title: New paradigms in hepatitis B management: only diamonds are forever.
abstract: BACKGROUND
  The hepatitis B virus (HBV) causes chronic hepatitis B (CHB) in ∼350 million people worldwide who have an increased risk of end-stage liver disease and/or hepatocellular carcinoma.
  
  
  METHODS
  Several peer-reviewed papers featuring new approaches to anti-HBV management. Additionally, we also reviewed recent abstract presentations at international congresses.
  
  
  RESULTS
  There has been great progress in CHB therapy with the development of standard and pegylated interferon (i.e. PEG-IFN) as well as nucleos/tide analogs (NAs). IFN has both antiviral and immunomodulatory effects and through immune-mediated destruction of infected hepatocytes offers the possibility of finite therapy. However, this 'killing for a cure' antiviral strategy may not be tolerated in many, especially in cirrhotic patients. NAs inhibit viral reverse transcriptase, have few side effects and prevent liver disease progression, but cannot offer a cure as they have little effect on the resilient HBV covalently closed circular DNA (cccDNA) intermediate. Moreover, NAs such as tenofovir and entecavir offer a high genetic barrier to resistance, but are expensive and not readily available in many global regions.
  
  
  CONCLUSIONS
  Despite significant treatment advances, there is increased recognition of the need for improved anti-HBV treatments, and new virologic tests for monitoring treatment response.
  
  
  RESULTS
  The role of quantitative hepatitis B surface antigen, intrahepatic cccDNA levels and viral genotype in selecting treatment candidates and refining NA stopping rules.
  Potential new therapies include viral entry inhibitors, RNA interference technologies (i.e. RNAi) and small molecules that modulate cccDNA transcription, as well as novel immunomodulatory therapies to boost HBV-specific T cell responses. The ultimate goal of new tests and anti-HBV therapies is to reduce the burden and expense of life-long CHB treatment, as 'only diamonds are forever'.
authors.affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada cscoffin@ucalgary.ca.
authors.forename: Carla S
authors.initials: CS
authors.lastname: Coffin
authors.affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Lee
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016903:Drug Monitoring / Q000379:methods; D006514:Hepatitis B Surface Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000627:therapeutic use; D055666:Lipopeptides / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D051193:Toll-Like Receptors / Q000819:agonists; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006514:Hepatitis B Surface Antigens; D007155:Immunologic Factors; D007372:Interferons; D007378:Interleukins; D055666:Lipopeptides; D051193:Toll-Like Receptors; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C571888:myrcludex-B
keywords: HBV cccDNA; chronic hepatitis B; cure; immune therapy; nucleos/tide analog; quantitative HBV surface antigen