Neue Ansätze in der Hepatitis B-Therapie

Zusammenfassung

Eine Interferontherapie über 6 Monate gilt weiterhin als Standardtherapie für chronisch Hepatitis B-Virus (HBV) infizierte Patienten mit günstigen prognostischen Faktoren und fehlenden Kontraindikationen. Ob pegyliertes Interferon (PEG-IFN) verglichen mit herkömmlichen Interferon (IFN), ähnlich wie bei der Therapie der Hepatitis C auch bei der Hepatitis B die Ansprechrate steigern kann, ist derzeit noch unklar. Bei Kontraindikationen gegen Interferon oder ungünstiger klinischer Konstellation sollte Lamivudin gegeben werden. Diese Therapie hat ein günstiges Nebenwirkungsprofil, muss jedoch bei vielen Patienten als Dauertherapie gegeben werden. Unter einer Langzeitbehandlung kommt es gehäuft zur Resistenzentwicklung und damit Wirkungsabschwächung. Das kürzlich in Deutschland zur Behandlung der chronischen HBV-Infektion zugelassene Adefovir stellt eine Alternative besonders bei Lamivudinresistenz dar. Spezifische Mutationen unter der Therapie mit Adefovir wurden bislang nur in Einzelfällen beobachtet. Tenofovir und Emtricitabine sind Substanzen, die zur Human Immunodeficiency Virus (HIV)-Therapie zugelassen sind, und darüber hinaus gute Wirksamkeit gegen HBV zeigen. Weitere Nukleotid- bzw. Nukleosidanaloga mit teilweise sehr hoher inhibitorischer Potenz sind Entecavir, Clevudine und L-Thymidine (L-dT). Die Wirksamkeit gegen Lamivudin-resistente HBV-Stämme ist bisher für Adefovir, Tenofovir, Entecavir und ACH 126 - 443 (ß-L-Fd4C) nachgewiesen.

Insgesamt stehen damit nunmehr mehrere hochaktive Substanzen zur Therapie der chronischen HBV-Infektion zur Verfügung bzw. befinden sich kurz vor der Zulassung. Wahrscheinlich werden in Zukunft Kombinationstherapien, bestehend aus verschiedenen Substanzen oder Substanzklassen, ähnlich wie bei der HIV-Therapie, weitere Fortschritte in der Behandlung der chronischen HBV-Infektion bringen.

Summary

In patients with chronic hepatitis B virus infection and suitable serologic characteristics treatment of choice is interferon alpha for a duration of 6 months. It is as yet unproven whether pegylated interferon improves response rates in comparison to standard-IFN, as in the treatment of hepatitis C virus infection. Patients with cotraindications for IFN-therapy or with prognostic unfavourable characteristics should be treated with lamivudine. This therapy is tolerated well but has to be given for many years. Drug resistance against lamivudine is common and increases with duration of therapy. Adefovir is a new agent which has recently been approved for the treatment of HBV infection and is the treatment of choice in patients with resistance against lamivudine. Adefovir associated mutations have been demonstrated only rarely. Tenofovir and Emtricitabine are substances which are approved for the therapy of HIV infection and exibit strong antiviral activity against HBV. Further agents with inhibitory activity against HBV are Entecavir, Clevudine, and L-dt. Different clinical trials with these promising new compounds are in progress. Agents effective against Lamivudine-resistant strains are Adefovir, Tenofovir, Entecavir, and ß-L-Fd4C.

In conclusion, there are many agents highly active for treatment of chronic HBV infection. Combination regimen including different substances, similar to therapy in HIV infected individuals, might lead to even higher response rates in the treatment of chronic HBV infection in the near future.

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