Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2024 Jul;22(7):1444-1452.e4.
doi: 10.1016/j.cgh.2024.02.006. Epub 2024 Feb 23.

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

Michael Li  1 , Danny Wong  2 , Jordan S Sack  2 , Alexander S Vogel  2 , F Stephen Hodi  3 , Lawrence Fong  4 , Jennifer C Lai  5 , Stephen D Zucker  2 , Shilpa Grover  2
Affiliations
Multicenter Study

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

Michael Li et al. Clin Gastroenterol Hepatol. 2024 Jul.

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.. Kaplan-Meier curves, stratified by hospitalization status.
A: Time to ALT normalization (ALT ≤40 U/L) B: Time to ALT improvement to ≤100 U/L
Figure 2.
Figure 2.. Love Plot evaluating covariate balance after inverse probability of treatment weighting
Figure 3.
Figure 3.. Kaplan-Meier curve, time to all-cause death in melanoma subgroup stratified by hospitalization status.
See this image and copyright information in PMC

References

    1. Michot JM, Bigenwald C, Champiat S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. Feb 2016;54:139–148. doi: 10.1016/j.ejca.2015.11.016 - DOI - PubMed
    1. Brahmer JR, Lacchetti C, Schneider BJ, et al. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. June 2018;36(17):1714–1768. doi: 10.1200/JCO.2017.77.6385 - DOI - PMC - PubMed
    1. Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. October 2018;29(Suppl 4):iv264–iv266. doi: 10.1093/annonc/mdy162 - DOI - PubMed
    1. Ahern E, Allen MJ, Schmidt A, Lwin Z, Hughes BGM. Retrospective analysis of hospital admissions due to immune checkpoint inhibitor-induced immune-related adverse events (irAE). Asia Pac J Clin Oncol. Jun 2020;doi: 10.1111/ajco.13350 - DOI - PubMed
    1. Nice L, Bycroft R, Wu X, et al. Assessment of hospitalization rates for immune-related adverse events with immune checkpoint inhibitors. J Oncol Pharm Pract. Oct 2021;27(7):1736–1742. doi: 10.1177/1078155220968909 - DOI - PubMed

Publication types

Substances