[Frontiers in Bioscience 16, 225-250, January 1, 2011]

Chronic viral hepatitis: epidemiology, molecular biology, and antiviral therapy

Stevan A. Gonzalez1, Emmet B. Keeffe 2

1Division of Hepatology, Baylor Regional Transplant Institute, Baylor All Saints Medical Center at Fort Worth and Baylor University Medical Center at Dallas, 1400 8th Avenue, Building C - 1st Floor, Fort Worth, TX, USA 76104, 2Division of Gastroenterology and Hepatology, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA, USA 94304-1509

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Hepatitis B
3.1. Epidemiology
3.2. Molecular biology
3.2.1. The hepatitis B virus and genome
3.2.2. Life cycle and viral replication
3.2.3. Impact of specific mutations
3.3. Natural history
3.3.1. Phases of chronic infection
3.3.2. Hepatitis B and hepatocellular carcinoma
3.4. Antiviral Therapy
3.4.1. Indications for therapy
3.4.2. Nucleoside and nucleotide analogues
3.4.3. Interferon alpha
3.4.4. Predictors of response
3.4.5. Antiviral drug resistance
3.4.6. Monitoring virologic response
4. Hepatitis D
4.1. Epidemiology
4.2. Molecular biology
4.2.1. The hepatitis D virus genome and hepatitis D antigen
4.2.2. Life cycle and dependence on hepatitis B
4.3. Natural history
4.4. Antiviral therapy
5. Hepatitis C
5.1. Epidemiology
5.2. Molecular biology
5.2.1. The hepatitis C virus and genome
5.2.2. Life cycle and viral replication
5.3. Natural history
5.4. Antiviral therapy
5.4.1. Combination peginterferon and ribavirin
5.4.1.1. Predictors of response
5.4.1.2. Impact of adherence
5.4.2. Retreatment of failed therapy
5.4.3. Direct Acting Antiviral (DAA) agents
6. Perspective
7. References

1. ABSTRACT

Viral hepatitis is a major cause of chronic liver disease, liver failure, and hepatocellular carcinoma worldwide, resulting in significant morbidity and mortality. New insights into the pathogenesis and molecular biology of hepatitis viruses have led to the discovery of novel antiviral agents. Likewise, a greater understanding of the natural history of chronic infection, predictors of disease progression, and predictors of virologic response to therapy has resulted in more effective treatment strategies. Recent data have increasingly demonstrated that the ability to achieve a successful response to antiviral therapy may significantly reduce the risk of progressive liver disease and hepatocellular carcinoma. Immunization practices and the use of potent antiviral therapy may have a major impact in reducing the burden of chronic liver disease and the incidence of hepatocellular carcinoma associated with chronic hepatitis B and chronic hepatitis D. Individualized treatment strategies and the development of direct acting antiviral agents may lead to further improvements in the ability to achieve a sustained virologic response to therapy in chronic hepatitis C. With new advances in the treatment of chronic hepatitis, efforts to optimize viral suppression while reducing the potential for antiviral drug resistance will become increasingly important.