Outcomes of High-Grade Immune Checkpoint Inhibitor Hepatitis in Hospitalized and Nonhospitalized Patients

Michael Li; Danny Wong; Jordan S Sack; Alexander S Vogel; F Stephen Hodi; Lawrence Fong; Jennifer C Lai; Stephen D Zucker; Shilpa Grover

doi:10.1016/j.cgh.2024.02.006

Outcomes of High-Grade Immune Checkpoint Inhibitor Hepatitis in Hospitalized and Nonhospitalized Patients

Clin Gastroenterol Hepatol. 2024 Feb 23:S1542-3565(24)00210-6. doi: 10.1016/j.cgh.2024.02.006. Online ahead of print.

Authors

Michael Li¹, Danny Wong², Jordan S Sack², Alexander S Vogel², F Stephen Hodi³, Lawrence Fong⁴, Jennifer C Lai⁵, Stephen D Zucker², Shilpa Grover²

Affiliations

¹ Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, California. Electronic address: michael.li@ucsf.edu.
² Division of Gastroenterology, Hepatology, and Endoscopy, Brigham & Women's Hospital, Boston, Massachusetts.
³ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
⁴ Division of Hematology/Oncology, University of California, San Francisco, San Francisco, California.
⁵ Division of Gastroenterology and Hepatology, University of California, San Francisco, San Francisco, California.

PMID: 38401693
DOI: 10.1016/j.cgh.2024.02.006

Abstract

Background & aims: Guidelines recommend hospitalization for severe immune checkpoint inhibitor (ICI) hepatitis. We compared patient outcomes in the inpatient versus outpatient settings.

Methods: We conducted a multicenter, retrospective cohort study of 294 ICI-treated patients who developed grade 3-4 ICI hepatitis. The primary outcome was time to alanine aminotransferase (ALT) normalization (≤40); secondary outcomes included time to ALT ≤100 U/L and time to death. To account for confounding by indication, inverse probability of treatment weighting was applied to perform Cox regression. A sensitivity analysis was performed excluding patients with grade 4 hepatitis.

Results: One hundred and sixty-six patients (56.5%) were hospitalized for a median of 6 (interquartile range, 3-11) days. On inverse probability of treatment weighting Cox regression, hospitalization was not associated with time to ALT normalization (hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.86-1.43; P = .436) or time to ALT ≤100 U/L (HR, 1.11; 95% CI, 0.86-1.43; P = .420). In the sensitivity analysis limited to patients with grade 3 hepatitis, hospitalization was also not associated with time to ALT normalization (HR, 1.11; 95% CI, 0.83-1.50; P = .474) or time to ALT ≤100 U/L (HR, 1.19; 95% CI, 0.90-1.58; P = .225). In a subgroup analysis of 152 patients with melanoma, hospitalization was not associated with reduced risk of all-cause death (HR, 0.93; 95% CI, 0.53-1.64; P = .798). Notably, despite their Common Terminology Criteria for Adverse Events classification of high-grade hepatitis, 94% of patients had "mild" liver injury based on International Drug-Induced Liver Injury Criteria.

Conclusions: Hospitalization of patients with high-grade ICI hepatitis was not associated with faster hepatitis resolution and did not affect mortality. Routine hospitalization may not be necessary in all patients with high-grade ICI hepatitis and Common Terminology Criteria for Adverse Events criteria may overestimate severity of liver injury.

Keywords: Drug-Induced Liver Injury; Immune-Related Adverse Event; Immunotherapy.