Incidence rate and treatment strategy of immune checkpoint inhibitor mediated hepatotoxicity: A systematic review

Abstract

Background

A hepatic adverse event (HAE) is defined as a liver injury that occurs following immune checkpoint inhibitor (ICI) administration in oncology Patients. Immune-mediated hepatotoxicity (IMH) is a type of HAE directly caused by ICI and is associated with immune system hyperactivation. HAE incidence varies across different clinical studies. This study aimed to explore the risk factors of HAE and establish a personalized IMH treatment strategy.

Methods

Randomized controlled trials (RCTs) on ICIs and case reports related to IMH were collected and summarized separately. Meta-analysis was performed using Review Manager (version 5.0), whereas correlation analysis and linear regression were performed using SPSS (version 24.0) to evaluate any correlations between the two variables.

Results

Overall, 36 RCTs containing 18,515 patients and 39 case reports met our inclusion criteria. The ICI administration increased the HAE risk (risk ratio [RR] ​= ​1.40) as well as severe HAE (RR ​= ​2.55). The overall HAE incidence and severe incidence were about 15.3% and 4.3%, respectively. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors have a higher incidence of HAE than programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. Finally, we found a positive correlation between the onset time of IMH and the recovery time of liver injury.

Conclusions

ICI administration increased the incidence risk of HAE, especially in patients treated with CTLA-4 inhibitors. Regarding IMH treatment, the glucocorticoid dosage must be individually reduced according to the severity and onset time of HAE.