title: Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa-2a combination therapy for chronic hepatitis B.
abstract: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy.
  
  
  
  To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks.
  
  
  
  A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 μg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72.
  
  
  
  Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72.
  
  
  
  HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.
authors.affiliation: Paris, France.
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authors.initials: P
authors.lastname: Marcellin
authors.affiliation: Seoul, South Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Kaohsiung, Taiwan.
authors.forename: W-L
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: Hong Kong, China.
authors.forename: A J
authors.initials: AJ
authors.lastname: Hui
authors.affiliation: Istanbul, Turkey.
authors.forename: F
authors.initials: F
authors.lastname: Tabak
authors.affiliation: Surat, India.
authors.forename: R
authors.initials: R
authors.lastname: Mehta
authors.affiliation: Hamburg, Germany.
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authors.lastname: Petersen
authors.affiliation: Kaohsiung, Taiwan.
authors.forename: C-M
authors.initials: CM
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authors.affiliation: Philadelphia, USA.
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authors.affiliation: Toronto, ON, Canada.
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authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
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authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
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authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Martins
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
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authors.lastname: Charuworn
authors.affiliation: Gilead Sciences, Inc., Foster City, CA, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Yee
authors.affiliation: Singapore.
authors.forename: S G
authors.initials: SG
authors.lastname: Lim
authors.affiliation: London, UK.
authors.forename: G R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Fung
authors.affiliation: Pontevedra, Spain.
authors.forename: L
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authors.lastname: Morano
authors.affiliation: Villejuif, France.
authors.forename: D
authors.initials: D
authors.lastname: Samuel
authors.affiliation: London, UK.
authors.forename: K
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authors.lastname: Agarwal
authors.affiliation: Ankara, Turkey.
authors.forename: R
authors.initials: R
authors.lastname: Idilman
authors.affiliation: Sydney, Australia.
authors.forename: S I
authors.initials: SI
authors.lastname: Strasser
authors.affiliation: Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Buti
authors.affiliation: Naples, Italy.
authors.forename: G B
authors.initials: GB
authors.lastname: Gaeta
authors.affiliation: Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Papatheodoridis
authors.affiliation: Bialystok, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Flisiak
authors.affiliation: Hong Kong, China. hlychan@cuhk.edu.hk.
authors.forename: H L Y
authors.initials: HL
authors.lastname: Chan
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000008:administration & dosage; D000068698:Tenofovir / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000068698:Tenofovir; C100416:peginterferon alfa-2a