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Neue Entwicklungen in der Therapie der Hepatitis B

New developments in the treatment of hepatitis B

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Zusammenfassung

Derzeit können 2 Klassen antiviraler Medikamente für die chronische Hepatitis B (CHB) unterschieden werden: pegyliertes Interferon-α (PEG-IFN) und Nukleosid-/Nukleotidanaloga (NA). Die wichtigsten Vorteile der NA-Therapie sind ihre gute Verträglichkeit, ihre potente antivirale Aktivität und die hohen Erfolgsraten. Für PEG-IFN sprechen die Begrenzung der Behandlungsdauer, fehlende Resistenzen gegen den Wirkstoff sowie die Möglichkeit eines anhaltenden Effekts auch über das Therapieende hinaus. Mithilfe der HBsAg-Quantifizierung können Entwicklungen hin zu einer klinischen Heilung ohne Viruseradikation (HBsAg-Verlust) mittlerweile besser untersucht und damit stärker hinterfragt werden. Die Kombination beider Wirkstoffklassen – zumindest theoretisch ein vielversprechender Ansatz – mit dem Ziel des HBsAg-Verlusts wird in letzter Zeit stärker untersucht und kann zeitgleich, simultan als sequenzielle Therapie (Add-on-Ansatz) oder als Wechsel der Wirkstoffklassen (Switchansatz) erfolgen. Weiterhin wurden bereits NA-Kombinationen in ausgesuchten klinischen Situationen untersucht. Einige Studien konnten Vorteile von Kombinationsstrategien zur Behandlung der CHB zeigen. Es fehlen jedoch immer noch die entscheidenden prospektiven Studien, die einen klinischen Langzeitnutzen eindeutig belegen könnten. Schließlich wird auch das Stoppen oder Pausieren der NA-Therapie erstmals in prospektiven Studien evaluiert. Die Entwicklung weiterer antiviraler Substanzen, wie Kapsidinhibitoren, Entryinhibitoren, siRNA oder Toll-like-Rezeptor(TLR)-Agonisten, ist von der klinischen Anwendung noch relativ weit entfernt und soll deshalb an dieser Stelle nicht ausführlich diskutiert werden.

Abstract

Currently available antiviral treatment for chronic hepatitis B (CHB) infection can be divided into two classes of therapeutic agents: pegylated interferon α (PEG-IFN) and nucleoside/nucleotide analogues (NAs). The major advantages of NAs are good tolerance and potent antiviral activity associated with high rates of on-treatment response to therapy. The advantages of PEG-IFN include a finite course of treatment, the absence of drug resistance, and an opportunity to obtain a durable posttreatment response to therapy. The quantification of HBsAg became a robust tool in recent years measuring the aspect of remaining replication capability and clinical cure. The use of these two antiviral agents with different mechanisms of action in combination is theoretically an attractive treatment approach, either simultaneously, as sequential combination therapy (add-on), or even as an immediate switch from one agent to the other. Different NAs have also been combined in certain clinical situations. At present, several studies have confirmed certain virological advantages of combination therapies, but pivotal prospective studies demonstrating long-term clinical benefit for patients are still lacking. Finally, the stopping of long-term NA treatment was recently studied in preliminary prospective trials. The clinical development of novel agents such as capsid or entry inhibitors, siRNAs, or Toll-like receptor (TLR) agonists is still at an early stage and, therefore, are not discussed in this article.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. J. Petersen gibt an Forschungsunterstützung von den Firmen Bristol-Myers Squibb, Novartis und Roche erhalten zu haben. Er führte klinische Studien mit Unterstützung durch die Firmen AbbVie, Bristol-Myers Squibb, Boehringer, Gilead, Janssen, Merck, MSD Sharp & Dohme, Roche, Siemens und Vertex durch. Er ist als Berater für die Firmen Abbott, AbbVie, Bristol-Myers Squibb, Boehringer, Gilead, GlaxoSmithKline, Kedrion, Janssen, Merck, MSD Sharp & Dohme, Novartis und Roche tätig und hat gesponserte Vorträge für die Firmen Abbott, AbbVie, Bristol-Myers Squibb, Boehringer, Gilead, Kedrion, Janssen, Merck, MSD Sharp & Dohme, Novartis und Roche gehalten.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Leberzentrum Hamburg, IFI Institut für Interdisziplinäre Medizin, Asklepios Klinik St. Georg Haus L, Lohmühlenstr. 5, 20099, Hamburg, Deutschland

    J. Petersen

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Petersen, J. Neue Entwicklungen in der Therapie der Hepatitis B. Gastroenterologe 10, 284–291 (2015). https://doi.org/10.1007/s11377-015-0999-3

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