HBeAg-negative chronic hepatitis B: why do I treat my patients with pegylated interferon-alfa?

Liver Int. 2014 Feb;34 Suppl 1:127-32. doi: 10.1111/liv.12404.


HBeAg-negative chronic hepatitis B (CHB) is the most frequent and aggressive type of CHB. The current therapeutic options for CHB include pegylated-interferon-alfa (PEG-IFNα) and nucleos(t)ide analogues (NAs). NAs are well-tolerated and safe agents that effectively inhibit viral replication, but they should be given as long-term, probably lifelong therapy, in particular in HBeAg-negative CHB. Thus, the finite, usually 48-week, duration is the main advantage of PEG-IFNα, providing sustained virological responses (SVR) off-therapy in approximately one-fourth of patients with HBeAg-negative CHB and often leading to HBsAg loss. However, the limited efficacy is the main factor restricting the use of PEG-IFNα in CHB and therefore identifying the predictors of response is of great clinical importance. No reliable baseline predictors of response to PEG-IFNα have been identified to date, but certain studies have identified satisfactory predictors of post-PEG-IFNα response using on-treatment serological markers, mostly HBsAg levels. In particular, in HBeAg-negative CHB patients mostly with genotype D a lack of decline in HBsAg levels and a lack of decrease in HBV DNA levels ≥2 log10 copies/ml at week-12 has a nearly 100% negative predictive value for SVR off-treatment and is now recommended as a stopping rule for early discontinuation of ineffective PEG-IFNα. Prolonging PEG-IFNα therapy to 96 weeks seems to provide higher SVR rates but the application and efficacy of this approach requires further study. The combination of PEG-IFNα with NAs, mostly lamivudine, has not resulted in any therapeutic benefit so far, but newer combined approaches with PEG-IFNα and NA(s) are currently under study.

Keywords: HBV DNA; HBsAg; adefovir; combination; hepatitis B; interferon; lamivudine; nucleos(t)ide analogue.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • DNA, Viral / analysis
  • Drug Therapy, Combination / methods*
  • Drug Therapy, Combination / trends
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Nucleosides / therapeutic use
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Time Factors
  • Treatment Outcome


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