New advances in the study of PD-1/PD-L1 inhibitors-induced liver injury

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/PDL1 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.