Direkt antivirale Therapieansätze bei der chronischen Hepatitis C

Zusammenfassung

Die antivirale Therapie der chronischen Hepatitis C besteht seit etwa 10 Jahren aus der Kombination von pegyliertem Interferon-alfa (PegIFN) sowie Ribavirin. Diese Therapie führt bei nur 40–50 % der Patienten mit einer Infektion mit dem Hepatitis-C-Virus (HCV) des Genotyps 1 sowie bei ca. 80 % der Patienten mit HCV-Genotyp 2 oder 3 zu einer anhaltenden Viruselimination. Deshalb wurden in den letzten Jahren u. a. direkt antiviral wirksame Substanzen für die Therapie von Patienten mit einer chronischen HCV-Genotyp-1-Infektion entwickelt. Diese Substanzen hemmen verschiedene für die Virusreplikation essenzielle virale Proteine, wie z. B. die NS3/4A-Protease, die NS5B-Polymerase und das NS5A-Protein. Die beiden NS3/4A-Protease-Inhibitoren Telaprevir und Boceprevir wurden als erste Vertreter dieser Substanzklasse vor kurzem zur Therapie der chronischen HCV-Genotyp-1-Infektion in Kombination mit PegIFN und Ribavirin zugelassen. Diese Tripeltherapie führt bei ca. 70 % der Patienten mit HCV-Genotyp 1 zu einer anhaltenden Viruselimination. Es ist zu erwarten, dass weitere direkt antivirale Substanzen alleine oder in Kombination in wenigen Jahren zur klinischen Anwendung kommen und eventuell sogar eine IFN-freie Therapie ermöglichen.

Abstract

The standard antiviral therapy for chronic hepatitis C is pegylated interferon-alfa (PegIFN) and ribavirin since about 10 years. This treatment regimen leads to a sustained virological response (SVR) in 40–50 % of patients infected with HCV genotype 1 and in approx. 80 % of those infected with HCV genotype 2 or 3.  In recent years, many direct antiviral agents (DAA) have been developed and are being explored in clinical studies. These antiviral agents target different viral proteins that are central for HCV replication, incl. the NS3/4A protease, NS5B polymerase, and the NS5A protein. The protease inhibitors telaprevir and boceprevir have recently been approved for the treatment of chronic HCV genotype 1 infection in combination with PegIFN and ribavirin. These triple therapies increase the SVR rates in HCV genotype 1 patients from 40–50 % to approx. 70 %. Other DAAs will likely be approved in the near future and may result in an IFN-free antiviral therapy.

Schlüsselwörter

Hepatitis-C-Virus - antivirale Therapie - Protease-Inhibitoren - Telaprevir - Boceprevir

Keywords

Hepatitis C virus - antiviral therapy - protease inhibitors - telaprevir - boceprevir

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