Objective: To study the clinical features and prognostic impact of transarterial chemoembolization (TACE), immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs) combination therapy regimens in the treatment of patients with hepatitis B virus-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis. Methods: Patients with HBV-related intermediate-and advanced-stage hepatocellular carcinoma (HBV) who visited the Affiliated Hospital of Xuzhou Medical University between January 1, 2020, and December 31, 2022, were enrolled. TACE+TKIs +ICIs combination therapy was used to treat all patients. The occurrence and factors influencing cholestasis, as well as the impact on prognosis after combined therapy, were analyzed. The measurement data were compared using a t-test and a non-parametric rank sum test. The count data was compared using the χ(2) test. The survival rates were compared using a log-rank test between different groups. Results: A total of 106 cases with HBV-related intermediate-and advanced-stage hepatocellular carcinoma were enrolled. The probabilities of secondary cholestasis within 3 and 6 months, 1, 2, and 3 years after TACE+ICIs+TKIs combination therapy were 9.4%, 12.3%, 14.2%, 24.5%, and 24.5%, respectively. Patients with secondary cholestasis had persistent symptoms and rapid progression. During the treatment course, the median survival time was significantly longer in patients with hepatocellular carcinoma without secondary cholestasis than that of patients with cholestasis (26.9 months vs. 13.7 months, respectively, P < 0.05). Secondary cholestasis, baseline aspartate aminotransferase, and prothrombin activity levels were independent risk factors that affected the survival and prognosis of patients treated with combination therapy. There was no statistically significant difference in the occurrence of other adverse reactions between the two groups with secondary and non-secondary cholestasis during the treatment course (47.5% vs. 43.3%, χ(2)=0.058, P = 0.810). Conclusion: TACE+ICIs+TKIs therapy combination is relatively common in the treatment of patients with HBV-related intermediate-and advanced-stage hepatocellular carcinoma with secondary cholestasis. Moreover, accelerated disease progression is an independent risk factor affecting the survival and prognosis of patients.
目的： 探讨经动脉插管化疗栓塞术（TACE）、免疫检查点抑制剂（ICIs）及酪氨酸激酶抑制剂（TKIs）联合方案治疗乙型肝炎病毒（HBV）相关中晚期肝细胞癌患者继发胆汁淤积的临床特点及其对患者预后的影响。 方法： 纳入2020年1月1日至2022年12月31日于徐州医科大学附属医院就诊的HBV相关中晚期肝细胞癌患者，所有患者均采用TACE+TKIs+ICIs联合治疗，分析患者经联合治疗后胆汁淤积的发生情况及其影响因素，进一步分析其对预后的影响。计量资料数据比较采用t检验、非参数秩和检验；计数资料比较采用χ(2)检验；不同组别生存率比较采用Log-rank法检验。 结果： 共纳入106例HBV相关中晚期肝细胞癌患者，经TACE+ICIs+TKIs联合治疗后3、6个月及1年、2年、3年内继发胆汁淤积的概率分别为9.4%、12.3%、14.2%、24.5%、24.5%。继发胆汁淤积的患者症状多数持续存在，并快速进展。治疗过程中未继发胆汁淤积肝细胞癌患者的中位生存时间明显长于发生胆汁淤积患者（26.9个月与13.7个月，P < 0.05）。继发胆汁淤积、基线天冬氨酸转氨酶、凝血酶原活动度是影响联合治疗患者生存预后的独立危险因素。治疗过程中继发与未继发胆汁淤积两组患者的其他不良反应发生率差异无统计学意义（47.5%与43.3%，χ(2)=0.058，P =0.810）。 结论： TACE+ICIs+TKIs联合治疗HBV相关中晚期肝细胞癌患者继发胆汁淤积较为常见，并且病情进展较快，是影响患者生存预后的独立危险因素。.
Keywords: Cholestasis; Hepatocellular carcinoma; Immune checkpoint inhibitors; Transcatheter arterial chemoembolization; Tyrosine kinase inhibitor.