Heilung der chronischen Virushepatitis B und C: Vision versus Realität

Zusammenfassung

Etwa 500 Millionen Menschen sind chronisch mit dem Hepatitis B oder C Virus (HBV bzw. HCV) infiziert. Die chronische Hepatitis B bzw. C kann über eine chronische Leberentzündung und eine Leberzirrhose bis zum hepatozellulären Karzinom (HCC) führen. Grundlagenwissenschatlichen Erkenntnissen zum Lebenszyklus von HCV ermöglichten die Entwicklung direkt-antiviraler Therapien, die heute bei der großen Mehrheit der Patienten eine Virusausheilung ermöglicht. Eine wichtige Herausforderung für die Zukunft ist die Entwicklung einer HCV-spezifischen Impfung. Der Lebenszyklus von HBV beinhaltet eine Integration der viralen cccDNA in den Zellkern der Hepatozyten. Aufgrund dieses Persistenzreservoirs ist eine Virusausheilung bei der chronischen Hepatitis B selten zu erreichen; Therapieziel bei der Therapie mit pegyliertem Interferon-alfa oder Nukleosid-/ Nukleotidanaloga ist die dauerhafte Virussuppression. Die kürzliche Entdeckung des HBV-Zellrezeptors sowie immunmodulatorische Strategien könnten zur Optimierung der HBV-Therapie bis hin zur Viruselimination beitragen.

Abstract

Approximately 500 million individuals are chronically infected with hepatitis B or C virus (HBV or HCV). Chronic hepatitis B or C can cause liver inflammation, cirrhosis, and ultimately hepatocellular carcinoma (HCC). Advances in basic science regarding the HCV life cycle contributed to the development of direct-acting antivirals, allowing viral elimination in the large majority of currently treated patients. A major challenge for future research is the development of an HCV-specific vaccination. The HBV life cycle involves the integration of viral cccDNA into the nucleolus of the hepatocytes. Due to this reservoir of persistence, viral elimination is rarely achieved during chronic HBV infection. Aim of antiviral therapy based on pegylated interferon-alfa or nucleoside / nucleotide analogues is a sustained viral control. The recent identification of the HBV cell receptor as well immunomodulatory strategies may help to optimize HBV therapy and eventually allow viral elimination.

Schlüsselwörter

Hepatitis B - Hepatitis C - molekulare Virologie - Pathogenese - antivirale Therapie

Keywords

Hepatitis B - hepatitis C - molecular virology - pathogenesis - antiviral therapy

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