title: HBeAg-negative chronic hepatitis B: why do I treat my patients with pegylated interferon-alfa?
abstract: 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.
authors.affiliation: Academic Department of Gastroenterology, Athens University Medical School, Laiko General Hospital, Athens, Greece.
authors.forename: Jiannis
authors.initials: J
authors.lastname: Vlachogiannakos
authors.forename: George V
authors.initials: GV
authors.lastname: Papatheodoridis
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000032:analysis; D004359:Drug Therapy, Combination / Q000379:methods* / Q000639:trends; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D009705:Nucleosides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D009705:Nucleosides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a
keywords: HBV DNA; HBsAg; adefovir; combination; hepatitis B; interferon; lamivudine; nucleos(t)ide analogue