Semin Liver Dis 2013; 33(02): 095-096
DOI: 10.1055/s-0033-1345712
Foreword
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Current Perspectives on Chronic Hepatitis B

Stephen Locarnini
1   Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia
,
Alex Thompson
1   Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia
2   Department of Gastroenterology, St Vincent's Hospital, Fitzroy, Victoria, Australia
› Author Affiliations
Further Information

Publication History

Publication Date:
08 June 2013 (online)

Since the last Seminars in Liver Disease special issue devoted to hepatitis B in 2006, two doyens of the field have passed away: Professor Barry Blumberg on April 5, 2011 and Professor R. Palmer Beasley on August 25, 2012. Both made enormous contributions to human health. By discovering and then successfully implementing the world's first anticancer vaccine, they helped many millions of people around the world enjoy a life free from the sequelae of chronic hepatitis B virus (HBV) infection. The editors wish to dedicate this special issue to Professor Blumberg and Professor Beasley.

Recently, there has been significant global as well as regional focus on viral hepatitis. In May 2010, the 63rd World Health Assembly passed a unanimous resolution proposed by the World Hepatitis Alliance (WHA) that included the establishment of World Hepatitis Day on July 28 (Professor Blumberg's birthday). This resolution also led to the establishment of a dedicated program at the WHO: The Global Hepatitis Program (GHP). The program comprises four interconnected axes: Axis 1—raising awareness, promoting partnership, and resourcing; Axis 2—evidence-based policy and data for action; Axis 3—prevention of transmission; and Axis 4—screening, care, and treatment.[1] This special issue of Seminars in Liver Disease is focused on Axes 2, 3, and 4 of the WHO GHP, and is very timely with respect to the release of the Global Burden of Disease Study, 2010, recently published in the Lancet. [2] This study properly assessed the impact of HBV in the context of the relative risk factors for cirrhosis and liver cancer deaths. The study found that HBV ranks as the 15th cause of death globally.

Effective control and treatment strategies for chronic hepatitis B (CHB) require a thorough understanding of its natural history. An important basis for this understanding includes insights into how the virus replicates and the impact of the 10 different genotypes (A–J) now recognized in the human HBV family. In the first article, the authors review the literature on the role of these different genotypes on disease outcomes as well as possible utility in treatment decision making. The next contribution introduces the reader to some of the new developments in the molecular virology of HBV with the goal of providing a framework to understand how existing antiviral therapies work and to uncover new targets, especially with the identification of a receptor for HBV, the sodium taurocholate coprocessing polypeptide (NTCP). Building on this framework is the article on new therapeutic targets and drugs, in which the authors outline what is in “the pipeline” and what prospects are on the horizon for new therapies for CHB. The recent surge in molecular diagnostics has provided the clinician with the tools to accurately stage patients with CHB. Tests for quantitative HBV DNA and HBsAg levels are robust diagnostic tools that now allow the physician and the patient to reconsider current and future treatment end points, including declining serum HBsAg levels and even its loss. The application of next-generation sequencing platforms provides further understanding in pathogenesis as well as the “dynamics” of emergence of resistance at the quasispecies level.

With the approval and wider availability of highly potent and high genetic barrier drugs such as tenofovir and entecavir, antiviral drug resistance and all its associated challenges and complexities are rapidly receding. The clinical practice guidelines (CPG) for the three major societies AASLD, EASL, and APASL are all in accord with this first-line therapeutic approach and the authors of the article providing a treatment update of CHB strongly reinforce these messages. However, we are left with the treatment of special groups such as highly viremic pregnant women and patients who are immunosuppressed. The review on antiviral use in pregnancy provides an excellent framework for the managing physician, even though endorsed CPGs are yet to be fully promulgated.

HBV is an oncogenic virus and the mechanisms of transformation of the hepatocyte to cancer are complex, with both direct and indirect pathways operating. However, the important take-home message is that potent and effective antiviral therapy that results in undetectable levels of serum HBV DNA for at least 4 years appears to reduce the risk of liver cancer by over 50%. Thus, the stage is set to achieve the aims of the WHO GHP; all that is required now is the will and determination of all persons involved in controlling and preventing CHB in our patients.

 
  • References

  • 1 World Health Organization. Prevention and Control of Viral Hepatitis Infection: A Framework for Global Action. Geneva, Switzerland: World Health Organization; 2012
  • 2 Lozano R, Naghavi M, Foreman K , et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2095-2128