title: Baseline HBsAg and HBcrAg titres allow peginterferon-based 'precision medicine' in HBeAg-negative chronic hepatitis B patients.
abstract: Quantitative hepatitis B core-related antigen (qHBcrAg) has been proposed as an additional marker to quantitative HBsAg (qHBsAg), for management of chronic hepatitis B. Evaluate baseline combination of qHBsAg and qHBcrAg for identification of patients that could benefit from pegylated interferon-alpha-2a (PegIFN)-based therapy. Sixty-two HBeAg-negative patients treated with PegIFN or PegIFN plus tenofovir disoproxil fumarate (PegIFN+TDF). HBsAg and HBcrAg titres were evaluated at baseline. Thirty patients received PegIFN and 32 PegIFN+TDF. SR was 10 of 30 and 17 of 32 in PegIFN and PegIFN+TDF patients, respectively. Cut-offs determined by maximized Youden's index for identifying patients likely to respond to therapy were as follows: 3.141 log10IU/mL and 3.450 log10U/mL for HBsAg and HBcrAg, respectively. At the end of 3 years post-treatment follow-up, HBsAg loss was observed in 7 of 30 and 6 of 32 in PegIFN and PegIFN+TDF patients, respectively. The AUC was estimated to be 0.716 (95% CI [0.578, 0.855]) for HBsAg and 0.668 (95% CI [0.524, 0.811]) for HBcrAg (P=.5541). PPVs for AUCs(95%CI) were 0.762(0.590-0.947), 0.714(0.533-1.000) and 0.800(0.611-1.000), and NPVs for AUCs(95%CI) were 0.756(0.660-0.899), 0.718(0.630-0.857) and 0.765(0.675-0.889) for qHBsAg, qHBcrAg and the combination of both markers, respectively. Baseline qHBsAg 3.141 log10IU/mL and qHBcrAg 3.450 log10U/mL thresholds used separately or in combination allow prediction of response, prior to PegIFN-based therapy, with a PPV of 80.3% and NPV of 76.5%. Baseline qHBsAg is predictive of HBsAg loss. Both markers could be used, separately or in combination, for PegIFN-based 'precision therapy'. Our results emphasize that the combination of PegIFN alpha-2a plus TDF with 53% of SR might be an alternative to finite therapy.
authors.affiliation: INSERM, UMR1149, Centre de Recherche sur l'Inflammation, Paris, France. michelle.martinot@inserm.fr.|Université Denis Diderot Paris 7, Paris, France. michelle.martinot@inserm.fr.
authors.forename: M
authors.initials: M
authors.lastname: Martinot-Peignoux
authors.affiliation: INSERM, UMR1149, Centre de Recherche sur l'Inflammation, Paris, France.|Université Denis Diderot Paris 7, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Lapalus
authors.affiliation: Service de Microbiolgie Pole B2P, Hôpital saint Louis, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Maylin
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon AP-HP, Clichy Cedex, France.
authors.forename: N
authors.initials: N
authors.lastname: Boyer
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon AP-HP, Clichy Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Castelnau
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon AP-HP, Clichy Cedex, France.
authors.forename: N
authors.initials: N
authors.lastname: Giuily
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon AP-HP, Clichy Cedex, France.
authors.forename: M
authors.initials: M
authors.lastname: Pouteau
authors.affiliation: INSERM, UMR1149, Centre de Recherche sur l'Inflammation, Paris, France.|Université Denis Diderot Paris 7, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Moucari
authors.affiliation: INSERM, UMR1149, Centre de Recherche sur l'Inflammation, Paris, France.|Université Denis Diderot Paris 7, Paris, France.|Service de Microbiolgie Pole B2P, Hôpital saint Louis, Paris, France.|Service d'Hépatologie, Hôpital Beaujon AP-HP, Clichy Cedex, France.
authors.forename: T
authors.initials: T
authors.lastname: Asselah
authors.affiliation: INSERM, UMR1149, Centre de Recherche sur l'Inflammation, Paris, France.|Université Denis Diderot Paris 7, Paris, France.|Service de Microbiolgie Pole B2P, Hôpital saint Louis, Paris, France.|Service d'Hépatologie, Hôpital Beaujon AP-HP, Clichy Cedex, France.
authors.forename: P
authors.initials: P
authors.lastname: Marcellin
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006512:Hepatitis B Core Antigens / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D057285:Precision Medicine / Q000379:methods*; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D000072230:Sustained Virologic Response; D000068698:Tenofovir / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000068698:Tenofovir; C100416:peginterferon alfa-2a
keywords: HBV; nucleos(t)ide analogues; pegylated interferon-alpha-2a; prognosis; serum markers