icon-folder.gif   Conference Reports for NATAP  
  EASL 47th Annual Meeting
April 18th - 22nd 2012
Barcelona, Spain
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Relationship between precore / core promoter mutants, HBeAg levels and serological response in HBeAg-positive chronic hepatitis B treated with nucleos(t)ide analogues
  EASL 2012

Speaker: Roeland Zoutendijk Author: R. Zoutendijk1*, M. Sonneveld2, J. Reijnders2, A. van Vuuren2, S. Pas1, B. Hansen1, A. Boonstra2, H. Janssen2 Affiliation: 1Erasmus MC, 2Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. *r.zoutendijk@erasmusmc.nl

Background: Precore (PC) and core promoter (BCP) mutations are the most prevalent naturally occurring variations of hepatitis B virus (HBV) and are thought to reduce the production of HBeAg. Moreover, patients with these mutations remain viraemic despite HBeAg seroconversion and are at risk for developing liver related complications.

Methods: We investigated the influence PC/BCP mutants and their relation with HBeAg levels and HBeAg seroconversion in 138 HBeAg-positive patients treated with different nucleos(t)ide analogues. The presence of mutants was assessed at baseline by line probe assay (Innogenetics, Ghent, Belgium), HBeAg levels were measured by Elecsys (Roche). Median duration of therapy was 29 (IQR 18-56) months.

Results: Patients were predominantly male (78%) and harbored genotypes A (33%), B (18%), C (16%), D (27%) or other (5%). Patients were treated with lamivudine (LAM, 38%), adefovir (ADV, 22%), entecavir (30%), tenofovir (TDF, 6%) and TDF/ADV-LAM (4%). Fifty-three (38%) patients had wildtype (WT) virus at baseline, 25 (18%) PC, 33 (24%) BCP and 27 (20%) had both PC and BCP mutants. Baseline HBeAg levels were different within these 4 groups: 2.68 (WT), 1.77 (PC), 1.81 (BCP) and 1.48 (both mutants) log U/mL respectively (p< 0.001) and HBeAg levels correlated with HBV DNA (r=0.55; p< 0.001). HBeAg-seroconversion was achieved in 45 (33%) patients and HBsAg-seroconversion in 6 (4%) patients. In multivariate analysis, the presence of PC and/or BCP mutants (HR 2.30, p= 0.045), baseline HBV DNA (HR 0.82, p=0.08) and ALT (HR 1.04, p=0.02), but not HBeAg levels (p=0.36) were independently associated with HBeAg seroconversion. Patients with PC mutants had a much lower probability of achieving HBV DNA < 2000 IU despite HBeAg-seroconversion compared to patients without PC mutants (68% versus 100%, p=0.003). Confirmed HBeAg relapse was more frequently noted in patients with BCP mutations (46% versus 19%, p=0.06).

Presence of PC/BCP mutants before NUC therapy was associated with lower levels of HBeAg and a higher probability of HBeAg seroconversion. However, presence of PC/BCP mutants also predisposed to persistent replication or HBeAg relapse after HBeAg seroconversion.