目的：系统评估经动脉化疗栓塞（TACE）和酪氨酸激酶抑制剂（TKI）联合（TT）联合或不联合PD-1 抗体（PD-1Ab）治 疗晚期肝细胞癌（aHCC）的疗效与潜在不良反应（AE）。方法：检索PubMed、中国知网（CNKI）、Embase、Web of Science等数据 库，时限为各数据库建库始至 2024 年 1 月 31 日。由 2 位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后，采用 Stata16.0软件进行Meta分析。结果：纳入17项研究，共2 334例aHCC患者。Meta分析结果显示，与TT疗法相比，PD-1Ab的加 入能显著改善aHCC患者的总生存期（OS）[HR = 0.44，95% C（I 0.36，0.51），P < 0.000 01]和无进展生存期（PFS）[HR = 0.47，95% C（I 0.42，0.52），P < 0.000 01]，同时提高aHCC患者的客观缓解率（ORR）[HR = 1.65，95% C（I 1.46，1.86），P < 0.000 01]和疾病控制 率（DCR）[HR = 1.26，95% C（I 1.15，1.38），P < 0.000 01]；不同基线资料如ECOG-PS、肝外转移与否、BCLC分期、肿瘤大小、ChildPugh评分及肝门静脉侵犯与否等aHCC患者均可从TT PD-1Ab疗法中获益；两治疗方案间全级别与 ≥3级AE的总发生率无显著 差异，但高血压、甲状腺功能减退及反应性皮肤血管增生等症状在接受TT PD-1Ab治疗的患者中更为常见。结论：相较于TT疗 法，PD-1Ab的加入可显著延长aHCC患者OS和PFS，并提高其整体ORR与DCR；TT PD-1Ab治疗组患者发生全级别及≥ 3级AE 的整体发生率没有显著增加，整体耐受性良好，但在高血压、皮肤与黏膜及甲状腺AE上有较高的发生率，应予以重视。

Objective: To evaluate the efficacy and potential adverse effects of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) [TT] with or without PD-1 antibody (PD-1Ab) (TT + PD-1Ab vs TT alone) in the treatment of advanced hepatocellular carcinoma (aHCC). Methods: A literature search was conducted across PubMed, CNKI, Embase, and Web of Science from database inception to January 31, 2024. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Meta-analysis was performed using Stata16.0 software. Results: A total of 17 studies involving 2 334 patients were included. The meta-analysis results showed that: Compared with TT therapy, the addition of PD-1 antibody significantly improved overall survival [HR = 0.44, 95% CI (0.36, 0.51), P < 0.000 01 ], progression-free survival[HR = 0.47, 95% CI (0.42, 0.52), P < 0.000 01], objective response rate (ORR) [HR = 1.65, 95% CI (1.46, 1.86), P < 0.000 01], and disease control rate (DCR) (HR = 1.26, 95% CI [1.15, 1.38], P < 0.000 01); aHCC patients with different baseline characteristics such as ECOG-PS, extrahepatic metastasis, BCLC stage, tumor size, Child-Pugh score, and hepatic portal vein invasion benefited from TT + PD-1Ab therapy; There was no significant difference in the overall incidence of all-grades and ≥ grade 3 adverse events (AEs) between the two regimens, but symptoms such as hypertension, hypothyroidism, and reactive cutaneous vascular proliferation were more common in patients treated with TT + PD-1Ab. Conclusion: Compared with the TT therapy, the addition of PD-1Ab can significantly extend OS and PFS and improve the ORR and DCR in patients with aHCC. The overall incidence of all-grades and ≥ grade 3 AEs was not significantly increased in the TT PD-1 Ab group, with good overall tolerability, although higher rates of hypertension, mucocutaneous, and thyroidrelated AEs were observed in the TT + PD-1Ab group and should be closely monitored.

福建省自然科学基金（No. 2023J011485）；福州市科技计划项目（No. 2023S-026）；福州市卫生健康科技计划（No. 2022-S-wq9）