Koinfektionen bei Hepatitis

Hepatitis D

Natürlicher Verlauf

Konsens

Die akute Hepatitis D nimmt häufig einen schwereren Verlauf als die akute Hepatitis-B-Monoinfektion (B). Die HDV-Superinfektion verläuft im Vergleich zur HDV/HBV-Simultaninfektion häufiger chronisch (B).

Die chronische Hepatitis D führt, verglichen mit der Hepatitis-B-Monoinfektion, häufiger und rascher zur Zirrhose (B). Die Leberzirrhose bei Hepatitis D weist im Vergleich zur Leberzirrhose bei Hepatitis-B-Monoinfektion eine erhöhte Dekompensationsneigung und ein höheres Risiko für ein hepatozelluläres Karzinom auf (B).

Erläuterung

Weltweit wird geschätzt, dass 5 % der HBsAg-Träger mit dem Hepatitis-D-Virus koinfiziert sind [1]. Die Prävalenz der Hepatitis D unter HBsAg-Trägern zeigt eine große geografische Schwankungsbreite und hängt zudem vom Risikoprofil der untersuchten Population ab. So schwankt die HDV-Prävalenz in Deutschland zwischen 0,3 % bei HBsAg-positiven Blutspendern und 40 % bei HBsAg-positiven Drogenabhängigen [2] [3]. In Deutschland wird die Prävalenz der Hepatitis D zunehmend von Einwanderern aus den osteuropäischen Staaten und den Staaten der ehemaligen Sowjetunion bestimmt [4].

Die Schwere und fulminante Verläufe sind bei der akuten Hepatitis D häufiger als bei der akuten Hepatitis-B-Monoinfektion [5] [6] [7] [8]. Die HDV-Superinfektion führt häufiger (bis zu 90 % der Fälle) zur Chronizität [9] [10] als die HBV/HDV-Simultaninfektion.

Mit einer Ausnahme [11] zeigen Untersuchungen, dass die chronische Hepatitis D im Vergleich zur HBV-Monoinfektion ungünstiger verläuft [7] [12] [13] [14] [15]. Die Progression zur Leberzirrhose findet ca. 10 - 15 Jahre früher statt als bei der alleinigen Hepatitis B [14] [16]. Nach Eintritt eines zirrhotischen Leberumbaus ist das Risiko für eine Leberdekompensation und die Entstehung eines hepatozellulären Karzinoms bei der Hepatitis D im Vergleich zur HBV-Monoinfektion erhöht [13] [14]. Die 5-Jahres-Mortalität ist bei Patienten mit Hepatitis D gegenüber Patienten mit Hepatitis B ungefähr verdoppelt [13] [14].

Therapie

Konsens

Trotz einer gewissen Besserung (Transaminasen, Histologie) wird eine dauerhafte Elimination des HDV durch eine Therapie mit konventionellem Interferon (z. B. 3 × 9 - 10 Millionen Einheiten/Woche s. c. für die Dauer von 12 Monaten) nur selten erreicht (A).

Für die Behandlung der Hepatitis D mit Famciclovir, Lamivudin oder Ribavirin allein oder in Kombination mit Interferon gibt es keine fundierte Grundlage (B).

Bei Patienten mit fortgeschrittener Leberzirrhose ist die Transplantation eine Therapieoption (B).

Erläuterung

Daten zur Auswirkung der Interferontherapie auf den Langzeitverlauf (hepatische Dekompensation, HCC-Entwicklung, Überleben) der Hepatitis D liegen nicht vor. Welche Faktoren ein Ansprechen auf die Interferontherapie begünstigen, ist nicht systematisch untersucht. Verfügbare Therapiestudien weisen zudem kleine Fallzahlen auf. Die Interferontherapie über 12 Monate führt bei 6 - 66 % der Patienten zu einer virologischen ETR (end of treatment response), bei weniger als 10 % der Patienten zur dauerhaften Elimination des HDV [17] [18] [19] [20] [21] [22]. Während der IFN-Therapie werden eine Normalisierung der Transaminasen in 12 - 70 % der Fälle und eine Verbesserung der Leberhistologie beobachtet [17] [18] [19] [20] [21]. Die Normalisierung der Transaminasen kann auch nach Beendigung der Therapie trotz persistierender Virämie andauern und mit einer Fibroseregression verbunden sein [20] [22]. Ob eine lang dauernde Interferon-Therapie (> 12 Monate) bei der Hepatitis D sinnvoll ist [23], bleibt zu klären, ebenso wie der Stellenwert neuer Interferone.

Für Lamivudin, Famciclovir, Ribavirin und eine Lamivudin-Interferon-Kombinationstherapie konnte in Pilotstudien an kleinen Patientenzahlen ein biochemisches oder virologisches Ansprechen nicht nachgewiesen werden [24] [25] [26] [27].

Bei Patienten mit fortgeschrittener Leberzirrhose sollte eine Lebertransplantation erwogen werden. Sie zeigt bei HDV/HBV-Koinfizierten 5-Jahres-Überlebensraten bis zu 90 %, eine vergleichsweise geringe Reinfektions- und niedrige Abstoßungsrate [28] [29] [30] [31].

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