Ivana Carey1, Phillip M Harrison. 1. Division of Gene and Cell-based Therapy, Department of Liver Studies and Transplantation, King's College London, Denmark Hill Campus, Bessemer Road, London SE5 9PJ, UK.
Abstract
BACKGROUND: Nucleos(t)ide analogues, active against hepatitis B polymerase, suppress viral replication and improve clinical outcome. However, the emergence of drug-resistant mutants can result in treatment failure. OBJECTIVES: We describe how the choice of first-line therapy is critical to long-term treatment success. METHODS: A review of current drug therapies is provided. RESULTS/ CONCLUSIONS: Monotherapy with early-generation drugs (lamivudine or adefovir) was associated with a high rate of viral drug resistance and combination therapy with these agents was shown to reduce the incidence of resistance. The latest-generation drugs (entecavir and tenofovir) are potent inhibitors of viral replication and, in treatment-naive subjects, viral resistance to entecavir is uncommon and is not yet reported to tenofovir. Therefore, monotherapy with either entecavir or tenofovir is the current preferred option in treatment-naive patients. Combination therapy is appropriate in those with drug-resistant HBV infection, where drug choice is guided by the viral drug-resistance genotype/phenotype. Although combination therapy has been advocated in other patient groups (e.g., those with decompensated cirrhosis and following liver transplantation), there are, as yet, no data to mandate the use of combination therapy in such patients and any perceived benefit must be weighed against increased cost and risk for toxicity.
BACKGROUND: Nucleos(t)ide analogues, active against hepatitis B polymerase, suppress viral replication and improve clinical outcome. However, the emergence of drug-resistant mutants can result in treatment failure. OBJECTIVES: We describe how the choice of first-line therapy is critical to long-term treatment success. METHODS: A review of current drug therapies is provided. RESULTS/ CONCLUSIONS: Monotherapy with early-generation drugs (lamivudine or adefovir) was associated with a high rate of viral drug resistance and combination therapy with these agents was shown to reduce the incidence of resistance. The latest-generation drugs (entecavir and tenofovir) are potent inhibitors of viral replication and, in treatment-naive subjects, viral resistance to entecavir is uncommon and is not yet reported to tenofovir. Therefore, monotherapy with either entecavir or tenofovir is the current preferred option in treatment-naive patients. Combination therapy is appropriate in those with drug-resistant HBV infection, where drug choice is guided by the viral drug-resistance genotype/phenotype. Although combination therapy has been advocated in other patient groups (e.g., those with decompensated cirrhosis and following liver transplantation), there are, as yet, no data to mandate the use of combination therapy in such patients and any perceived benefit must be weighed against increased cost and risk for toxicity.