title: Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B.
abstract: BACKGROUND
  Nucleos(t)ides effectively halt disease progression in hepatitis B but require long-term medication.
  
  
  OBJECTIVE
  To determine whether add-on of peg-IFN to an ongoing nucleos(t)ide therapy accelerates decline of HBsAg and induces seroconversion.
  
  
  METHODS
  We observed HBsAg kinetics in 12 patients on a stable oral therapy with undetectable HBV-DNA who additionally received peg-IFN-alfa 2a as an individualized therapy. 3 patients were HBeAg positive. Mean baseline HBsAg was 4695 (range 16-15,120)IU/ml.
  
  
  RESULTS
  A continuous decline of HBsAg was observed in 2 patients. The slope, respectively, became detectable at week 8 or 16. HBsAg had dropped by 2.90log(10) or 4.25log(10) fold at week 48, and anti-HBs appeared at week 40 or 32. Patient A - HBe-positive, genotype A, F3 fibrosis - had been HBV-DNA negative for 10 months receiving entecavir plus tenofovir. Previous therapy with peg-IFN had been unsuccessful, but now the patient experienced HBeAg seroconversion at week 24. Patient B - HBeAg negative, genotype D, cirrhosis - had a low initial HBsAg level of 16U/l. Receiving entecavir, his HBV-DNA had previously been non-detectable for 27 months. In the remaining 10 patients HBsAg declined only by a mean of 0.09log(10) (range 0.01-0.25log(10)) after 8-24 (mean 16.4) weeks, and therefore, peg-IFN was stopped. No unexpected side effects were observed.
  
  
  CONCLUSIONS
  We observed that the add-on of peg-IFN induced HBsAg seroconversion in 2 out of 12 patients. Response rates may have been higher with prolongation of therapy. The add-on concept merits to be evaluated in a clinical trial.
authors.affiliation: I. Medical Department, University Hospital Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Jens.kittner@unimedizin-mainz.de
authors.forename: Jens M
authors.initials: JM
authors.lastname: Kittner
authors.forename: Martin F
authors.initials: MF
authors.lastname: Sprinzl
authors.forename: Annette
authors.initials: A
authors.lastname: Grambihler
authors.forename: Arndt
authors.initials: A
authors.lastname: Weinmann
authors.forename: Jörn M
authors.initials: JM
authors.lastname: Schattenberg
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Marcus
authors.initials: M
authors.lastname: Schuchmann
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a