title: Emerging pipeline drugs for hepatitis B infection.
abstract: BACKGROUND
  Chronic hepatitis B virus (HBV) infection continues to represent a global health concern with an estimated 350 - 400 million people infected worldwide. Current treatment options are either of two IFN-based therapies or either of five oral nucleos(t)ide analogs which are used as monotherapy or in combination. Control of viral replication can be achieved basically in all patients today. However, despite the clinical efficacy of antivirals, long-term management remains a clinical challenge mainly due to the slow kinetics of HBsAg clearance. Emergence of viral resistance has been a challenge in the past with some but not all oral therapies. The development of novel therapeutic agents with different mechanisms of action might provide new opportunities to clear HBsAg and achieve HBsAg seroconversion which could be maintained off therapy. The long-term efficacy of combinations of IFN and/or nucleos(t)ide analogs might achieve antiviral synergy, preventing drug resistance and clearing viral covalently close circular DNA and infected cells.
  
  
  METHODS
  This article provides a review of recent data on the safety and efficacy of existing and emerging agents for the treatment of chronic hepatitis B infection.
  
  
  CONCLUSIONS
  Currently, entecavir and tenofovir offer a safe and effective treatment option for patients with chronic HBV with minimal to no resistance. Although entecavir and tenofovir are able to suppress replication in essentially all patients, achieving HBsAg seroconversion remains suboptimal among all antiviral therapy. There are a number of new therapies in the pipeline for the treatment of chronic HBV infection as well as revisiting IFN combined or sequential to antiviral therapy.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Natravis
authors.initials: N
authors.lastname: Cox
authors.forename: Hans
authors.initials: H
authors.lastname: Tillmann
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015195:Drug Design; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006511:Hepatitis B Antigens / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D015507:Drugs, Investigational; D006511:Hepatitis B Antigens; D017325:Hepatitis B Vaccines; D063065:Organophosphonates; C413685:entecavir; D006147:Guanine; D000068698:Tenofovir; D000225:Adenine