晚期肝细胞癌（HCC）已采用靶向治疗、免疫治疗或两者联合治疗，但总体临床疗效仍不理想。肝动脉灌注化疗（HAIC）作为一种局部治疗方式，对伴有门静脉癌栓和广泛肝内转移的晚期肝癌患者显示出良好的治疗效果。近年来，HAIC与免疫、靶向治疗相结合逐渐得到东亚国家的认可。然而，还需要进一步研究来评估这种三联疗法的有效性和安全性。系统检索了 PubMed、Embase、Cochrane Library 和 Web of Science 数据库中过去 5 年内进行的 HAIC 联合免疫治疗和靶向治疗的研究：晚期 HCC 的一线治疗。根据系统评价和荟萃分析的首选报告项目（PRISMA）指南，我们进行了这项荟萃分析。此外，纳入研究的质量还使用乔安娜·布里格斯研究所 (JBI) 量表进行评估。从符合条件的研究中提取并汇总了总体缓解率 (ORR)、疾病控制率 (DCR)、无进展生存期 (PFS)、总体生存期 (OS) 和不良事件 (AE) 等结果。 12 项研究涉及 1072 名患者参加了这项荟萃分析。就肿瘤反应而言，合并的 ORR 和 DCR 分别为 65.7%（95% CI，58.7%-72.7%）（I2 = 83%，P = 0.000）和 89.2%（95% CI，83.9%-93.6%）（ I2 = 83%，P = 0.000）。在分析 PFS 时，一项研究中未达到 PFS 95% 置信区间的上限，这可能会影响统计分析。因此，我们分析了其余 11 项研究共 1019 名患者的 mPFS，最终汇总 mPFS 为 9.77 个月（95% CI，7.73-11.80）（I2 = 93.9%，P = 0.000）。一些研究的随访时间不足，只有 8 项研究报告了 OS，我们系统分析了这 8 项研究并提取出汇总的 mOS 为 16.65 个月（95% CI，14.17-19.14）（I2 = 76.9%，P = 0.000）。安全性方面，各级别AE发生率从高到低依次为：转氨酶升高（61.3%）、恶心呕吐（40.5%）、高血压（37.8%）、血小板减少（37.4%）、高胆红素血症（36.7%）、腹痛（35.6%）、白细胞减少（34.6%）、甲状腺功能减退（19.0%）、皮疹（14.4%）。 3-4级AE从高到低依次为：转氨酶升高（10.8%）、血小板减少（7.9%）、高血压（7.4%）、白细胞减少（5.0%）。无治疗相关死亡发生，接受该三联疗法的患者表现出良好的耐受性。肝动脉灌注化疗联合酪氨酸激酶抑制剂和免疫检查点抑制剂作为不可切除的晚期HCC的一线治疗显示出良好的疗效和良好的安全性。版权© 2024。由爱思唯尔公司出版。

Advanced hepatocellular carcinoma (HCC) has been treated with targeted therapy, immunotherapy, or a combination of both, however, the overall clinical efficacy is still unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC), as a localized treatment modality, has demonstrated favorable therapeutic efficacy in patients with advanced HCC accompanied by portal vein tumor thrombus and extensive intrahepatic metastasis. In recent years, the combination of HAIC with immune and targeted therapy has gradually gained acceptance in East Asian countries. However, further investigation is necessary to assess the efficacy and safety of this triple therapy.PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for studies conducted within the past 5 years on HAIC combined with immunotherapy and targeted therapy as first-line treatment for advanced HCC. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted this meta-analysis. Additionally, the quality of included studies was assessed using the Joanna Briggs Institute (JBI) scale. Outcomes such as overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs)were extracted and pooled from eligible studies.Twelve studies involving 1072 patients were enrolled in this meta-analysis. In terms of tumor response, the pooled ORR and DCR were 65.7% (95% CI, 58.7%-72.7%) (I2 = 83%, P = 0.000) and 89.2% (95% CI, 83.9%-93.6%) (I2 = 83%, P = 0.000), respectively. When analyzing PFS, the upper limit of 95% confidence interval of PFS in one study was not reached, which could potentially impact the statistical analysis. Therefore, we analyzed the remaining 11 studies a total of 1019 patients to pool mPFS, ultimately the pooled mPFS was 9.77months (95% CI, 7.73-11.80) (I2 = 93.9%, P = 0.000). Follow-up time in some studies was insufficient, only eight studies reported OS, we systematically analyzed these eight studies and extracted the pooled mOS was 16.65 months (95% CI, 14.17-19.14) (I2 = 76.9%, P = 0.000). In terms of safety, the incidence rates of any grade AEs, ranked from high to low, were as follows: aminotransferase increased (61.3%), nausea and vomiting (40.5%), hypertension (37.8%), thrombocytopenia (37.4%), hyperbilirubinemia (36.7%), abdominal pain (35.6%), leukopenia (34.6%), hypothyroidism (19.0%), rash (14.4%). Grade 3-4 AEs ranked from high to low were as follows: aminotransferase increased (10.8%), thrombocytopenia (7.9%), hypertension (7.4%), leukopenia (5.0%). No treatment-related deaths occurred, patients receiving this triple therapy demonstrated favorable tolerability.The combination of hepatic arterial infusion chemotherapy with tyrosine kinase inhibitors and immune checkpoint inhibitors as a first-line therapy for unresectable advanced HCC demonstrates promising therapeutic efficacy and favorable safety.Copyright © 2024. Published by Elsevier Inc.