To the Editor:

We read with interest the article on a large case-control study that a hepatitis B surface antigen (HBsAg) level <200 IU/mL is predictive of HBsAg seroclearance within 3 years.1 Their results confirmed our earlier observation that serum HBsAg level ≤200 IU/mL has a negative predictive value (NPV) of 100% and 92% for HBsAg seroclearance at 1 and 3 years, respectively, with a positive predictive value (PPV) of 97% and 100% if combined with a ≥1 log10 IU/mL reduction in the preceding 2 years.2 Both studies have shown that HBsAg level <200 IU/mL is an optimal level for the prediction of HBsAg seroclearance at 1 and 3 years. Interestingly, Seto et al.1 further showed that a 0.5 log reduction in HBsAg during the next year in those with serum HBsAg >200 IU/mL may predict HBsAg seroclearance in 3 years with a sensitivity of 74% and a specificity of 89.4%.1 Reanalyzing our data also showed that an HBsAg decline of 1 log10 IU/mL in the following 2 years (equivalent to 0.5 log/year) had an NPV of 98% and a PPV of 67% for HBsAg seroclearance. Using the receiver operating characteristic and the area under curve (0.966; 95% confidence interval [CI] 0.915-1.000; P < 0.001), 2-year HBsAg decline of 1 log (0.5 log/year) is a good predictor for HBsAg seroclearance in those with HBsAg >200 IU/mL.

Prediction of HBsAg seroclearance using HBsAg levels has attracted much attention recently. Two Asian studies used an HBsAg level <100 IU/mL as a remote predictor of HBsAg seroclearance within 6 to 10 years.3, 4 Obviously, prediction of spontaneous HBsAg seroclearance within a much shorter period of 1-3 years, using an HBsAg level of 200 IU/mL,1, 2 is more useful in daily clinical practice.


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  • 1
    Seto W-K, Wong DK, Fung J, Hung IF, Fong DY, Yuen JC, et al. A large case-control study on the predictability of hepatitis B surface antigen (HBsAg) levels three years before HBsAg seroclearance. HEPATOLOGY 2012 DOI: 10.1002/hep.25718. Article first published online: 10 JUL 2012.
  • 2
    Chen YC, Jeng WJ, Chu CM, Liaw YF. Decreasing levels of HBsAg predict HBsAg seroclearance in patients with inactive chronic hepatitis B virus infection. Clin Gastroenterol Hepatol 2012; 10: 297-302.
  • 3
    Chan HL, Wong GL, Tse CH, Chan HY, Wong VW. Viral determinants of hepatitis B surface antigen seroclearance in hepatitis B e antigen-negative chronic hepatitis B patients. J Infect Dis 2011; 204: 408-414.
  • 4
    Tseng TC, Liu CJ, Su TH, Wang CC, Chen CL, Chen PJ, et al. Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology 2011; 141: 517-525.

Yi-Cheng Chen M.D.*, * Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.