Risk Factors of Immune-Mediated Hepatotoxicity Induced by Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis

Immune checkpoint inhibitors (ICIs) significantly improve survival, while immune-mediated hepatotoxicity (IMH) has been reported. To evaluate the incidence and potential risk factors of IMH among cancer patients treated by ICIs, PubMed/Medline, Web of Science, Cochrane, and Embase were searched befo...

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Main Authors: Ying Jiang, Ranyi Li, Xiaoyu Li, Ningping Zhang
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Current Oncology
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Online Access:https://www.mdpi.com/1718-7729/31/11/525
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author Ying Jiang
Ranyi Li
Xiaoyu Li
Ningping Zhang
author_facet Ying Jiang
Ranyi Li
Xiaoyu Li
Ningping Zhang
author_sort Ying Jiang
collection DOAJ
description Immune checkpoint inhibitors (ICIs) significantly improve survival, while immune-mediated hepatotoxicity (IMH) has been reported. To evaluate the incidence and potential risk factors of IMH among cancer patients treated by ICIs, PubMed/Medline, Web of Science, Cochrane, and Embase were searched before 30 March 2024 for systematic review and meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated. Quality assessment was completed using the Newcastle–Ottawa scale. Of 1217 articles identified, 24 consisting of 9076 patients were included, with one study being prospective and the rest retrospective. The overall incidence of any grade IMH and grade ≥ 3 secondary to ICIs was 14% and 7%, respectively. The cholestatic pattern was more prevalent than the hepatocellular and mixed patterns. The meta-analysis revealed that ICI treatment was related to reduced risk of IMH in older patients (SMD: −0.18; 95% CI: −0.33 to −0.04), individuals with higher body mass index (WMD: −2.15; 95% CI: −3.92 to −0.38), males (OR: 0.44; 95% CI: 0.27 to 0.72), and patients with lung cancer (OR: 0.58, 95%CI 0.41 to 0.83). On the other hand, patients with liver metastasis (OR: 1.80; 95% CI: 1.47 to 2.20), history of ICI treatment (OR: 3.09; 95% CI: 1.21 to 7.89), diabetes (OR: 2.19; 95% CI: 1.36 to 3.51), chronic HBV (OR: 3.06; 95% CI: 1.11 to 8.46), and concomitant use of ICIs (OR: 8.73; 95% CI: 2.41 to 31.59) increased the risk of developing IMH. This study will provide clinicians with information on potentially high-risk groups for IMH, who need to be cautiously monitored for liver function when receiving immunotherapy.
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spelling doaj-art-28fc9df6ba7b4604893fe4fe2cb147ca2025-08-20T02:28:04ZengMDPI AGCurrent Oncology1198-00521718-77292024-11-0131117129714310.3390/curroncol31110525Risk Factors of Immune-Mediated Hepatotoxicity Induced by Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-AnalysisYing Jiang0Ranyi Li1Xiaoyu Li2Ningping Zhang3Department of Pharmacy, Zhongshan Hospital Fudan University, Shanghai 200032, ChinaDepartment of Pharmacy, Zhongshan Hospital Fudan University, Shanghai 200032, ChinaDepartment of Pharmacy, Zhongshan Hospital Fudan University, Shanghai 200032, ChinaDepartment of Gastroenterology, Zhongshan Hospital Fudan University, Shanghai 200032, ChinaImmune checkpoint inhibitors (ICIs) significantly improve survival, while immune-mediated hepatotoxicity (IMH) has been reported. To evaluate the incidence and potential risk factors of IMH among cancer patients treated by ICIs, PubMed/Medline, Web of Science, Cochrane, and Embase were searched before 30 March 2024 for systematic review and meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated. Quality assessment was completed using the Newcastle–Ottawa scale. Of 1217 articles identified, 24 consisting of 9076 patients were included, with one study being prospective and the rest retrospective. The overall incidence of any grade IMH and grade ≥ 3 secondary to ICIs was 14% and 7%, respectively. The cholestatic pattern was more prevalent than the hepatocellular and mixed patterns. The meta-analysis revealed that ICI treatment was related to reduced risk of IMH in older patients (SMD: −0.18; 95% CI: −0.33 to −0.04), individuals with higher body mass index (WMD: −2.15; 95% CI: −3.92 to −0.38), males (OR: 0.44; 95% CI: 0.27 to 0.72), and patients with lung cancer (OR: 0.58, 95%CI 0.41 to 0.83). On the other hand, patients with liver metastasis (OR: 1.80; 95% CI: 1.47 to 2.20), history of ICI treatment (OR: 3.09; 95% CI: 1.21 to 7.89), diabetes (OR: 2.19; 95% CI: 1.36 to 3.51), chronic HBV (OR: 3.06; 95% CI: 1.11 to 8.46), and concomitant use of ICIs (OR: 8.73; 95% CI: 2.41 to 31.59) increased the risk of developing IMH. This study will provide clinicians with information on potentially high-risk groups for IMH, who need to be cautiously monitored for liver function when receiving immunotherapy.https://www.mdpi.com/1718-7729/31/11/525immunotherapyimmune-mediated hepatotoxicityincidencerisk factormeta-analysis
spellingShingle Ying Jiang
Ranyi Li
Xiaoyu Li
Ningping Zhang
Risk Factors of Immune-Mediated Hepatotoxicity Induced by Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis
Current Oncology
immunotherapy
immune-mediated hepatotoxicity
incidence
risk factor
meta-analysis
title Risk Factors of Immune-Mediated Hepatotoxicity Induced by Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis
title_full Risk Factors of Immune-Mediated Hepatotoxicity Induced by Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis
title_fullStr Risk Factors of Immune-Mediated Hepatotoxicity Induced by Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis
title_full_unstemmed Risk Factors of Immune-Mediated Hepatotoxicity Induced by Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis
title_short Risk Factors of Immune-Mediated Hepatotoxicity Induced by Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis
title_sort risk factors of immune mediated hepatotoxicity induced by immune checkpoint inhibitors in cancer patients a systematic review and meta analysis
topic immunotherapy
immune-mediated hepatotoxicity
incidence
risk factor
meta-analysis
url https://www.mdpi.com/1718-7729/31/11/525
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