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Quantitation of large, middle and small hepatitis B surface proteins in HBeAg-positive patients treated with peginterferon alfa-2a.

  • Rinker, Franziska1, 2
  • Bremer, Corinna M3, 4
  • Schröder, Kathrin3, 4
  • Wiegand, Steffen B1
  • Bremer, Birgit1
  • Manns, Michael P1, 2
  • Kraft, Anke R1, 2
  • Wedemeyer, Heiner1, 2
  • Yang, Lei5
  • Pavlovic, Vedran6, 7
  • Wat, Cynthia6
  • Gerlich, Wolfram H3
  • Glebe, Dieter3, 4
  • Cornberg, Markus1, 2, 8, 9
  • 1 Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625, Hannover, Germany. , (Germany)
  • 2 German Center for Infection Research (DZIF), Partner Site: Hannover, Braunschweig, Germany. , (Germany)
  • 3 Institute of Medical Virology, Justus Liebig University Giessen, National Reference Center for Hepatitis, B and D Viruses, D-35392, Giessen, Germany. , (Germany)
  • 4 German Center for Infection Research (DZIF), Partner Site: Giessen-Marburg-Langen, Germany. , (Germany)
  • 5 Roche (China) Holding Ltd, Product Development - Biometrics/Biostatistics, Shanghai, 201203, China. , (China)
  • 6 Roche Products Ltd, Product Development - Clinical Science, Welwyn Garden City, AL7 1TW, UK.
  • 7 VP Pharma Consultancy, London, UK.
  • 8 Centre for Individualized Infection Medicine (CIIM), Hannover, Germany. , (Germany)
  • 9 Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany. , (Germany)
Published Article
Liver international : official journal of the International Association for the Study of the Liver
Publication Date
Nov 13, 2019
DOI: 10.1111/liv.14298
PMID: 31721419


Hepatitis B virus (HBV) contains three viral surface proteins, large, middle and small hepatitis B surface protein (LHBs, MHBs, SHBs). Proportions of LHBs and MHBs are lower in patients with inactive versus active chronic infection. Interferon alfa may convert HBeAg-positive chronic hepatitis B (CHB) to an inactive carrier state, but prediction of sustained response is unsatisfactory. The aim of this study was to test the hypothesis that quantification of MHBs and LHBs may allow for a better prognosis of therapeutic response than total hepatitis B surface antigen (HBsAg) concentration. HBs proteins were measured before and during peginterferon alfa-2a therapy in serum from 127 Asian patients with HBeAg-positive CHB. Sustained response was defined as hepatitis B e antigen (HBeAg) seroconversion 24 weeks post-treatment. Mean total HBs levels were significantly lower in responders versus nonresponders at all time points (P<.05) and decreased steadily during the initial 24 weeks' treatment (by 1.16 versus 0.86 ng/mL in responders/nonresponders, respectively) with unchanged relative proportions. Genotype B had a twofold higher proportion of LHBs than genotype C (13% versus 6%). HBV DNA, HBeAg, HBsAg, and HBs protein levels predicted response equally well but not optimally (area under the ROC curve values >0.70). HBs proteins levels differ by HBV genotype. However, quantification of HBs proteins has no advantage over the already established HBsAg assays to predict response to peginterferon alfa-2a therapy in HBeAg-positive patients. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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