[Treatment of chronic hepatitis B]

In recent years, marked progress has been made in the treatment of chronic hepatitis B. Several agents have been approved: interferon alpha-(IFN), pegylated interferon alpha2a (PEG-IFN alpha2a), lamivudine, adefovir, entecavir, telbivudine and recently, tenofovir. Each drug has advantages and limitations. IFN and PEG-IFN alpha2a have the advantage of inducing a sustained virologic response after a defined, limited course of treatment. However, these drugs are only effective in a minority of patients and have frequent side effects. Analogues have the advantage of being administered orally, with good safety profiles and a potent antiviral effect. However, these drugs need to be administered indefinitely since withdrawal of therapy is generally associated with reactivation, and a sustained response is uncommon except in HBeAg positive patients who develop HBe seroconversion. In case of HBe seroconversion, therapy should usually be continued for at least another 24 weeks. The efficacy of lamivudine is limited by the emergence of lamivudine-resistant HBV. Adefovir is associated with a moderate incidence of resistance but its antiviral effect is not optimal. Entecavir has shown to be more effective with a favourable safety profile and a low incidence of resistance. Telbivudine is more potent and has a lower rate of resistance than lamivudine but the resistance rate is significantly higher than other approved drugs. Tenofovir has a potent antiviral effect with a good resistance profile. The future of chronic hepatitis B therapy appears to be different drug combinations. Normally the advantage of drug combinations versus monotherapy should be additive or synergistic antiviral effects and a decrease in viral resistance. Unfortunately, there are few data available and none of the evaluated analogue combinations have been shown to be better than monotherapy. The only combination which has shown a synergistic effect is of pegylated interferon alpha2a with lamivudine. Therefore, combinations of pegylated interferon with the most potent analogues need to be evaluated. The ultimate goal of therapy is HBsAg seroconversion which is more often observed with interferon. Indeed, quantification of serum HBsAg will be a useful tool to predict the treatment outcome. More potent drugs and new combinations as well as understanding the mechanisms of viral resistance should be evaluated to improve the efficacy of treatment.