New advances in the study of PD-1/PD-L1 inhibitors-induced liver injury
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Updated: Jul 18, 2026
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Meijun Yue1, Chunyu Li1, Guohui Li1
1National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Abstract:
The application of immune checkpoint inhibitors (ICIs) has made extraordinary achievements in tumor treatment. Among them, programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors can improve the prognosis of advanced tumors, and have been widely used in clinical practice to treat many types of cancers. However, excessive immune response can also induce immune-related adverse events (irAEs) involving many organs. Of these, immune-related liver injury is the relatively common and carries the highest morbidity, which has attracted the attention of hepatologists all over the world. The incidence of this type of liver injury depends specifically on factors such as the type of drug being combined, viral infection, type of cancer and liver transplantation. Although there is no unanimity on the mechanism of PD-1/PD-L1 inhibitor-induced liver injury, in this review, we also summarize the current evidence that provides insights into the pathogenesis of PD-1/PD-L1 inhibitor-induced liver injury, including the fact that PD-1/PD-L1 inhibitors cause reactivation of CTLs, aberrant presentation of autoantigens, hepatic immune tolerance environment is disrupted, and cytokine secretion, among other effects. Patients usually develop liver injury after the use of PD-1/PD-L1 inhibitors, and clinical symptoms mainly include weakness, muscle pain, nausea and vomiting, and jaundice. Histologically, the main manifestation is lobular hepatitis with lobular inflammatory infiltration. Since the specific biomarkers for PD-1/PD-L1 inhibitor-associated liver injury have not been identified yet, alpha-fetoprotein, IL-6, and IL-33 have the potential to be biomarkers for predicting this type of liver injury in the future, but this requires further research. We also describe the examination and treatment of this type of liver injury, which usually includes eliminating related influencing factors, regularly monitoring liver function, temporarily retaining or permanently stopping ICIs treatment according to the severity of toxicity, and using corticosteroids. This review may provide useful information for the future clinical practice of PD-1/PD-L1 inhibitors.
Insights
Immune checkpoint inhibitors (ICIs) like PD-1/PD-L1 blockers treat cancer but can cause liver injury. This review explores their mechanisms, symptoms, and management strategies for this common side effect.
Area of Science:
- Oncology
- Immunology
- Hepatology
Background:
- Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 inhibitors, are effective in treating advanced cancers.
- However, ICIs can lead to immune-related adverse events (irAEs), with liver injury being a common and significant concern.
Purpose of the Study:
- To review the pathogenesis, clinical manifestations, and histological features of PD-1/PD-L1 inhibitor-induced liver injury.
- To summarize current understanding and potential future directions for diagnosis and management.
Main Methods:
- Review of existing literature on PD-1/PD-L1 inhibitor-induced liver injury.
- Summary of proposed mechanisms, including immune cell reactivation and disruption of hepatic immune tolerance.
- Description of clinical presentation, histological findings, and diagnostic approaches.
Main Results:
- PD-1/PD-L1 inhibitors can cause liver injury through mechanisms like T-cell reactivation and altered immune tolerance.
- Clinical symptoms include fatigue, nausea, and jaundice, with lobular hepatitis observed histologically.
- No specific biomarkers exist, but alpha-fetoprotein, IL-6, and IL-33 show potential.
Conclusions:
- PD-1/PD-L1 inhibitor-induced liver injury is a critical irAE requiring careful monitoring and management.
- Early detection and intervention, including corticosteroid use and adjusting ICI therapy, are crucial.
- Further research is needed to identify reliable biomarkers for prediction and diagnosis.
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