New paradigms in hepatitis B management: only diamonds are forever.

INTRODUCTION 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. SOURCES OF DATA Several peer-reviewed papers featuring new approaches to anti-HBV management. Additionally, we also reviewed recent abstract presentations at international congresses. AREAS OF AGREEMENT 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. GROWING POINTS Despite significant treatment advances, there is increased recognition of the need for improved anti-HBV treatments, and new virologic tests for monitoring treatment response. AREAS OF CONTROVERSY The role of quantitative hepatitis B surface antigen, intrahepatic cccDNA levels and viral genotype in selecting treatment candidates and refining NA stopping rules. AREAS TIMELY FOR DEVELOPING NEW RESEARCH 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'.