Liver Injury Affects One in Eight Patients on Immune Checkpoint Inhibitors in Real-World Study

Patients treated with immune checkpoint inhibitors (ICIs) developed liver injury at a rate of 12.17 percent in a retrospective study of 682 people treated at Tianjin Union Medical Center between January 2020 and June 2024, according to a real-world analysis published in Frontiers in Pharmacology. Of the 83 patients who experienced ICI-related liver injury, the overwhelming majority — 73.49 percent — showed a cholestatic pattern, in which bile flow is disrupted, while 20.48 percent had mixed injury and only 6.02 percent had a purely hepatocellular pattern dominated by liver cell damage. The Tianjin team set out to map how this immune-related liver injury presents, how severe it becomes, and which patients recover their liver function within six months of the event.

The severity of liver injury tracked closely with routine blood tests. Patients with more severe injury had higher baseline levels of alkaline phosphatase (ALP), gamma-glutamyl transferase and total bilirubin, and reached higher peak values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the enzymes that leak into the bloodstream when liver cells are damaged. The dynamics of injury also differed sharply by subtype. Hepatocellular injury produced rapid surges in ALT and AST, whereas cholestatic injury caused a marked but noticeably slower rise in ALP, and mixed injury combined features of both patterns. Cholestatic injury emerged as the dominant subtype in patients receiving PD-1/PD-L1 inhibitor-containing regimens, and the pattern of change in liver function tests varied systematically with the clinical subtype.

To identify who fails to recover within six months, the team examined a range of clinical variables. In univariate analysis, older age, higher peak ALT and a neutrophil-to-lymphocyte ratio (NLR) above 3 were each associated with poor recovery. When the variables were tested together in a multivariate model, only NLR above 3 remained independently associated with failure to recover liver function within six months, with an odds ratio of 10.917 (95 percent confidence interval 1.552 to 76.817, P = 0.016).

Receiver operating characteristic analysis supported the signal: the continuous NLR yielded an area under the curve of 0.702 with a cut-off of 2.955, rounded to 3, while the binary NLR greater than 3 yielded an AUC of 0.694. These are moderate discriminatory values, and the authors frame NLR as an exploratory candidate biomarker that warrants further investigation rather than a validated clinical tool.

The study’s design shapes how its findings should be read. It was a single-center retrospective cohort, so the patient mix, treatment protocols and monitoring practices at one hospital in Tianjin may not generalize everywhere. Follow-up was censored in December 2024 with a minimum of six months, which allowed recovery assessment but not longer-term outcomes. As an observational analysis, it identifies associations, not causal effects, and the wide confidence interval around the NLR odds ratio reflects the modest number of patients who failed to recover. Within those limits, the work documents that cholestatic injury predominated under PD-1/PD-L1 inhibitor-containing therapy, that liver function parameters changed in distinct patterns according to subtype, and that NLR above 3 merits further study as a potential exploratory marker of poor six-month recovery in ICI-related liver injury.

Subject of Research: Liver injury in patients receiving immune checkpoint inhibitor-based therapy

Article Title: Clinical characteristics and prognosis of liver injury in patients receiving immune checkpoint inhibitor-based therapy: a real-world retrospective study

Article References: Gao, L., Yang, X., Yang, F., Shi, G., Jiang, Y., Zhao, Z., Wang, M., Gao, Y., & Han, T. (2026). Clinical characteristics and prognosis of liver injury in patients receiving immune checkpoint inhibitor-based therapy: a real-world retrospective study. Frontiers in Pharmacology, 17, Article 1957181. https://doi.org/10.3389/fphar.2026.1957181

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1957181

Keywords: immune checkpoint inhibitors, liver injury, cholestatic injury, hepatotoxicity, PD-1, neutrophil-to-lymphocyte ratio, retrospective study, liver function tests, immunotherapy, prognosis, Clinical, characteristics