HCV-Reinfektion nach Lebertransplantation

Zusammenfassung

Hintergrund und Fragestellung: Die Reinfektion mit dem Hepatitis-C-Virus (HCV) nach Lebertransplantation (LTx) ist eine große klinische Herausforderung. Für Patienten, die mit dem HCV-Genotyp (GT) 1 infiziert sind, konnte die Einführung Proteaseinhibitor(PI)-basierter Therapien das Ansprechen signifikant verbessern. In der Studie werden die vorläufigen Erfahrungen eines Zentrums mit der Telaprevir-basierten Triple-Therapie nach LTx dargestellt.

Patienten und Methode: 13 Patienten (mittleres Alter 53 Jahre, 10 Männer) mit histologisch gesicherter HCV-GT1-Reinfektion nach LTx wurden mit einer PI-basierten Triple-Therapie behandelt. Das Therapieschema bestand aus PEG-Interferon (IFN)/Ribavirin (RBV)/Telaprevir (TVR) für 12 Wochen, gefolgt von einer dualen Therapiephase für weitere 12 Wochen. Während der Triple-Therapie wurde die Immunsuppression engmaschig überwacht; ferner erfolgten regelmäßige Kontrollen hinsichtlich Nebenwirkungen.

Ergebnisse: Bei allen Patienten war eine signifikante Reduktion der Dosis der Immunsuppressiva notwendig (TAC 30-fach; CSA 3,5-fach). Gleichmäßige Spiegel wurden durch die tägliche bis übertägige Dosis einer Sondergröße von 2–4 × 0,1 mg/d Tacrolimus erreicht bzw. einer Mindestmenge von 2 × 10 mg/d CSA. Bei etwa 65 % der Patienten traten Blutbildveränderungen auf, die eine RBV-Dosisreduktion, die Gabe von Erythropoetin oder die Transfusion von Erythrozytenkonzentraten notwendig machte. Bei etwa der Hälfte der Patienten war ein deutlicher Anstieg der Nierenretentionsparameter zu beobachten. Alle Nebenwirkungen waren reversibel. Es erfolgte kein vorzeitiger Therapieabbruch. Ein frühzeitiges Therapieansprechen (early virologic response, EVR) mit einem Abfall der Viruslast unter die Nachweisgrenze zu Woche 4 war bei 9/13 Patienten zu beobachten. Bei weiteren 3 Patienten fiel die HCV-RNA zu Woche 12 unter die Nachweisgrenze.

Folgerung: Unsere Ergebnisse zeigen eine hohe EVR-Rate unter TVR-basierter Triple-Therapie bei LTx-Patienten mit HCV-GT1-Reinfektion.

Abstract

Background and objective: The management of hepatitis C virus (HCV) recurrence after liver transplantation (LTx) is a major challenge in patient care. For patients with HCV GT1, treatment standard with pegylated interferon (PEG-IFN) and ribavirin (RBV) has been augmented in 2011 by first generation protease inhibitors (PI), telaprevir (TVR) and boceprevir (BOC). We report our first experiences with TVR-based triple therapy in patients with GT1-reinfection of the graft.

Patients and method: 13 patients with histologically proven HCV GT1-reinfection of the graft received 12 weeks of PEG-IFN/RBV/TVR followed by 12 weeks of PEG-IFN/ RBV only. During the triple therapy phase immune suppression was tightly monitored, and the patients were also closely monitored for side effects.

Results: The dosage of immunosuppressants had to be reduced significantly (TAC: 30-fold; CSA 3,5-fold). Stable levels were achieved by daily or over-daily dosing of a special size application of 0,1 mg tacrolimus (Tac) bid or a minimal dose of 10 mg cyclosporine (CSA) bid or qd, respectively. In all patients hematological side effects were observed, 65 % of which required RBV dose reduction, administration of erythropoietin or blood transfusions. Increase of kidney retention values requiring infusions occurred in 50 %. All side effects were reversible. There were no early discontinuations of therapy. An early viral response (EVR) with viral decline below limit of detection was noted at week 12 in 9/13 patients and at week 12 in further 3 patients.

Conclusion: Our preliminary results show high EVR response rates of TVR-based triple therapy in LTx patients with HCV-GT1 re-infection.

Schlüsselwörter

HCV-Infektion - Hepatitis C - Lebertransplantation - Triple-Therapie

Keywords

HCV infection - hepatitis C - liver transplantation - triple therapy

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