatitis B surface antigen; HBV, hepatitis B virus; cccDNA, covalently closed circular DNA Corresponding author: Jeong Won Jang Department of Internal Medicine, Incheon St. Mary’s Hospital, 665 Bupyeong 6-dong, Bupyeong-gu, Incheon 403-720, Korea Tel. +82-32-510-5682, Fax. +82-32-510-5683, E-mail; garden@catholic.ac.kr Copyrights Ⓒ 2010 by The Korean Association for the Study of the Liver The Korean Journal of Hepatology∙pISSN: 1738-222X eISSN: 2093-8047