Immune checkpoint inhibitor-induced hepatitis injury: risk factors, outcomes, and impact on survival

Miah, Abdul; Tinoco, Gabriel; Zhao, Songzhu; Wei, Lai; Johns, Andrew; Patel, Sandip Pravin; Li, Mingjia; Grogan, Madison; Lopez, Gabrielle; Husain, Marium; Hoyd, Rebecca; Mumtaz, Khalid; Bertino, Erin M.; Kendra, Kari; Spakowicz, Daniel; Presley, Carolyn J.; Owen, Dwight H.

doi:10.1007/s00432-022-04340-3

Cited by 11 publications

(15 citation statements)

References 37 publications

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“…A significant positive correlation has been found between the occurrence of irLI and OS duration, with a median OS of 37.0 months in those who suffered irLI compared with 11.3 months in patients who did not 18 . However, there was no significant difference between the OS duration of grade ≥3 and grade 1–2 irLI patients 18 . In the present study, we found no significant improvement in the prognoses of patients with grade ≥3 irLI (Figure 2).…”

Section: Discussionmentioning

confidence: 91%

“…Thus, it is also important to ensure the correct grading of the irAE. A significant positive correlation has been found between the occurrence of irLI and OS duration, with a median OS of 37.0 months in those who suffered irLI compared with 11.3 months in patients who did not 18 . However, there was no significant difference between the OS duration of grade ≥3 and grade 1–2 irLI patients 18 .…”

Section: Discussionmentioning

confidence: 92%

“…18 However, there was no significant difference between the OS duration of grade ≥3 and grade 1-2 irLI patients. 18 In the present study, we found no significant improvement in the prognoses of patients with grade ≥3 irLI (Figure 2). This may be because grade ≥4 irAEs can inflict critical damage.…”

Section: Main Findingsmentioning

confidence: 89%

“…Several irLI mechanisms have been proposed, including the blocking of immune tolerance 14 ; the activity of CD8 + cytotoxic T lymphocytes, various CD4 + T‐cell populations, or cytokines; and secondary activation of the innate immune system 13 . Although the occurrence of irAEs is broadly associated with survival in cancer patients treated with ICI, 15–17 few studies have evaluated the risk factors or impact on OS of irLI 6,18 …”

Section: Introductionmentioning

confidence: 99%

“…13 Although the occurrence of irAEs is broadly associated with survival in cancer patients treated with ICI, [15][16][17] few studies have evaluated the risk factors or impact on OS of irLI. 6,18 In the present study, we aimed to identify factors associated with irLI, and the relationship between AE grades and OS in advanced cancer patients treated with ICIs. Furthermore, we investigated whether baseline LI (as determined by liver enzyme elevation) due to a background liver disease affects the safety of ICI treatment.…”

Section: Introductionmentioning

confidence: 99%

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

Kaneko

Asahina

Nakagawa

et al. 2023

Hepatology Research

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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.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 92%