Hepatotoxicity associated with acute tocilizumab treatment in patients with sarscov-2 infection

ABSTRACT

Background and importance Tocilizumab (TCZ) has been proposed to mitigate the cytokine storm syndrome associated with SARS-CoV-2. However, acute administration of this drug has been shown to cause serious adverse effects at the level of the liver, including acute liver failure. Aim and objectives To evaluate the liver toxicity profile associated with the acute use of TCZ in patients with SARS-CoV-2 infection. Material and methods A retrospective single centre study, lasting 2 months (March to April 2020), was conducted in all patients with a clinical suspicion/diagnosis confirmed of SARSCoV-2 infection and who had received treatment with TCZ. The following variables were collected age, sex, posology scheme of TCZ, admission to the intensive care unit (ICU), need for orotracheal intubation (OTI) and death during the hospital stay. The hepatic profile was analysed for levels of hepatic transaminases (GOT/AST and GPT/ALT) and total bilirubin (TOT BL) pre and post completion of treatment with TCZ. Alteration of liver parameters was classified as mild (1- 3 × upper limit of normality (UPN)), moderate (3-5 × UPN) and severe (≥5 × UPN). Results During the study period, 44 patients with SARS-CoV-2 infection were treated with TCZ (65.9% men (n=29);mean age 62.3 years (31-82)). The posology scheme of TCZ used was the following single dose (68.2%, n=30), double dose (18.2%, n=8) and triple dose (11.6%, n=6). Two patients (4.5%) received a 50% reduced dose because of previous liver failure. During admission, 56.8% (n=25) of patients required a stay in the ICU. 36.4% (n=16) needed OTI. 9.1% (n=4) died during admission. Liver profile analysis showed that 72.7% of patients (n=32) presented with normal levels of GPT/ALT and GOT/AST before treatment. 59.1% (n=26) presented with normal levels of BL TOT and 4.5% (n=2) had high levels. In 34.1% (n=15) there were no data. After treatment with TCZ, 86.3% (n=38) developed hepatotoxicity. Elevation of GPT/ALT was observed mild (42.1%), moderate (28.9%) and severe (28.9%);elevation of GOT/AST mild (44.7%), moderate (31.6%) and severe (13.2%). 42.9% (n=12) presented with high levels of BL TOT after receiving TCZ. Conclusion and relevance The study showed how a high proportion of patients with SARS-CoV-2 infection developed severe liver toxicity after the use of the drug. However, future studies will be needed to clarify the involvement of SARSCoV-2 itself in the development of hepatotoxicity.