Antiviral Therapy

Richman, Douglas D

doi: 10.1177/135965350701203s01pmid: N/A

McGovern, Barbara H

doi: 10.1177/135965350701203s02pmid: N/A

Approximately 350 million people have chronic hepatitis B infection, a leading cause of cirrhosis and hepatocellular carcinoma (HCC). Patients who are infected through parenteral or sexual transmission are also at risk for acquisition of HIV. Concomitant HIV infection can lead to an increased risk of morbidity and mortality from hepatitis B virus (HBV)-related cirrhosis, end-stage liver disease and HCC. This review will focus on the epidemiology, natural history and prevention of HBV infection and the modulating effect of HIV on the clinical expression of HBV disease.

Locarnini, Stephen; Warner, Nadia

doi: 10.1177/135965350701203s03pmid: N/A

The two key events in the life-cycle of the hepatitis B virus (HBV) involve (1) the generation from viral genomic DNA of the covalently closed circular DNA transcriptional template, and (2) the reverse transcription of the viral pregenomic RNA to form the HBV DNA genome. Diversity in the HBV genome is ensured by the low fidelity of the viral reverse transcriptase (rt). Particular selection pressures such as antiviral therapy readily select out escape mutants from this pre-existing quasispecies pool. Antiviral drug resistance in chronic hepatitis B can be caused by many factors, including the viral mutation frequency, the intrinsic mutability of the antiviral target site, the selective pressure exerted by the drug, the magnitude and rate of virus replication, the overall replication fitness of the mutant, the genetic barrier of the >compound and the availability of replication space. In the setting of HIV coinfection, the rate of replication is increased by one to two orders of magnitude, accelerating the emergence of drug resistance in this setting. The HBV genome is arranged into frame-shifted and overlapping reading frames in such a manner that antiviral drug-resistance-associated changes in the rt can result in changes in the viral envelope protein. These HBV isolates with altered surface antigens exhibit reduced binding of specific and neutralizing antibody and so have diagnostic and public health implications, especially in the setting of HIV coinfection where the risk of transmission is increased. Thus, prevention of resistance requires the adoption of strategies that effectively control virus replication, including the use of combination chemotherapy.

Thio, Chloe L

doi: 10.1177/135965350701203s04pmid: N/A

With the recent approval of several drugs for the management of chronic hepatitis B, the proper diagnosis and classification of this disease is necessary to determine if therapy is needed and what the best treatment options are. The diagnosis of chronic hepatitis B relies on serological testing, and disease stage is further characterized with HBV DNA levels and an assessment of liver disease through biopsy or non-invasive methods. A regular screening protocol is necessary for patients with chronic hepatitis B to monitor the development of cirrhosis and hepatocellular carcinoma. Patients receiving treatment also need regular monitoring for response to determine if a different therapeutic regimen is needed or if drug-resistant variants are being selected. This review discusses the various tests for hepatitis B diagnosis and for monitoring disease progression and treatment response. In addition, noninvasive methods for classifying liver disease stage are discussed, as are special considerations that are needed for individuals coinfected with HIV.