Clinical characteristics and risk factors of drug-induced hepatotoxicity in cancer patients following repeated chemotherapy cycles

OBJECTIVE: This study investigates the incidence, clinical characteristics, and risk factors of drug-induced liver injury (DILI) in cancer patients undergoing multiple courses of common chemotherapy drugs, providing evidence for developing DILI prevention and control strategies in clinical practice. METHODS: A retrospective cohort study included 165 cancer patients who received multiple courses of common chemotherapy drugs between January 2023 and January 2025. Participants were divided into a study group (n = 45, DILI occurrence) and a control group (n = 120, no DILI occurrence) based on DILI development. Baseline patient data, chemotherapy regimens, and liver function indicators were collected. Univariate analysis screened potential risk factors, while multivariate logistic regression validated independent risk factors. Spearman's rank correlation analyzed associations between risk factors and DILI severity. RESULTS: The overall DILI incidence among 165 patients was 27.27% (45/165), predominantly moderate in severity. Distribution by grade was: Grade 1 (mild) 14 cases (31.11%), Grade 2 (moderate) 24 cases (53.33%), Grade 3 (severe) 7 cases (15.56%), with no Grade 4 injury. Comparison of baseline characteristics between groups revealed higher DILI incidence among patients aged ≥60 years, with alcohol consumption history, viral hepatitis history, underlying liver disease, ≥3 chemotherapy drugs, and without prophylactic hepatoprotective/cholagogue use (all p < 0.05). Post-chemotherapy, the study group exhibited significantly higher levels of ALT, AST, ALP, GGT, and TBIL compared to the control group (all p < 0.001). Multivariate analysis confirmed that age ≥60 years (OR=2.964, 95% CI: 1.247-7.043, p = 0.014), history of alcohol consumption (OR=3.684, 95% CI: 1.523-8.912, p = 0.004), history of viral hepatitis (OR=3.116, 95% CI: 1.116-8.696, p = 0.030), underlying liver disease (OR=3.293, 95% CI: 1.312-8.266, p = 0.011), use of ≥3 chemotherapy drugs (OR=1.666, 95% CI: 1.031-2.690, p = 0.037), and lack of prophylactic hepatoprotective and cholagogue medication use (OR=0.326, 95% CI: 0.137-0.772, p = 0.011) were identified as independent risk factors for DILI occurrence. Spearman analysis revealed positive correlations between age, alcohol consumption history, viral hepatitis history, underlying liver disease, and number of chemotherapy drugs with DILI severity, while a negative correlation was observed between hepatoprotective and cholagogue drug use and DILI severity. CONCLUSION: Tumor patients undergoing multiple courses of common chemotherapy drugs exhibit a high incidence of DILI, predominantly moderate in severity. Age ≥60 years, history of alcohol consumption, history of viral hepatitis, underlying liver disease, use of ≥3 chemotherapy drugs, and lack of prophylactic hepatoprotective and cholagogue drugs are independent risk factors for DILI. The first five factors are positively correlated with injury severity, while hepatoprotective and cholagogue drug use is negatively correlated. Clinicians should strengthen monitoring and implement prophylactic interventions for high-risk populations.