Prophylaxe und Therapie der Reaktivierung einer Hepatitis B bei Immunsuppression

Zusammenfassung

Die chronische Hepatitis-B-Virus (HBV)-Infektion kann niedrig-replikativ mit günstiger Prognose oder hoch-replikativ mit dem Risiko einer Leberzirrhose und eines Leberzellkarzinoms verlaufen. Eine Immunsuppression im Rahmen einer lokalen oder systemischen Chemotherapie sowie einer autoimmunen Krankheit erhöht signifikant das Risiko der Reaktivierung einer HBV, zum Teil mit dem Bild einer akuten, selten fulminanten Hepatitis. Unter intensiver Immunsuppression z. B. im Rahmen einer Stammzelltransplantation kann eine Re-Serokonversion auftreten mit Verlust von anti-HBs +/– anti-HBc und erneutem Nachweis von HBsAg sowie HBV-DNA und dem Risiko einer akuten (fulminanten) Hepatitis. Bestimmte Chemotherapeutika und Immunsuppressiva begünstigen eine Reaktivierung. In Studien konnte gezeigt werden, dass die Reaktivierung einer Hepatitis B Virusinfektion erfolgreich mit dem Nukleosidanalogon Lamivudin behandelt werden kann, eine prophylaktische Gabe scheint der Therapie einer Re-Aktivierung überlegen zu sein. Für weitere Nukleosid- (Telbivudin, Entecavir) oder Nukleotidanloga (Adefovir, Tenofovir) liegen bislang keine größeren Erfahrungen in dieser Indikation vor. Bei allen Patienten vor einer immunsuppressiven Therapie muss daher der HBV Serostatus geprüft werden. Patienten ohne HBV Infektion und ohne ausreichenden anti-HBs-Titer müssen aktiv immunisiert werden. Bei Patienten mit chronischer HBV Infektion und hochdosierter Immunsuppression besteht gemäß der aktuellen Leitlinie der DGVS die Indikation zur antiviralen Therapie. Bei Nachweis einer durchgemachten Hepatitis B Virusinfektion (anti-HBc positiv, HBsAg negativ) muss eine Kontrolle vor und regelmäßig unter immunsuppressiver Therapie sowie im Fall der Reaktivierung eine Therapie mit Nukleos(t)idanaloga erfolgen. Bei Patienten vor Stammzelltransplantation muss bereits bei Nachweis einer durchgemachten HBV Infektion eine Prophylaxe mit einem Nukleos(t)idanalogon eingeleitet werden.

Abstract

Immunosuppression because of local or systemic chemotherapy or immunosuppressive therapy of autoimmune diseases is an increasing risk for reactivation of hepatitis B and may lead to acute hepatitis and rarely to fulminant hepatitis. Intensive immunosuppression, e. g. in advance of bone marrow transplantation, may lead to re-seroconversion with loss of anti-HBs and detection of HBsAg and HBV-DNA and a risk of (fulminant) hepatitis. Distinct chemotherapeutics and immunosuppressive medication promote reactivation or re-seroconversion of HBV infection. Several studies have shown a significant benefit by antiviral therapy with nucleosidanalogue lamivudine to avoid reactivation. For other nucleoside analogues (telbivudine, entecavir) or nucleotide analogues (adefovir dipivoxil, tenofovir) larger experiences are yet missing in this situation. Prophylaxis with antiviral agents may be superior to therapy of reactivation. Prior to onset of immunosuppressive treatment patients must be tested for HBV. Patients without detection of HBsAg and without sufficient anti-HBs-titer should receive active immunisation. In case of chronic HBV infection antiviral therapy should be initiated before intense immunosuppression. In case of HBV infection in medical history (anti-HBc positive, HBsAg negative) HBV serostatus should be tested frequently. In case of reactivation, therapy with nucleos(t)ide analogue should immediately be initiated. In case of bone marrow transplantation prophylaxis with nucleos(t)idanalogue has to be initiated before onset of treatment if anti-HBc is detectable, independent from HBsAg result.

Schlüsselwörter

Hepatitis B Virus - Immunsuppression - Prophylaxe - Chemotherapie - TACE

Keywords

hepatitis B - immunosuppression - prophylaxis - chemotherapy - TACE

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