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Volume 42 Issue 4
Apr.  2026
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Article Navigation >  Journal of Clinical Hepatology  > 2026  >  42(4): 874-881

Efficacy of Zishen Huoxue Formula in treatment of molecular-targeted therapy-associated proteinuria in patients with primary liver cancer

DOI: 10.12449/JCH260416
  • 1.

    Department of Traditional Chinese Medicine and Hepatology，Chinese PLA General Hospital，Beijing 100039，China

  • 2.

    Department of Hepatology，Senior Department of Hepatology，Chinese PLA General Hospital，Beijing 100039，China

  • 3.

    China Military Institute of Chinese Medicine，Department of Hepatology，Chinese PLA General Hospital，Beijing 100039，China

Research funding:

National Science and Technology Major Project for Research on Prevention and Treatment of Cancer, Cardiovascular and Cerebrovascular Diseases, Respiratory Diseases, and Metabolic Diseases (2024ZD0526203);

National Natural Science Foundation of China (82104702)

  • Received Date: 2025-09-15
  • Accepted Date: 2025-12-09
  • Published Date: 2026-04-25
    Abstract
  •   Objective  To investigate the effect of Zishen Huoxue Formula （ZSXHF） on molecular-targeted therapy-associated proteinuria in patients with primary liver cancer （PLC）， to assess the efficacy of ZSXHF in the treatment of molecular-targeted therapy-associated proteinuria， and to provide a basis for clinical medication.  Methods  A retrospective cohort study was conducted among the PLC patients with molecular-targeted therapy-associated proteinuria who were diagnosed and treated in The Department of Hepatology of Chinese PLA General Hospital， from January 1， 2022 to July 1， 2025. With ZSXHF treatment as the exposure factor， the patients with a cumulative treatment duration of ≥9 weeks were enrolled as traditional Chinese medicine （TCM） group， while those without TCM treatment were enrolled as control group. Propensity score matching was performed for the two groups at a ratio of 1∶1 based on sex， age， 24-hour urinary protein， blood urea nitrogen， and serum creatinine. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. Univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for promoting the improvement of targeted-therapy-associated proteinuria.  Results  A total of 137 PLC patients with targeted-therapy-associated proteinuria were enrolled， with 34 patients in the TCM group and 103 in the control group. After follow-up for 6 months， the TCM group had a significant improvement in urinary protein grade compared with the control group （χ2=9.261， P=0.016）. There were 25 patients in each group after propensity score matching， and after follow-up for 6 months， there were significant differences between the two groups in urinary protein grade （χ2=15.689， P<0.001） and 24-hour urinary protein （Z=-3.075， P=0.002）. After cumulative treatment with ZSXHF for ≥9 weeks， the TCM group had a significantly greater change in 24-hour urinary protein from baseline compared with the control group （t=-2.514， P=0.016）， while there were no significant differences in the changes in liver and renal function after ZSXHF intervention between the two groups （all P>0.05）. The multivariate Logistic regression analysis showed that ZSXHF treatment （odds ratio=2.901， 95% confidence interval： 1.135 — 7.417， P=0.026） was an independent influencing factor for improvement in molecular-targeted therapy-associated proteinuria.  Conclusion  ZSHXF can effectively alleviate molecular-targeted therapy-associated proteinuria in PLC patients with a favorable safety profile， which provides a new reference for TCM prevention and treatment of molecular-targeted therapy-associated adverse reactions in PLC patients.

     

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