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Br Med Bull. 2015 Sep 15. pii: ldv039. [Epub ahead of print]
New paradigms in hepatitis B management: only diamonds are forever.Coffin CS1, Lee SS2.
Author information
- 1Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada [email protected].
- 2Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada.
AbstractINTRODUCTION: 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'.
© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].
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