Pembrolizumab-induced acute exacerbation of hepatitis D

Abstract

A 55-year-old man was treated with combined immunochemotherapy (pembrolizumab, carboplatin and pemetrexed) because of non-small cell lung cancer (NSCLC). In addition, the patient had a medical history of chronic hepatitis B/D virus infection and cystic echinococosis. The viral hepatitis co-infection was treated with pegylated interferon (IFN)-alpha and tenofovir in the past (non-response after treatment), followed by maintenance therapy with tenofovir. Since the echinococosis was inactive, there was no need for specific treatment. The therapy for NSCLC had to be stopped after three weeks due to rising liver enzymes. HDV-RNA could be detected as high as 10⁷ GE/mL in the serum, HBV-DNA was not detected. A liver biopsy was performed. Histological analysis showed a chronic and partly active hepatitis, but its aetiology remained unclear. Because of the stable viral load after the first administration of pembrolizumab, an autoimmune-induced liver injury was suspected. Thus, a prednisolone-treatment was initiated. Yet, the liver enzyme levels did not decline, so bulevirtide (2 mg/d s.c.) was added to the ongoing antiviral treatment with tenofovir. This new treatment combination led to a restitution of the elevated enzymes; HDV-RNA was below detection limit. Finally, the therapy for NSCLC could be continued. The antiviral therapy could improve the patient´s prognosis significantly. To our knowledge, this is the first reported case of a pembrolizumab-induced exacerbation of hepatitis D and a successful management by application of bulevirtide in the context of cancer.

Zusammenfassung

Ein 55-jähriger Patient wurde aufgrund eines nicht kleinzelligen Lungenkarzinoms (NSCLC) mit einer kombinierten Immunchemotherapie (Pembrolizumab, Carboplatin und Pemetrexed) behandelt. Anamnestisch waren zudem eine chronische Hepatitis B/D sowie eine zystische Echinokokkose bekannt. Die Hepatitis B/D-Koinfektion war zuvor mit pegyliertem Interferon (IFN)-alpha und anschließender Tenofovir-Erhaltungstherapie behandelt worden. Da die Echinokokkose inaktiv war, bedurfte es keiner spezifischen Behandlung. Aufgrund steigender Leberenzymwerte musste die Therapie des NSCLC unterbrochen werden. HDV-RNA wurde in Höhe von 10⁷ GÄ/ml im Serum nachgewiesen, HBV-RNA lag nicht vor. Anhand einer Leberbiopsie fanden sich histologisch Zeichen einer teils chronischen, teils akuten Hepatitis. Dabei blieb die Ätiologie weiterhin unklar. Da die HDV-Viruslast nach der Erstgabe von Pembrolizumab stabil war, wurde eine autoimmun-bedingte Leberschädigung angenommen. Daher wurde eine Prednisolon-Therapie eingeleitet. Hierunter sanken die erhöhten Leberenzymwerte jedoch nicht, sodass die bestehende antivirale Therapie mit Tenofovir um Bulevirtid (2 mg tägl. s.c.) ergänzt wurde. Diese neue Therapiekombination führte zu einer Normalisierung der Leberwerte; HDV-RNA sank unter die Nachweisgrenze. Schließlich konnte die Therapie des NSCLC fortgeführt werden. Die antivirale Therapie konnte die Prognose des Patienten signifikant verbessern. Nach unserem Kenntnisstand ist dies der erste berichtete Fall einer Pembrolizumab-induzierten Exazerbation einer Hepatitis D einschließlich der erfolgreichen Therapie mit Bulevirtid im onkologischen Kontext.

Schlüsselwörter

Leber - Virushepatitis - Hepatitis D

Keywords

liver - viral hepatitis - hepatitis D

Publication History

Received: 19 June 2022

Accepted after revision: 29 August 2022

Article published online:
14 November 2022

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