LIVER INJURY IN HOSPITALIZED COVID-19 PATIENTS TREATED WITH TOCILIZUMAB

ABSTRACT

Background: Tocilizumab is a humanized monoclonal antibody that targets Interleukin-6 receptors. Recent trials have shown that tocilizumab may be effective against COVID-19. It is also known that tocilizumab may be associated with mild aminotransferase elevation, however, there are very limited data on hepatotoxicity of tocilizumab in patients with COVID- 19. Here we report our institutional experience on the development of liver injury after tocilizumab use in hospitalized patients with COVID-19. Methods: We analyzed all consecutive adult hospitalized patients who had PCR confirmed COVID-19 and were admitted to our hospital network between January 1st, 2021, and November 15th, 2021. To be considered eligible for inclusion patients should had an admission liver injury panel and at least one additional follow-up panel before discharge. Patients with baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times of the upper normal limit were excluded. Liver injury was measured by ALT, AST, or total bilirubin elevation. Grading was based on the Common Terminology Criteria for Adverse Events version 5.0. The primary outcome of interest was to estimate the incidence of liver injury among patients who received tocilizumab. As a secondary outcome, we examined the association of all-grade liver injury with tocilizumab use by utilizing a multivariate logistic regression model adjusted for demographics, comorbidities, Remdesivir use, and baseline COVID-19 severity based on the NEWS score. Results: Among 1409 consecutive hospitalized patients who met the inclusion criteria, we identified 87 patients who received tocilizumab. Baseline patient characteristics are depicted on Table 1. We found that the incidence of any grade AST elevation was higher in the tocilizumab versus non-tocilizumab group (24.1% vs 13%;p=0.015), with similar findings in ALT (32.1% vs 18%;p=0.016) and bilirubin (18% vs 4.5% p<0.001) (Table 2). Likewise, in our multivariate logistic regression model, patients who received tocilizumab were more likely to have had elevated ALT (OR 2.16;95% CI 1.31-3.55), AST (OR 2.56;95% CI 1.48-4.43), or bilirubin (OR 3.30;95% CI 1.57-6.92), compared to those who did not receive the drug. Conclusion: While tocilizumab is frequently utilized in the treatment of COVID-19 patients, few studies have evaluated its hepatotoxic potential in this population. Based on our institutional experience, tocilizumab use in hospitalized patients with COVID-19 is associated with ALT, AST, and bilirubin elevation even after adjusting for COVID-19 severity. However, the majority of hepatic injury events were graded as level I (mild injury) and severe hepatotoxicity was rare. Further studies are needed to confirm these findings, while monitoring of hepatic function after tocilizumab use is warranted, especially in patients with chronic liver disease. (Table Presented)