Die molekularen Mechanismen der Replikation des Hepatitis C Virus – Implikationen für die Entwicklung antiviraler Wirkstoffe

Zusammenfassung

Die chronische Infektion mit dem Hepatitis-C-Virus (HCV) ist auch mehr als 20 Jahre nach seiner Entdeckung ein wichtiges medizinisches Problem. 120 – 180 Millionen Menschen weltweit sind nach Schätzungen der Weltgesundheitsorganisation chronisch mit HCV infiziert, wovon etwa 5 Millionen Menschen in Westeuropa leben. Diese haben ein hohes Risiko für die Entwicklung einer Leberzirrhose oder eines hepatozellulären Karzinoms (HCC). Die aktuelle Therapie hat zahlreiche Limitationen und ein Vakzin ist nicht in Sicht. Intensive Forschungsaktivitäten, insbesondere die Entwicklung adäquater Zellkultursysteme, haben neue Einblicke in den viralen Vermehrungszyklus ergeben sowie grundlegende Strategien identifiziert, mit denen das Virus vermutlich der immunologischen Kontrolle entkommt. Adäquate Zellsysteme lieferten auch die Grundlage für die Entwicklung potenter und selektiver Wirkstoffe zur Behandlung der chronischen Hepatitis C und man rechnet 2011 / 2012 mit der Zulassung der NS 3 / 4A-Proteaseinhibitoren der ersten Generation. Dennoch gibt es eine Reihe wichtiger und bis heute ungeklärter Fragen, deren Beantwortung Forscher wie Kliniker die nächsten Jahre noch beschäftigen wird.

Abstract

More than 20 years after the discovery of the hepatitis C virus (HCV), chronic hepatitis C still is a major medical problem. According to the World Health Organisation 120 to 180 million people are chronically infected with HCV, with 5 million infected individuals living in Western Europe. These people have a high risk to develop serious liver disease such as liver cirrhosis and hepatocellular carcinoma (HCC). The standard-of-care therapy is not satisfying and there is no vaccine in sight. Owing to intense research activities, most notably the development of adequate cell culture systems, important insights into the viral replication cycle have been gained and several strategies used by HCV to overcome immune responses have been identified. Adequate cell culture systems also provided the basis for the development of potent and selective antivirals for treatment of chronic hepatitis C and it is expected that NS 3 / 4A protease inhibitors will be approved for clinical use in 2011 / 2012. Nevertheless, important questions are still unanswered and they will keep clinicians and basic researchers busy for the coming years.

Schlüsselwörter

Leber - Hepatitis C - antivirale Wirkstoffe - HCV-Replikation - HCV-Wirt-Interaktion

Key words

liver - hepatitis C - antiviral drugs - HCV replication - HCV-host interaction

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