Serum HBV RNA as a Predictor of Peginterferon Alfa-2a Response in Patients With HBeAg-Positive Chronic Hepatitis B

J Infect Dis. 2018 Aug 24;218(7):1066-1074. doi: 10.1093/infdis/jiy270.

Abstract

Background: Hepatitis B virus (HBV) RNA is a novel serum biomarker that has the potential to predict treatment response in patients with chronic hepatitis B. We explored whether HBV RNA serum levels can predict hepatitis B e antigen (HBeAg) seroconversion in patients treated with peginterferon alfa-2a.

Methods: Serum samples from HBeAg-positive patients previously treated with peginterferon alfa-2a in 2 large randomized controlled trials were retrospectively analyzed. HBV RNA levels were measured using a real-time polymerase chain reaction assay. Ability of individual biomarkers to predict HBeAg seroconversion at 24 weeks posttreatment was evaluated using receiver operating characteristics (ROC) analyses.

Results: The study included 131 subjects (70% male, 96% Asians, 35% HBV genotypes B, and 61% C), 76 treated with peginterferon alfa-2a alone and 55 in combination with lamivudine. Median HBV RNA levels were significantly lower, at all timepoints, in patients achieving HBeAg seroconversion. Levels of HBV RNA at treatment weeks 12 and 24 showed good ability to predict HBeAg seroconversion (area under ROC scores >0.75, P < .001). A HBV RNA cutoff of >5.5 log10 copies/mL identified 30% of nonresponders at week 12 (negative predictive value >90%).

Conclusion: Serum HBV RNA is an early predictor of HBeAg seroconversion in patients treated with peginterferon alfa-2a.

Clinical trials registration: NCT01705704.

Publication types

  • Clinical Trial, Phase III
  • Clinical Trial, Phase IV
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Biomarkers / analysis
  • Female
  • Hepatitis B e Antigens / blood*
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Male
  • Polyethylene Glycols / therapeutic use*
  • RNA, Viral / blood
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Seroconversion
  • Young Adult

Substances

  • Antiviral Agents
  • Biomarkers
  • Hepatitis B e Antigens
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • peginterferon alfa-2a

Associated data

  • ClinicalTrials.gov/NCT01705704