The Control of Chronic Hepatitis B: The Role for Chemoprevention

It has been almost 40 years since the discovery of the hepatitis B virus (HBV) and yet the disease it causes, hepatitis B, remains a major public health challenge. Despite the development of an effective vaccine and its implementation throughout the 1980s, there is still a huge burden of liver disease due to chronic hepatitis B (CHB). Worldwide, more than 400 million people have CHB; the majority are in the Asia-Pacific region, and there are at least one million deaths each year as a direct consequence of infection. The main public health strategy to control hepatitis B for the last 20 years has been primary prevention through vaccination, and excellent progress has been made. However, to reduce the complications of CHB, which include the development of cirrhosis with hepatic decompensation and hepatocellular carcinoma (HCC) for the at-risk population, an additional strategy is urgently required. The World Heath Organization (WHO) has termed this strategy chemoprevention, which is the use of antiviral agents to control HBV replication and thereby block the development of the complications that make HBV infection the ninth leading cause of death worldwide.

This issue of Seminars in Liver Disease is devoted to the implementation of this strategy of chemoprevention. Effective treatment of CHB requires a thorough understating of the natural history of chronic HBV infection and a number of articles have been written by experts who manage CHB and its associated clinical sequelae using the increasing range of treatment options available in 2006. Drs. Feld and Heathcote introduce and discuss hepatitis B e antigen (HBeAg)-positive CHB, whereas Drs. Hadziyannis and Papatheodoridis review HBeAg-negative CHB. There is a deliberate overlap in these two articles reflecting the continuum of the various phases of CHB. Drs. Chia-Ming Chu and Yun-Fan Liaw review recent progress in managing patients with cirrhosis and emphasize the clinical imperative for effective control of HBV replication. Drs. Henry Chan and Joseph Sung update the reader on the molecular pathogenesis of HCC and the new directions that therapies for this challenging condition are heading.

With the emphasis in this issue on chemoprevention, the pressing challenge in 2006 is management of drug failure and drug resistance. Two articles describe specific issues surrounding antiviral drug resistance. First, Drs. Batholomeusz and Locarnini propose the use of standardized terminology of case definitions of drug failure and drug resistance, and adoption of this terminology by treating physicians. Professor Zoulim reviews in vitro models for studying resistance, and introduces the reader to the possible role for phenotypic testing in patient management. The use of HBV DNA testing is pivotal for the development of standardized terminology and patient management, and Dr. Bowden reviews the new molecular-based assays for HBV DNA measurement. He makes a very strong argument for the adoption of a universal unit of measurement developed by WHO, the international unit (units per milliliter) for HBV DNA testing.

The success of highly active antiretroviral therapy for the treatment of patients with human immunodeficiency virus infection is based on the use of multiple drugs that have different sites of action. In CHB, the licensed therapies include only two classes: the immune-based therapies, such as interferon, and the antiviral-based drugs, such as nucleos(t)ide analogues. Clearly, other drug targets are required, and Dr. Tim Harrison introduces and updates the reader concisely on the molecular virology of HBV. Drs. Kumar Visvanathan and Sharon Lewin present a balanced view on hepatitis B immunopathogenesis, which includes the role of the innate immune response. It is the innate immune response that could provide new approaches to patient management in the near future. Drs. Maura Dandri, Marc Lutgehetmann, Tassilo Volz, and Jorg Petersen present the reader with a comprehensive overview of the small animal model systems presently available that can evaluate these new therapies appropriately. Finally, how these new therapeutics will be used and what type of therapeutics will be needed in the future for the successful implementation of chemoprevention is discussed by Drs Chee-Kin Hui and George K.K. Lau.

The goal of chemoprevention for CHB is to improve the quality and the outcomes of care for patients with CHB. On behalf of all of the contributing authors, we hope this issue is an important step in fulfilling that goal.