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Meta-Analysis
. 2024 Sep 18;8(10):e0525.
doi: 10.1097/HC9.0000000000000525. eCollection 2024 Oct 1.

Steroid-refractory immune checkpoint inhibitor (ICI) hepatitis and ICI rechallenge: A systematic review and meta-analysis

Soo Young Hwang  1   2 , Pinghsin Hsieh  1 , Wei Zhang  2
Affiliations
Meta-Analysis

Steroid-refractory immune checkpoint inhibitor (ICI) hepatitis and ICI rechallenge: A systematic review and meta-analysis

Soo Young Hwang et al. Hepatol Commun. .

Abstract

Background: In recent years, the use of immune checkpoint inhibitors (ICIs) has become a cornerstone in cancer treatment. However, this has also resulted in the emergence of immune-related adverse events, notably ICI hepatitis, posing a significant clinical challenge. While steroids are the primary treatment, there are increasing cases of steroid-refractory ICI hepatitis. Our objective is to investigate the management of ICI hepatitis and its response to steroid treatment.

Methods: PubMed/MEDLINE, EMBASE, and CENTRAL databases were searched in July 2023 based on keywords including ICIs (anti-Programmed cell death protein 1/Programmed Death-Ligand 1, anti-CTLA-4, and anti-LAG3) and hepatitis.

Results: A total of 4358 studies were screened, and 44 studies were included in this systematic review. One thousand eight hundred fifty-six patients with ICI hepatitis were included (grade 1-2: 31.7%, grade 3-4: 56.0%, and unknown: 12.3%) with 1184 patients who received corticosteroid treatment. The duration of treatment and dosage varied considerably across the studies. Mycophenolate mofetil was the predominant agent used in 68 out of 82 cases (82.9%), followed by infliximab and azathioprine. A summary estimate of the proportion of steroid-refractory hepatitis in a random effects model was 16% (95% CI: 11%-23%). An estimated 40% (95% CI: 30%-51%) of patients of all patients with ICI hepatitis were rechallenged with an ICI, and of those rechallenged, there was an estimated 22% (95% CI: 15%-30%) recurrence.

Conclusions: Corticosteroids are the primary treatment for ICI hepatitis, with mycophenolate mofetil used as a secondary option for steroids-refractory cases. Current practices mostly rely on expert consensus, highlighting the need for further research to validate and optimize these treatments, particularly for steroid-resistant cases.

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Conflict of interest statement

The authors have no conflicts to report.

Figures

FIGURE 1
FIGURE 1
Flow diagram of all included studies. *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools. From Page et al. For more information, visit: http://www.prisma-statement.org/.
FIGURE 2
FIGURE 2
Forest plot of the proportion of steroid-refractory ICI hepatitis. Abbreviation: ICI, immune checkpoint inhibitor.
FIGURE 3
FIGURE 3
(A) Proportion of patients who were rechallenged with an ICI. (B) Proportion of ICI recurrences in patients who were rechallenged. Abbreviation: ICI, immune checkpoint inhibitor.
See this image and copyright information in PMC

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