title: Optimal therapy for chronic hepatitis B: hepatitis B virus combination therapy?
abstract: Currently available antiviral treatment for chronic hepatitis B can be divided into two classes of therapeutic agents: pegylated interferon alpha (PEG-IFN) and nucleos(t)ide analogues (NAs). The major advantages of NAs are good tolerance and potent antiviral activity associated with high rates of on-treatment response to therapy. The advantages of PEG-IFN include a finite course of treatment, the absence of drug resistance, and an opportunity to obtain a durable post-treatment response to therapy. The use of these two antiviral agents with different mechanisms of action in combination is theoretically an attractive approach for treatment, either simultaneously, as sequential combination therapy (add-on), or even as an immediate switch from one agent to the other. Different NAs have also been combined in certain clinical situations. At present, several studies have confirmed certain virological advantages to combination therapies, but pivotal prospective studies demonstrating long-term clinical benefit to patients are still missing. Therefore, combination treatment, especially with PEG-IFN plus NAs, is not indicated and was not recommended by the European Association for the Study of the Liver Clinical Practice Guidelines written in 2012, while the guidelines for the use of combination NAs is limited to very few clinical situations.
authors.affiliation: IFI Institute at the Asklepios Klinik St Georg Hamburg, University of Hamburg, Hamburg, Germany.
authors.forename: Jorg
authors.initials: J
authors.lastname: Petersen
authors.forename: Maura
authors.initials: M
authors.lastname: Dandri
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D004270:DNA, Circular / Q000235:genetics; D004359:Drug Therapy, Combination / Q000379:methods* / Q000639:trends; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D014158:Transcription, Genetic / Q000235:genetics; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004270:DNA, Circular; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C413685:entecavir; D006147:Guanine; C100416:peginterferon alfa-2a
keywords: HBsAg; HBsAg loss; NUC; PEGIFN; cccDNA; combination therapy