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Hépato-Gastro & Oncologie Digestive

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Therapeutic monotherapy strategy in HBe Ag positive and negative patients Volume 14, supplement 5, Numéro spécial : Prise en charge de l’hépatite chronique B en 2007

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Service d’Hépatologie, Inserm U773 CRB3, Université Paris VII, Hôpital Beaujon, 92110 Clichy

In recent years, marked progress has been made in the treatment of chronic hepatitis B. Several agents are currently approved : interferon alpha (IFN), pegylated interferon alpha-2a (PEG-IFN α2a), lamivudine, adefovir, entecavir and soon telbivudine. Each agent has advantages and inherent limitations. IFN and PEG-IFN α2a have the advantage to induce a sustained virologic response after a defined, self-limited course of treatment. However, these agents are effective in a minority of patients and have frequent side effects that limits tolerability. Analogues have the advantages of oral administration and excellent safety profiles with very high antiviral effect. However, these drugs need to be indefinitely administered since withdrawal of therapy is generally associated with reactivation and sustained response is uncommon except in HBe Ag positive patients who developed HBe seroconversion. In case of HBe seroconversion, it is generally recommended to prolonge therapy for at least 24 weeks before its withdrawal. The efficacy of lamivudine is limited by the emergence of lamivudine-resistant HBV. Adefovir is associated with low incidence of resistance but its antiviral effect is not optimal. Entecavir has recently been approved in Europe. This antiviral agent showed an increased effectiveness against HBV with favourable safety profile and low incidence of resistance. Telbivudine may have enhanced potency and lower rates of resistance than lamivudine but its resistance rates are significantly higher to those of other approved agents. Tenofovir is not yet approved for chronic hepatitis B but several studies suggest that its resistance profile and its anti-HBV efficacy are better than those of adefovir. The future of chronic hepatitis B therapy seems to be in the combination of different drugs. More potent drugs and new combinations together with the understanding of the mechanisms of viral resistance awaits further study to improve the efficacy of treatment and decrease in the future the global burden related to chronic hepatitis B.