Elevated tocilizumab-induced transaminase levels during treatment for severe SARS-CoV-2 infection: Meta-analytical study

Abstract

Objective: systematic study of increased levels of tocilizumab-induced hepatic transaminases (TCZ) in patients with SARS-CoV-2 infection. Material and methods:We searched PubMed, EMBASE and Google Scholar for studies published between January 2020 and August 2021.We included studies reporting data with levels of hepatic transaminases (aspartate aminotransferase or AST and alanine aminotransferase or ALT) in patients infected with SARS-CoV-2 on treatment with TCZ, either in case-control studies or when these levels are measured before and after therapy in the same patient.The quality of the articles was evaluated according to the Newcastle Ottawa (NOS) scale. Data were extracted on study design, country, number of patients, age and sex. A random effects model was applied for the construction of the tree diagram based on the delta of the mean and standard deviation of the ALT and GPT levels of the cases and control, from each of the included reports, with a 95% confidence interval (CI). Results:We identified 5 case-control studies for inclusion, totaling a total of 511 patients.The mean age was 62,3 + 5,0 years and 78,8% were male.The mean NOS score of the included studies was 7,8 + 0,4.The dose used of TCZ was 8mg/kg/day. In the tree diagram it was observed that the delta of the mean variation of alt and AST were 0,33 (delta 95% confidence interval: 0,17-0,5; I2 = 73% p<0,05) and 0,34 (95% CI: 0,17-0,51; I2 =84% p<0,05), respectively. In one study, normalization of ALT and AST was reported at the 3rd week, and the rest of the studies did not report evolution data. Conclusion:The use of TCZ in SARS-CoV-2 infection is associated with elevation of ALT and AST, however, its levels do not meet criteria for drug-induced liver injury and is apparently self-limiting. Further studies are required to confirm the temporal nature of the transaminase elevation associated with TCZ.