New perspectives in the therapy of chronic hepatitis B

Since approval of the first nucleos(t)ide analogue (NUC) in 1998, remarkable advances have been made in antiviral treatment of chronic hepatitis B virus (HBV) infection. Both interferon-based therapy and treatment with NUCs have evolved to the stage that pegylated interferon (Peg-IFN) has replaced conventional IFN, and entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have become the first-line oral treatments.1–3 As the therapeutic outcomes are still far from satisfactory, many attempts have been made to optimise antiviral therapy of chronic HBV infection. Along with the evolution of drug therapy, quantitation of hepatitis B surface antigen (HBsAg) has gained popularity as a clinically useful seromarker for assessing the natural course and response to therapy of chronic HBV infection. In addition, the discovery of IL28B polymorphism, which has shed new light on the treatment of hepatic C virus (HCV) infection, has been applied in the study of the response of patients with HBV to IFN regimens. These recent developments are reviewed in this article, focusing on the following topics: IL28B and response to IFN or Peg-IFN therapy; response-guided therapy of Peg-IFN treatment; ETV and TDF in field practice naive patients. ### IL28B as a baseline host factor in the response to IFN- or Peg-IFN-based therapy Peg-IFN treatment remains an attractive anti-HBV strategy because it provides higher rates of off-therapy immune control (normal alanine aminotransferase (ALT) levels coupled with HBV DNA <2000 IU/ml and anti-HBe positivity) compared with NUCs.1–3 These benefits, however, are restricted to a subgroup of patients, ∼30%, and the tolerability, although significantly improved compared with standard IFN, is suboptimal, and also there are significant costs. There have been many attempts to identify pretreatment predictors of a response, resulting in the identification of high ALT levels, low HBV DNA, and virus genotype as significant predictors.1–3 However, these factors have limited applicability in clinical practice, the most important …