Quantitative hepatitis B surface antigen and hepatitis B e antigen titers in prediction of treatment response to entecavir

Authors

  • Jung Min Lee,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
    2. Department of Internal Medicine, CHA University, Seongnam-Si, Korea
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  • Sang Hoon Ahn,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
    2. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
    3. Liver Cirrhosis Clinical Research Center, Seoul, Korea
    4. Brain Korea 21 Project for Medical Science, Seoul, Korea
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  • Hyon Suk Kim,

    1. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
    2. Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
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  • Hana Park,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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  • Hye Young Chang,

    1. Liver Cirrhosis Clinical Research Center, Seoul, Korea
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  • Do Young Kim,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
    2. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
    3. Liver Cirrhosis Clinical Research Center, Seoul, Korea
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  • Seong Gyu Hwang,

    1. Department of Internal Medicine, CHA University, Seongnam-Si, Korea
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  • Kyu Sung Rim,

    1. Department of Internal Medicine, CHA University, Seongnam-Si, Korea
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  • Chae Yoon Chon,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
    2. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
    3. Liver Cirrhosis Clinical Research Center, Seoul, Korea
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  • Kwang-Hyub Han,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
    2. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
    3. Liver Cirrhosis Clinical Research Center, Seoul, Korea
    4. Brain Korea 21 Project for Medical Science, Seoul, Korea
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  • Jun Yong Park

    Corresponding author
    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
    2. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
    3. Liver Cirrhosis Clinical Research Center, Seoul, Korea
    • Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul 120-752, Korea
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    • fax: 82-2-393-6884


  • Potential conflict of interest: Nothing to report.

Abstract

Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment-naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen–positive [HBeAg(+)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/mL (4.04-9.11 copies/mL), 3.58 IU/mL (1.17-5.10 IU/mL), and 1.71 Paul Ehrlich (PE) IU/mL (−0.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(+) patients, baseline alanine aminotransferase (P = 0.013), HBV DNA (P = 0.040), and qHBsAg levels (P = 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(+) group versus the SR(−) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(+) patients. Conclusion: Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on-treatment decline of qHBeAg in HBeAg(+) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated. (Hepatology 2011;)

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