Anti-E1E2 antibodies status prior therapy favors direct-acting antiviral treatment efficacy

Clin Res Hepatol Gastroenterol. 2018 Sep;42(4):313-318. doi: 10.1016/j.clinre.2018.02.002. Epub 2018 Mar 16.

Abstract

Introduction: Presence of anti-E1E2 antibodies was previously associated with spontaneous cure of hepatitis C virus (HCV) and predictive before treatment of a sustained virological response (SVR) to bi- or tri-therapy in naïve or experienced patients, regardless of HCV genotype. We investigated the impact of anti-E1E2 seroprevalence at baseline on treatment response in patients receiving direct-acting antiviral (DAA) therapy.

Material and methods: We screened anti-E1E2 antibodies by ELISA in serum samples collected at treatment initiation for two groups of patients: 59 with SVR at the end of DAA treatment and 44 relapsers after DAA treatment. Nineteen patients received a combination of ribavirin (RBV) or PEG-interferon/ribavirin with sofosbuvir or daclatasvir and others received interferon-free treatment with DAA±RBV. HCV viral load was measured at different time points during treatment in a subgroup of patients.

Results: A significant association was observed between presence of anti-E1E2 and HCV viral load<6log10 prior treatment. Among patients with anti-E1E2 at baseline, 70% achieved SVR whereas among patients without anti-E1E2, only 45% achieved SVR. Conversely, 66% of patients experiencing DAA-failure were anti-E1E2 negative at baseline. In the multivariate analysis, presence of anti-E1E2 was significantly associated with SVR after adjustment on potential cofounders such as age, sex, fibrosis stage, prior HCV treatment and alanine aminotransferase (ALT) level.

Conclusions: The presence of anti-E1E2 at treatment initiation is a predictive factor of SVR among patients treated with DAA and more likely among patients with low initial HCV viral load (<6log10). Absence of anti-E1E2 at baseline could predict DAA-treatment failure.

Keywords: Direct-acting antivirals; E1E2 envelope; Hepatitis C; Neutralizing antibodies; Relapse; Sustained virological response.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies / blood*
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Carbamates
  • Drug Therapy, Combination
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Imidazoles / therapeutic use
  • Interferon-alpha / therapeutic use
  • Male
  • Middle Aged
  • Peptides / immunology*
  • Polyethylene Glycols / therapeutic use
  • Pyrrolidines
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Ribavirin / therapeutic use
  • Seroepidemiologic Studies
  • Sofosbuvir / therapeutic use
  • Valine / analogs & derivatives
  • Viral Load / drug effects

Substances

  • Antibodies
  • Antiviral Agents
  • Biomarkers
  • Carbamates
  • E1E2 peptide
  • Imidazoles
  • Interferon-alpha
  • Peptides
  • Pyrrolidines
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Valine
  • daclatasvir
  • peginterferon alfa-2a
  • Sofosbuvir