Effect of compound kushen injection on immune function in patients with primary liver cancer: a systematic review and meta-analysis

Yu Xiong^1,2Yutong Cai³Chenxi Li⁴Qian Yan^2,5*Xiongwen Wang^1*Xiaoying Zhang^6*

• ¹Department of Tumor, Chongqing Hospital of The First Affiliated Hospital of Guangzhou University of Chinese Medicine, chongqing, China
• ²Postdoctoral Research Station, Guangzhou University of Chinese Medicine, Guangzhou, China
• ³School of Traditional Chinese Medicine, Chongqing University of Chinese Medicine, Chongqing, China
• ⁴School of Acupuncture and Tuina, Chongqing University of Chinese Medicine, Chongqing, China
• ⁵State Key Laboratory of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine First Affiliated Hospital, Guangzhou, China
• ⁶Department of Tumor, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, China

Background: Primary liver cancer (PLC) is the third leading cause of cancer mortality worldwide. The heterogeneity of PLC and the complex immunosuppressive microenvironment make it difficult for single treatment regimens to meet patient needs. Therefore, it is crucial to find effective combination treatment strategies that enhance immune function in PLC therapy. Objective: To systematically evaluate the effect of compound kushen injection (CKI) on enhancing immune function in PLC patients and its role in treatment efficacy and related adverse reactions. Methods: Relevant Chinese and English electronic databases were searched to include randomized controlled trials (RCTs) assessing the impact of CKI on immune function in PLC patients published before June 2025. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. Statistical analyses, Sensitivity analysis and publication bias assessment were conducted using Stata 18.0 software. Results: A total of 2,359 patients from 25 RCTs were included (1,185 in the experimental group and 1,174 in the control group). Compared to conventional treatment alone, the combination of CKI This is a provisional file, not the final typeset article and conventional treatment significantly enhanced immune function, as evidenced by increased CD3⁺ levels, CD4⁺ levels, CD4+/CD8+ ratio, and natural killer (NK) cell levels, while CD8⁺ levels showed no statistical significance. Additionally, CKI improved the objective response rate (ORR) and disease control rate (DCR), reduced AFP levels, increased KPS scores and the one-year overall survival period, reduced treatment-related adverse reactions, including nausea and vomiting, hepatic dysfunction, myelosuppression, fever, and pain. Conclusion: Existing evidence suggests that the combined use of CKI and conventional treatment may positively impact immune function, therapeutic effect and treatment-related adverse reactions in patients with PLC. However, the reliability of these conclusions is limited by the absence of disease staging stratification analysis and long-term follow-up data, which are essential for confirming the long-term efficacy and safety of the combined treatment.