Hepatotoxicity Associated with Immune Checkpoint Inhibitors in Clinical Practice: A Study Leveraging Data from the US Food and Drug Administration's Adverse Event Reporting System

The ABC of Immune-Mediated Hepatitis during Immunotherapy in Patients with Cancer: From Pathogenesis to Multidisciplinary Management

“…Li and colleagues conducted a retrospective analysis of liver biopsy in a cohort of 213 patients who developed IMH. In this paper, patients with ICI hepatitis undergoing a liver biopsy showed longer median (IQR) time to ALT normalization (42 [6, vs. 33 [6,[27][28][29][30][31][32][33][34][35][36][37] days; p = 0.01) and to ALT levels of 100 U/L or less (21 [2,17-25] vs. 15 [14][15][16][17] days; p = 0.01). These data underline that performing a liver biopsy in this setting may delay the initiation of corticosteroids and in the resolution of liver inflammation [49].…”

“…Recently, a pharmacovigilance study based on data from the FAERS database has analyzed 1481 reports of immune-mediated liver toxicity. The authors have demonstrated that ICIs are significantly associated with liver failure (IC = 1.24, 95% CI, 1.06-1.42) and that ICI combination therapy presents a greater risk compared to ICI monotherapy [14].…”

“…The reported incidence of immune-mediated hepatotoxicity (IMH) varies according to the class of ICI, the type of tumors, and underlying clinical conditions. In the abovementioned pharmacovigilance study, the authors highlighted that anti-PD-L1 treatment has a risk of 1.20-fold and 1.31-fold greater than those with anti-CTLA-4 and anti-PD-1 treatments, respectively [14]. This observation is in contrast with a meta-analysis of 17 clinical trials that described a higher risk of hepatotoxicity in the case of treatment with anti-CTLA-4 than with anti-PD-1 (odds ratio [OR] for high-grade hepatoxicity = 1.52 vs. 0.48) [15].…”

“…The incidence of liver toxicity with anti-CTLA-4 monotherapy ranges from 2% to 15%, while with anti-PD-1 and anti-PD-L1 it ranges from 0% to 3% and 0% to 6%, respectively [16]. ICI combination therapy showed a greater rate of hepatotoxicity compared with ICI monotherapy (IC = 0.63, 95% CI, 0.99-2.04; ROR = 1.31 [95% CI, 1.80-2.31]) [14]. In the phase III clinical trial Checkmate 067, patients with advanced melanoma treated with ipilimumab plus nivolumab presented a higher alanine aminotransferase (ALT) increase (19%) when compared to those receiving ipilimumab (4%) or nivolumab (4%), while the increase in aspartate aminotransferase (AST) was 17%, 4%, and 4%, respectively [17].…”

Severe and fatal adverse events of immune checkpoint inhibitor combination therapy in patients with metastatic renal cell carcinoma: a systematic review and meta-analysis

“…Wang et al. ( 30 ) reported that using ICIs was associated with greater hepatotoxicity than all other systematic treatments and that ICI combination therapy had a greater risk of hepatotoxicity (including hepatic failure) than ICI monotherapy. Because of the significant association between ICI-based therapy and hepatotoxicity, clinicians should focus more attention on this safety signal.…”