Factors associated with liver injury and prognosis in advanced cancer patients treated with immune checkpoint inhibitors

Shun Kaneko; Yasuhiro Asahina; Mina Nakagawa; Miyako Murakawa; Yasunari Miyazaki; Takahiro Asakage; Shohei Fukuda; Takeshi Namiki; Yoshihito Kano; Masashi Nagata; Jun Tsuchiya; Masato Miyoshi; Fukiko Kitahata-Kawai; Sayuri Nitta; Yasuhiro Itsui; Sei Kakinuma; Ryuichi Okamoto

doi:10.1111/hepr.13878

Factors associated with liver injury and prognosis in advanced cancer patients treated with immune checkpoint inhibitors

Hepatol Res. 2023 May;53(5):450-459. doi: 10.1111/hepr.13878. Epub 2023 Jan 27.

Authors

Shun Kaneko¹, Yasuhiro Asahina^{1

2}, Mina Nakagawa¹, Miyako Murakawa¹, Yasunari Miyazaki³, Takahiro Asakage⁴, Shohei Fukuda⁵, Takeshi Namiki⁶, Yoshihito Kano⁷, Masashi Nagata⁸, Jun Tsuchiya¹, Masato Miyoshi¹, Fukiko Kitahata-Kawai¹, Sayuri Nitta¹, Yasuhiro Itsui¹, Sei Kakinuma¹, Ryuichi Okamoto¹

Affiliations

¹ Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
² Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan.
³ Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
⁴ Department of Head and Neck Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
⁵ Department of Urology, Tokyo Medical and Dental University, Tokyo, Japan.
⁶ Department of Dermatology, Tokyo Medical and Dental University, Tokyo, Japan.
⁷ Department of Clinical Oncology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
⁸ Department of Pharmacy, Tokyo Medical and Dental University, Tokyo, Japan.

PMID: 36626292
DOI: 10.1111/hepr.13878

Abstract

Aim: The use of immune checkpoint inhibitors (ICIs) has increased remarkably, and immune-related adverse events (irAEs) have also increased. This study aimed to identify factors associated with immune-related liver injury (irLI), and the relationship between the grades of irLI and overall survival (OS) in patients treated with ICIs.

Methods: A total of 571 patients who had been treated for advanced malignancies with ICIs between January 2015 and March 2022 were retrospectively recruited. The presence of liver injury was determined by the aspartate aminotransferase and alanine aminotransferase elevation. The irLI grading was based on Common Terminology Criteria for Adverse Events version 5.0.

Results: A total of 50 (8.8%) patients had grade ≥2 irLI and 24 (4.2%) had grade ≥3 irLI. Treatment with anti-cytotoxic T-lymphocyte-associated protein-4 agents and baseline grade 1 aspartate aminotransferase/alanine aminotransferase elevation were independent predictive factors of grade ≥2 irLI. Treatment with anti-cytotoxic T-lymphocyte-associated protein-4 was the only independent predictive factor of grade ≥3 irLI. The median OS for patients who experienced any irAEs was significantly longer than of those without irAEs (hazard ratio 0.503, 95% CI 0.398-0.636, p < 0.001). The median OS in patients with grade ≥2 irLI was significantly longer (HR 0.570, 95% CI 0.387-0.838, p = 0.022). There was no significant difference between the median OS in patients with grade ≥3 irLI and the others (p = 0.11).

Conclusion: The incidence of irLI was significantly higher in patients treated with anti-cytotoxic T-lymphocyte-associated protein-4 agents. Even in patients with pre-existing grade 1 aspartate aminotransferase/alanine aminotransferase elevation, appropriate follow-up and control of the irLI can improve the prognosis.

Keywords: cytotoxic T-lymphocyte-associated protein-4; immune checkpoint inhibitors; immune-related adverse events; liver injury; programmed death receptor-1; programmed death-ligand 1.

Grants and funding

None