Hepatitis B core-related antigen levels are associated with response to entecavir and peginterferon add-on therapy in hepatitis B e antigen–positive chronic hepatitis B patients  M.J.H. van Campenhout, W.P. Brouwer, G.W. van Oord, Q. Xie, Q. Zhang, N. Zhang, S. Guo, F. Tabak, A. Streinu-Cercel, J. Wang, S.D. Pas, M.J. Sonneveld, R.J. de Knegt, A. Boonstra, B.E. Hansen, H.L.A. Janssen  Clinical Microbiology and Infection  Volume 22, Issue 6, Pages 571.e5-571.e9 (June 2016) DOI: 10.1016/j.cmi.2016.02.002 Copyright © 2016 Terms and Conditions

Fig. 1 Decline in HBcrAg and HBsAg between week 0 and 72 according to week 72 CR and HBsAg response. Four upper panels display decline in HBcrAg expressed as mean log U/mL; four lower panels display decline in qHBsAg, expressed as mean log IU/mL. Error bars represent standard error of mean. Declines are consecutively stratified according to week 72 CR and week 72 HBsAg response. (a) In ETV monotherapy arm, significantly greater decline was observed for patients with CR than those without CR (week 24: −2.19 vs. −1.04 log U/mL, p <0.001; week 72: −3.22 vs. −1.71 log U/mL, p <0.001). This was also observed from week 48 to week 72: −0.59 vs. −0.28 log U/mL, p = 0.05, respectively. In patients who experienced HBsAg response, mean declines in HBcrAg were also stronger than in patients without HBsAg response (week 24: −1.64 vs. −1.10 log U/mL, p = 0.03; week 72: −2.60 vs. −1.74 log U/mL, p <0.001). In the PEG-IFN add-on arm, decline in HBcrAg was stronger in patients who experienced CR than in those who did not (−3.16 vs. −1.83 log U/mL, p <0.001). Between week 48 (the moment of PEG-IFN cessation) and week 72, decline in HBcrAg in patients with CR was −0.49 log U/mL, whereas it was −0.15 log U/mL in those without CR (p = 0.04). Patients with HBsAg response at week 72 in add-on arm showed more decline in HBcrAg than those with no HBsAg response (−2.51 vs. −2.04 log U/mL, p = 0.05). Quantitative HBsAg levels also declined more strongly in patients with vs. without CR (ETV monotherapy: −0.58 vs. −0.16 log IU/mL, p <0.001), PEG-IFN add-on: −0.98 vs. −0.70 log IU/mL, p <0.001), and in patients with vs. without HBsAg response (ETV monotherapy: −1.13 vs. −0.08 log IU/mL, p <0.001; PEG-IFN add-on: −1.38 vs. −0.27 log IU/mL, p <0.001). (b) Individual HBcrAg dynamics in patients who stopped ETV at week 72. Twenty-two patients stopped ETV at week 72 because they experienced CR at week 48. Week 72 and 96 HBcrAg levels were available at both time points in 20 of 22 patients. Red lines represent patients whose CR was not maintained through week 96 (HBeAg seroreversion and/or HBV DNA >200 IU/mL after stopping ETV). CR, combined response; ETV, entecavir; HBcrAg, hepatitis B core-related antigen; HBsAg, hepatitis B surface antigen; PEG-IFN, peginterferon. Clinical Microbiology and Infection 2016 22, 571.e5-571.e9DOI: (10.1016/j.cmi.2016.02.002) Copyright © 2016 Terms and Conditions

Clinical Microbiology and Infection 2016 22, 571. e5-571. e9DOI: (10 Clinical Microbiology and Infection 2016 22, 571.e5-571.e9DOI: (10.1016/j.cmi.2016.02.002) Copyright © 2016 Terms and Conditions

Clinical Microbiology and Infection 2016 22, 571. e5-571. e9DOI: (10 Clinical Microbiology and Infection 2016 22, 571.e5-571.e9DOI: (10.1016/j.cmi.2016.02.002) Copyright © 2016 Terms and Conditions

Clinical Microbiology and Infection 2016 22, 571. e5-571. e9DOI: (10 Clinical Microbiology and Infection 2016 22, 571.e5-571.e9DOI: (10.1016/j.cmi.2016.02.002) Copyright © 2016 Terms and Conditions

Clinical Microbiology and Infection 2016 22, 571. e5-571. e9DOI: (10 Clinical Microbiology and Infection 2016 22, 571.e5-571.e9DOI: (10.1016/j.cmi.2016.02.002) Copyright © 2016 Terms and Conditions