Pembrolizumab-induced acute exacerbation of hepatitis D

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.