[Study on the comparison of postoperative liver injury caused by hepatic arterial perfusion chemotherapy combined with targeted immunotherapy with hepatic arterial chemoembolization combined with targeted immunotherapy for intermediate-and advanced-stage liver cancer].

Objective: To compare the postoperative liver function injury condition in patients with intermediate-and advanced-stage hepatocellular carcinoma (HCC) treated with hepatic artery infusion chemotherapy (HAIC) and hepatic artery chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and multi-target tyrosine kinase inhibitors (TKIs). Methods: Patients with intermediate-and advanced-stage HCC who were admitted and treated with HAIC/TACE+ICIs+TKIs therapy at Nanfang Hospital of Southern Medical University from January 2019 to November 2021, with follow-up up to July 2023, were retrospectively enrolled. The results of liver function tests within one week before interventional surgery and on the first day after surgery were recorded. The degree of postoperative liver injury was graded according to the common terminology criteria for adverse events 5.0 (CTCAE 5.0). The treatment efficacy was evaluated according to RECIST 1.1 criteria. Measurement data were compared between groups using a t-test or a non-parametric rank sum test. Enumeration data were compared between the groups using the χ(2) test or Fisher's exact probability method. The survival condition differences were analyzed by the log-rank method. Results: This study included 82 and 77 cases in the HAIC and TACE groups. There were no statistically significant differences between the two groups of patients in terms of gender, age, physical condition score, number of tumors, presence or absence of liver cirrhosis, Child-Pugh grade, albumin-bilirubin (ALBI) grade, and combined ICIs and TKIs . The HAIC group had later tumor staging, a greater tumor burden, poorer liver reserve function, and a larger proportion of patients in stage C (81.7% vs. 63.6%), χ(2)=6.573, P = 0.01). There were 53 cases (64.6% vs. 32.5%) with a maximum tumor diameter of ≥ 10cm, χ(2)=16.441, P < 0.001), and more patients had a retention rate of ≥ 10% for indocyanine green (ICG) at 15 minutes (68.3% vs. 51.9%, P = 0.035). The postoperative incidence rate of increased levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin was significantly lower in the HAIC group than that in the TACE group (28.0% vs. 63.6%, χ(2)=20.298, P < 0.001, 54.9% vs. 85.7%, χ(2)=17.917, P < 0.001;40.2% vs. 55.8%, χ(2)=3.873, P = 0.049). The number of patients with postoperative ALBI grade 3 was significantly lower in the HAIC group than that in the TACE group (6.1% vs. 16.9%, χ(2)=4.601, P = 0.032). There was no statistically significant difference in the incidence rate of postoperative hypoalbuminemia, activated partial thromboplastin time, or increased international standardized ratio between the two groups of patients. There was no statistically significant difference in median progression-free survival (7.3 months vs. 8.2 months, P = 0.296) or median overall survival (16.5 months vs. 21.9 months, P = 0.678) between the two groups of patients. Conclusion: The incidence rate of postoperative liver injury is higher in patients with intermediate-and advanced-stage HCC treated with TACE combined with ICIs and TKIs than in patients with HAIC combined with ICIs and TKIs.目的： 对比分析肝动脉灌注化疗术（HAIC）和经动脉插管化疗栓塞术（TACE）联合免疫检查点抑制剂（ICIs）和多靶点酪氨酸激酶抑制剂（TKIs）治疗中晚期肝细胞癌（HCC）患者术后肝功能损伤的情况。 方法： 回顾性纳入2019年1月至2021年11月收治于南方医科大学南方医院行HAIC/TACE+ICIs+TKIs治疗的中晚期HCC患者，随访截至2023年7月。记录介入术前1周内及术后第1天肝功能检查结果，根据常见不良反应事件评价标准(CTCAE) 5.0对术后肝损伤程度进行分级，参照实体肿瘤的反应评价1.1标准进行疗效评估。计量资料组间数据比较采用t检验或非参数秩和检验；计数资料组间数据比较采用χ(2)检验或Fisher精确概率法；采用Log-rank法分析生存情况的差异。 结果： 研究纳入HAIC组82例患者，TACE组77例。两组患者的性别、年龄、体力状态评分、肿瘤数量、有无肝硬化、Child-Pugh分级、白蛋白-胆红素（ALBI）分级及联合的ICIs和TKIs方案差异无统计学意义。HAIC组患者肿瘤分期更晚，肿瘤负荷更重，肝储备功能更差，BCLC分期C期患者比例更高（81.7%与63.6%，χ(2)=6.712，P = 0.01），肿瘤最大直径≥10 cm的患者有53例（64.6%与32.5%，χ(2)=16.441，P < 0.001），吲哚菁绿（ICG）15 min滞留率≥10%的患者更多（68.3%与51.9%，P = 0.035）。HAIC组术后丙氨酸转氨酶、天冬氨酸转氨酶、总胆红素水平升高的发生率均显著低于TACE组，分别为28.0%与63.6%，χ(2)=20.298，P < 0.001；54.9%与85.7%，χ(2)=17.917，P < 0.001；40.2%与55.8%，χ(2)=3.873，P = 0.049。HAIC组术后ALBI分级为3级的患者显著少于TACE组（6.1%与16.9%，χ(2)=4.601，P = 0.032）。两组患者术后低白蛋白血症、活化部分凝血活酶时间和国际标准化比值升高的发生率差异无统计学意义。两组患者中位无进展生存期（7.3个月与8.2个月，P = 0.296）及中位总生存期（16.5个月与21.9个月，P = 0.678）差异无统计学意义。 结论： TACE联合ICIs和TKIs治疗中晚期HCC患者术后肝损伤发生率高于HAIC联合ICIs和TKIs治疗。.