Effect of newer oral antiviral agents on future therapy of chronic hepatitis B

Long-term therapy with oral nucleoside/nucleotide analogues (NAs) is a favoured approach to the treatment of patients with chronic hepatitis B (CHB); however, all oral agents currently approved for the treatment of such patients are associated with some risk for drug resistance. This can lead to a rebound in HBV levels and, eventually, progressive liver disease. Combination therapy is one strategy that has the potential for enhanced antiviral effects and diminished or delayed resistance. The disadvantages of combination therapy include increased cost, the potential for drug interactions and increased toxicity. Additional therapeutic efficacy from combination therapy has not been demonstrated in clinical trials of HBV, and this approach might be less relevant now that potent NAs with excellent drug resistance profiles are available. However, it might be possible to identify subsets of patients (for example, those with extremely high viraemia or low baseline alanine aminotransferase levels) who derive added benefit from combination therapy. This review examines efficacy and resistance data for new low resistance oral NAs and clinical experience to date with de novo combination therapy in patients with CHB. The application of combination therapy in select populations of patients with CHB is also discussed.