Liver Toxicity After the Use of Tocilizumab in COVID-19 Patient

Abstract

Although various treatment methods are used with current information in COVID-19 patients, there is no proven cure and the researchs for effective treatment continues worldwide. It has been shown that the effect of the inflammatory storm in the pathogenesis of COVID-19 causes gas exchange dysfunction between the alveoli and blood vessels, which subsequently leads to pulmonary fibrosis and organ failure. Interleukin-6 (IL-6) plays a key role in this pathogenesis. Tocilizumab (TCZ) is a recombinant human monoclonal antibody that acts as an IL-6 receptor antagonist. There are studies on tocilizumab treatment showing that it significantly reduces the cytokine storm in which IL-6 plays an important role and the infiltration of inflammatory cells into the lung. In this article; a case of liver toxicity developed after tocilizumab treatment, who was followed up in the intensive care unit due to severe COVID-19 disease, is presented.

Keywords

• Tocilizumab
• Liver Toxicity
• COVID-19
• SARS-CoV-2

COVID-19 Hastasında Tosilizumab Kullanımı Sonrası Gelişen Karaciğer Toksisitesi

Abstract

COVID-19 hastalarında mevcut bilgilerle çeşitli tedavi yöntemleri uygulansa da, kanıtlanmış kesin bir tedavisi bulunmamakta ve dünya çapında etkin tedavi arayışı devam etmektedir. COVID-19 patogenezinde inflamatuar fırtınanın yarattığı etkinin alveol ile kan damarları arasındaki gaz değişim disfonksiyonuna neden olduğu, sonrasında pulmoner fibrozis ve organ yetmezliğine yol açtığı gösterilmiştir. İnterlökin-6 (IL-6) bu patogenezde anahtar role sahiptir. Tosilizumab (TCZ), IL-6 reseptör antagonisti olarak işlev gören, rekombinant insan monoklonal antikorudur. Tosilizumab tedavisinin; IL-6’nın anahtar rol oynadığı sitokin fırtınasını ve inflamatuar hücrelerin akciğere infiltrasyonunu önemli ölçüde azalttığına dair çalışmalar mevcuttur. Bu yazıda; ağır seyirli COVID-19 hastalığından dolayı yoğun bakım ünitesinde takip edilen, tosilizumab tedavisi sonrasında gelişen karaciğer toksisitesi olgusu sunulmuştur.

Keywords

• Tosilizumab
• Karaciğer Toksisitesi
• COVID-19
• SARS-CoV-2

References

1. World Health Organization (WHO). WHO Coronavirus Disease (COVID-19) Dashboard. https://covid19.who.int. Erişim: 08.11.2020
2. Uğuz M, Eşkut B. Covid-19 Enfeksiyon Tedavisi. Medical Research Reports. 2020; 3 (Supp 1):17-31.
3. Zhou Y, Fu B, Zheng X, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+ CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. BioRxiv. 2020: 2020.02.12.945576. DOI: https://doi.org/10.1101/2020.02.12.945576.
4. Giamarellos-Bourboulis EJ, Netea MG, Rovina N, et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe. 2020:S1931-3128(20)30236-5. DOI:10.1016/j.chom.2020.04.009.
5. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the chinese center for disease control and prevention. JAMA. 2020;323(13):1239.
6. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020; 395(10223): 507-513. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395:497-506.
7. National Health Commission & State Administration of Traditional Chinese Medicine. Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7). 2020. http://www.kankyokansen.org/uploads/uploads/files/jsipc/protocol_V7.pdf. Erişim: 08.11.2020
8. Türkiye Cumhuriyeti Sağlık Bakanlığı. COVID-19 Hastalarında Antisitokin-Antiinflamatuar Tedaviler, Koagülopati Yönetimi. 2020. https://covid19.saglik.gov.tr/ Eklenti/39296/0/covid-19rehberiantisitokin-antiinflamatuartedavilerkoagulopati yonetimipdf.pdf. Erişim: 08.11.2020

9. Xu X, Han M, Li T, et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA. 2020; 117(20):10970-10975.
10. Di Giambenedetto S, Ciccullo A, Borghetti A, et al. Off-label use of tocilizumab in patients with SARS-CoV-2 infection. J Med Virol. 2020: 25897. doi:10.1002/jmv.25897.
11. Sheppard M, Laskou F, Stapleton PP, Hadavi S, Dasgupta B. Tocilizumab (Actemra). Hum Vaccin Immunother. 2017;13(9): 1972- 1988.
12. Muhović D, Bojović J, Bulatović A, Vukčević B, Ratković M, Lazović R, Smolović B. First case of drug-induced liver injury associated with the use of tocilizumab in a patient with COVID-19. Liver Int. 2020;40(8):1901-1905. doi: 10.1111/liv.14516.