Therapy for chronic hepatitis B. Present status.

Abstract

Up to now Interferon (IFN) has been the only licensed treatment for chronic type B and D viral hepatitis. However, IFN monotherapy is efficacious only in HBeAg positive chronic hepatitis B and is aggravated by important side effects in many patients. To overcome the limits of IFN monotherapy, combination therapies of this cytokine together with other synergistic drugs have been proposed and many antivirals that directly act on Hepatitis B Virus (HBV) synthesis have been developed. Combination therapies with acyclovir, levamisole, and cortisone have not been more advantageous than IFN alone. Of the antivirals, Adenine Arabinoside monophosphate, though active against HBV, causes severe neurotoxicity and Famciclovir has not shown significant efficacy in a large multicenter study of chronic HBeAg positive hepatitis. Lamivudine appears the most promising in terms of clinical benefit, safety and tolerance. It is active on wild type HBV as well as on HBeAg-minus variants of the virus. However, although HBV is consistently repressed while on therapy, only a part of the patients are cured or remain in remission after Lamivudine withdrawal. Maintenance therapy is in order, but the long-term use of Lamivudine is complicated by the emergence of polymerase gene-mutants which may recapitulate disease. Combination with other antivirals active also against Lamivudine escape mutants opens promising new prospects. There is as yet no valid therapy for chronic HDV hepatitis; IFN is of no benefit in most cases.