A comprehensive systematic review and meta-analysis examining the risk factors for immune-mediated hepatotoxicity (IMH) in cancer patients treated with immune checkpoint inhibitors (ICIs) was recently published in Current Oncology. The study, conducted by researchers from Zhongshan Hospital Fudan University in Shanghai, China, aimed to evaluate the incidence and potential risk factors of IMH among cancer patients receiving ICI therapy.
This meta-analysis, published on November 13, 2024, included 24 studies comprising a total of 9,076 patients. The researchers conducted a thorough search of major medical databases including PubMed/Medline, Web of Science, Cochrane, and Embase for relevant articles published before March 30, 2024. The study was funded by the Clinical Key subject Construction of Shanghai.
The primary purpose of this investigation was to determine the incidence, prevalence, and risk factors of IMH following immunotherapy to provide valuable insights for clinicians managing cancer patients at potential risk. The inclusion criteria encompassed studies that included individuals diagnosed with malignancy who received treatment with ICIs, either alone or in combination, and provided information on the number of patients with any grade of IMH and those who did not develop IMH.
The meta-analysis revealed several significant findings regarding the incidence and risk factors of IMH in patients treated with ICIs. The overall incidence of any grade IMH secondary to ICIs was found to be 14%, while the incidence of grade ≥3 IMH was 7%. Interestingly, the cholestatic pattern of liver injury was more prevalent than the hepatocellular and mixed patterns.
Demographic analysis showed that ICI treatment was associated with a 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). These findings suggest that younger age, lower BMI, female gender, and non-lung cancer diagnoses may be associated with an increased risk of IMH.
Conversely, the study identified several factors that increased the risk of developing IMH. Patients with liver metastasis (OR: 1.80; 95% CI: 1.47 to 2.20), a 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 hepatitis B virus infection (OR: 3.06; 95% CI: 1.11 to 8.46), and those receiving concomitant use of multiple ICIs (OR: 8.73; 95% CI: 2.41 to 31.59) were found to have a significantly higher risk of IMH.
The study also provided insights into the clinical course of IMH, reporting that the mean time to onset of any grade IMH was 2.16 months after initiating ICI therapy, with a resolution time of approximately 1.22 months from onset. This information could be valuable for clinicians in monitoring patients and managing potential hepatotoxicity.
Despite its comprehensive nature, the study had several limitations. Most of the included studies were retrospective cohort studies, which inherently introduce potential biases. Additionally, there was a limited number of studies that provided adjusted odds ratios for specific risk variables, and the diagnostic criteria for ICI-IMH varied across studies. The authors noted that patients with severe IMH (grade III-V) were underrepresented, indicating the need for large-scale prospective investigations to further substantiate the findings.
The authors concluded that this study provides clinicians with valuable information on potentially high-risk groups for IMH, who need to be cautiously monitored for liver function when receiving immunotherapy. They emphasized the importance of recognizing these risk factors to implement appropriate monitoring strategies and early interventions.
The potential clinical impact of this meta-analysis is significant. By identifying specific risk factors for IMH in patients receiving ICI therapy, clinicians can better stratify patients and implement tailored monitoring protocols. This could lead to earlier detection and management of IMH, potentially improving patient outcomes and reducing treatment-related morbidity. Furthermore, the findings may inform future research directions, particularly in developing strategies to mitigate IMH risk in susceptible populations.
In conclusion, this meta-analysis provides a comprehensive overview of the incidence and risk factors associated with immune-mediated hepatotoxicity in cancer patients treated with immune checkpoint inhibitors. The findings underscore the importance of individualized risk assessment and close monitoring of liver function in patients receiving ICI therapy, particularly those with identified risk factors. As immunotherapy continues to play an increasingly important role in cancer treatment, understanding and managing its potential adverse effects becomes crucial for optimizing patient care and outcomes.
References
Jiang Y, Li R, Li X, Zhang N. Risk Factors of Immune-Mediated Hepatotoxicity Induced by Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis. Curr Oncol. 2024;31(11):7129-7143. Published 2024 Nov 13. doi:10.3390/curroncol31110525
