Zusammenfassung
Sowohl für die HBeAg positive als auch für die HBeAg negative chronische Hepatitis B ist derzeit die Therapie mit pegyliertem Interferon die Standardtherapie. Alternativ ist das Nukleosidanalog Lamivudine in der Lage die HBV DNA Spiegel im Serum zu unterdrücken und in bis zu 30 % der Patientin eine Serokonversion in HBeAg-System zu erreichen. Lamivudine ist ferner in HBeAg negativen chronischen Hepatitis B Fällen ähnlich effizient in der Unterdrückung der HBV DNA Replikation als in HBeAg positiven Patienten. Pegyliertes Interferon scheint kurzfristig effektiver zu sein, als Lamivudine Monotherapie. Die häufig gesehene Entwicklung von Lamivudine resistenten HBV Varianten kann nun seit einiger Zeit erfolgreich durch Therapieumstellung auf Adevofir dipivoxil bekämpft werden. Nukleosidanaloge sind üblicherweise besser verträglich als Interferon und können auch bei Patienten mit HBV induzierter Leberzirrhose eingesetzt werden. Es ist zu erwarten, dass in naher Zukunft andere Nukleosidanaloge wie Entecavir, Emtricitabine, Telbivudine oder Clevudine unsere therapeutischen Möglichkeiten gegen Hepatitis B wesentlich erweitern werden. Bei der chronische Hepatitis C ist die Therapie mit pegyliertem Interferon in Kombination mit Ribavirin derzeit Standard. Dieses therapeutische Regime ist aber nur in der Lage bei ca. 50 % der behandlungsnaiven Patienten eine Dauerheilung zu erreichen. Diese beschränkte Effektivität macht die Entwicklung neuer Medikamente notwendig. Kandidaten dafür sind NS3–4a Proteaseinhibitoren oder Inhibitoren der NS5B Polymerase. Darüber hinaus wird versucht die HCV Replikation auch durch auf RNA-Interferenz basierenden siRNA-Inhibitoren oder durch Aktivierung von Tol-like Receptors (TLR), die als Teil des natürlichen Immunsystems eindringende Mikroorganismen erkennen können, zu hemmen. Obwohl derzeit keine dieser therapeutischen Ansätze zu einer zugelassenen Therapie geführt haben, stellen sie erfolgsversprechende Wege für die Zukunft der HCV Therapie dar.
Summary
In chronic hepatitis B treatment with pegylated interferon can now be considered as therapy of choice in both HBeAg positive and HBeAg negative patients and seems to be more effective than lamivudine monotherapy. Alternatively, treatment with lamivudine is able to suppress HBV DNA and to induce HBeAg conversation in up to 30 % of the patients. In HBeAg negative chronic hepatitis B lamivudine has a similar efficiency in suppressing HBV DNA as in HBeAg positive patients. The frequently developing lamivudine resistant HBV variants can now be successfully be treated with adevofir dipivoxil in both forms of chronic hepatitis B. These nucleosides analogues are generally better tolerated than interferon and can also be given in patients with HBV related liver cirrhosis. Our therapeutic armamentarium will be expanded in the near future by other nucleoside analogues such as entecavir, emtricitapine, telbivudine or clevudine. The treatment of choice in chronic hepatitis C currently is pegylated interferon plus ribavirin. This regimen is able to induce a sustained virologic response in 50 % of treatment naïve cases. The limited effectiveness of this therapeutic approach makes additional drugs highly warranted and inhibitors of the NS3–4a protease region or the NS5B polymerase region of the viral genome are under development. In addition, HCV replication inhibitors based on RNA interference (siRNA) or agonists of toll like receptors (TLR), which are part of the inborn immune system recognizing the presence of invading microorganisms, are currently explored as agents active in inhibiting HCV replication. Although none of these drugs are currently licensed for HCV treatment they are promising antiviral candidates for the future.
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Müller, C. Chronic Hepatitis B and C – current treatment and future therapeutic prospects. Wien Med Wochenschr 156, 391–396 (2006). https://doi.org/10.1007/s10354-006-0314-5
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DOI: https://doi.org/10.1007/s10354-006-0314-5
Schlüsselwörter
- Chronische Hepatitis
- Pegyliertes Interferon
- Ribavirin
- Lamivudine
- Adefovir Dipivoxil
- Protease Inhibitoren
- Polymerase Inhibitoren