Acute acalculous cholecystitis following extended administration of nirmatrelvir/ritonavir for persistent SARS-CoV-2 infection

Wataru Ito; Tatsuya Fukumori; Nao Asaoka; Natsuko Imakita; Tomoko Nishimura; Ryutaro Furukawa; Yuji Nishihara; Hiroyuki Fujikura; Takahiro Sekine; Naoki Yamaguchi; Yuichiro Hirata; Sho Miyamoto; Takayuki Kanno; Harutaka Katano; Tadaki Suzuki; Kei Kasahara

doi:10.1016/j.jiac.2023.12.014

Acute acalculous cholecystitis following extended administration of nirmatrelvir/ritonavir for persistent SARS-CoV-2 infection

J Infect Chemother. 2024 Jan 5:S1341-321X(24)00001-1. doi: 10.1016/j.jiac.2023.12.014. Online ahead of print.

Authors

Affiliations

¹ Department of Infectious Diseases, Nara Medical University, Kashihara, Nara, Japan.
² Department of Intensive Care Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.
³ Department of Infectious Diseases, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Hyogo, Japan.
⁴ Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan.
⁵ Department of Infectious Diseases, Nara Medical University, Kashihara, Nara, Japan. Electronic address: kassan@naramed-u.ac.jp.

PMID: 38184107
DOI: 10.1016/j.jiac.2023.12.014

Abstract

Immunocompromised patients with hematologic malignancies, particularly those treated with anti-CD20 antibodies such as rituximab and obinutuzumab, are known to be at risk of prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prolonged administration or combination therapy with antiviral medications reportedly yields favorable outcomes in these patients. However, knowledge regarding the adverse events associated with such therapeutic approaches is limited. Herein, we report a case of acute acalculous cholecystitis (AAC) following extended administration of nirmatrelvir/ritonavir (NMV/r) in a 68-year-old Japanese man with persistent SARS-CoV-2 infection. The patient had received obinutuzumab and bendamustine for follicular lymphoma and was diagnosed with coronavirus disease 2019 (COVID-19) approximately one year after treatment initiation with these drugs. Subsequently, he was admitted to a different hospital, where he received antiviral drugs, monoclonal antibodies, and steroids. Despite these interventions, the patient relapsed and was subsequently transferred to our hospital due to persistent SARS-CoV-2 infection. Remdesivir administration was ineffective, leading to the initiation of extended NMV/r therapy. One week later, he exhibited elevated gamma-glutamyl transpeptidase (GGT) levels, and one month later, he developed AAC. Cholecystitis was successfully resolved via percutaneous transhepatic gallbladder drainage and administration of antibiotics. We speculate that extended NMV/r administration, in addition to COVID-19, may have contributed to the elevated GGT and AAC. During treatment of persistent SARS-CoV-2 infection with extended NMV/r therapy, patients should be carefully monitored for the appearance of findings suggestive of biliary stasis and the development of AAC.

Keywords: Acute acalculous cholecystitis; Gamma-glutamyl transpeptidase; Lymphoma; Nirmatrelvir/ritonavir; Obinutuzumab; Persistent SARS-CoV-2 infection.

Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.

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Case Reports