Gastroenterology

Gastroenterology

Volume 135, Issue 2, August 2008, Pages 459-467
Gastroenterology

Clinical–Liver, Pancreas, and Biliary Tract
Sustained HBeAg and HBsAg Loss After Long-term Follow-up of HBeAg-Positive Patients Treated With Peginterferon α-2b

https://doi.org/10.1053/j.gastro.2008.05.031Get rights and content

Background & Aims: The aim of this study was to evaluate the long-term sustainability of response in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B treated with pegylated interferon (PEG-IFN) α-2b alone or in combination with lamivudine. Methods: All 266 patients enrolled in the HBV99-01 study were offered participation in a long-term follow-up (LTFU) study. Patients were treated with PEG-IFN α-2b (100 μg/wk) alone or in combination with lamivudine (100 mg/day) for 52 weeks. Initial response was defined as HBeAg negativity at 26 weeks posttreatment. For the LTFU study, patients had one additional visit after the initial study (mean interval, 3.0 ± 0.8 years). Results: Of 266 patients enrolled in the initial study, 172 (65%) participated in the LTFU study. At LTFU, HBeAg and hepatitis B surface antigen (HBsAg) negativity were observed in 37% and 11% of 172 patients, respectively. Sixty-four patients were classified as initial responders and 108 as nonresponders. Among the initial responders, sustained HBeAg negativity and HBsAg loss were observed in 81% and 30%, respectively. Significantly higher rates of HBeAg negativity were observed in genotype A–infected initial responders compared with those with genotype non-A (96% vs 76%; P = .06) as well as HBsAg loss (58% vs 11%; P < .001). Conclusions: HBeAg loss after treatment with PEG-IFN α-2b alone or in combination with lamivudine is sustained in the majority of patients and is associated with a high likelihood of HBsAg loss, particularly in genotype A–infected patients. Therefore, PEG-IFN α-2b remains an important treatment option in this era of nucleos(t)ide analogue therapy.

Section snippets

Participants

All 266 patients enrolled in the HBV99-01 study (42 centers in 15 countries) were eligible for inclusion in this long-term follow-up (LTFU) study.7 Patients were treated with PEG-IFN α-2b 100 μg weekly (PegIntron; Schering-Plough, Kenilworth, NJ) in combination with placebo or lamivudine 100 mg daily (Zeffix; GlaxoSmithKline, Greenford, England) for 52 weeks. After 32 weeks, the dosage of PEG-IFN α-2b was lowered to 50 μg/wk to prevent early discontinuation of therapy due to side effects.7 The

Patients

Of 266 patients from 41 centers participating in the HBV99-01 study, 172 patients (65%) from 28 centers (68%) were enrolled in the LTFU study. The LTFU study overview is shown in Figure 1. Patients were followed up for a mean of 3.0 ± 0.8 years (range, 1.6–5.0 years) after the end of the initial study. The majority of the 94 patients who were not enrolled in the LTFU study did not participate because the local study site did not, for variable reasons, take part in this study (n = 52; 55%) or

Discussion

This is the first study documenting long-term outcome after treatment with PEG-IFN α-2b alone or in combination with lamivudine in patients with chronic hepatitis B. We found that 81% of patients with loss of HBeAg at 26 weeks posttreatment remained HBeAg negative after a mean of 3 years. About two thirds of sustained HBeAg responders maintained an HBV DNA level <10,000 copies/mL and a normal ALT level, reflecting inactive disease. An increase in HBsAg negativity was observed in the LTFU study,

References (30)

  • V. Carreno et al.

    Long-term follow-up of hepatitis B chronic carriers who responded to interferon therapy

    J Hepatol

    (1992)
  • A.S. Lok et al.

    Long-term follow-up of chronic hepatitis B patients treated with interferon alfa

    Gastroenterology

    (1993)
  • P. Marcellin et al.

    The majority of patients with HBeAg-negative chronic hepatitis B treated with peginterferon alfa-2a (40KD) [Pegasys®] sustain responses 2 years post-treatment

    J Hepatol

    (2006)
  • D. Lavanchy

    Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures

    J Viral Hepat

    (2004)
  • W.M. Lee

    Hepatitis B virus infection

    N Engl J Med

    (1997)

    • Cited by (0)

    Organized and sponsored by the Foundation for Liver Research (SLO) (Rotterdam, The Netherlands) and supported by Schering-Plough International (Kenilworth, NJ).

    E.H.C.J.B. has received speaker's honoraria from Novartis and Roche. S.V.F. has served as a consultant for Hoffman-La Roche and Schering-Plough and has received research support from Schering-Plough. H.L.A.J. has served as a consultant for Bristol-Myers Squibb, Gilead, Novartis, and Roche and has received research support from Bristol-Myers Squibb, Novartis, Roche, and Schering-Plough. The following authors have nothing to disclose: H.J.F., Y.C., K.S., J.T., F.T., T.M.K.S., T.M., U.S.A., M.S., W.T., A.J.V., and B.E.H. Potential investigator conflicts of interest have not been disclosed to study participants.

    Members of the HBV99-01 LTFU study group include the following: Belgium: F. Nevens, E. de Wit (University Hospital Gasthuisberg, Leuven); P. P. Michielsen, R. Braspenning (University Hospital, Antwerp); H. van Vlierberghe, A. de Geyter (University Hospital, Gent). Canada: E. J. Heathcote, D. Kaznowski (Toronto Western Hospital University Health Network, Toronto); S. Bojarski (Liver Disease Unit, Mount Sinai Hospital, Toronto). Denmark: L. R. Mathiesen, G. Kronborg, L. Rosenørn (Copenhagen University Hospital, Hvidovre). Germany: G. Gerken, S. Bein (University Hospital, Essen). Greece: G. Kitis (George Papanikolaou General Regional Hospital, Thessaloniki). Italy: G. B. Gaeta (Ospedale Gesù e Maria, Napoli); F. D'Antona, G. Montalto (Università di Palermo, Palermo). Malaysia: S. Sharmila (Hospital Selayang, Institute for Medical Research, Kuala Lumpur). The Netherlands: E. Verhey, G. Ramdjan, L. A. van Santen, A. Heijens, M. Ouwendijk, J. Francke, S. Diepstraten-Pas (Erasmus MC University Medical Center, Rotterdam); C. M. J. van Nieuwkerk, C. van Doorn (VU University Medical Center, Amsterdam); J. Drenth (University Medical Centre Radboud, Nijmegen); J. W. den Ouden-Muller (St Franciscus Hospital, Rotterdam); R. A. de Vries, P. van Embden (Rijnstate Hospital, Arnhem). Poland: R. Flisiak (Medical University of Białystok, Białystok). Singapore: R. Guan (Mount Elizabeth Medical Center, Singapore). Spain: M. Buti (Hospital General Universitari Pall d'Hebron, Barcelona); M. Rodriguez (Hospital Central de Asturias, Oviedo). Turkey: H. Simsek (Hacettepe University Faculty of Medicine, Ankara).

    View full text
    Copyright © 2008 AGA Institute. Published by Elsevier Inc. All rights reserved.