肝细胞癌（HCC）是全球第三大致命恶性肿瘤。近年来，随着免疫检查点抑制剂在晚期HCC患者中的免疫治疗的快速发展，许多随机临床试验（RCTs）证明这些患者的生存益处。本系统评价和荟萃分析旨在确定先进HCC患者的特定临床病理特征，可能导致对免疫治疗在整体生存期（OS）、无进展生存期（PFS）和客观缓解率（ORR）方面偏好反应。所包括的临床试验从2002年1月1日至2022年10月20日间英文发表的PubMed、Embase、Cochrane图书馆和Web of Science数据库中检索，对第一和第二线Ⅱ/Ⅲ期研究的免疫治疗患有先进HCC的系统评价和荟萃分析，使用OS作为主要的结果评估指标，PFS和ORR作为次要的结果评估指标，以获取可能偏好对PD-1和PD-L1抑制剂的患者的临床病理特征。毒性和特定与治疗相关的不良事件（TRAEs）也被确定。在筛选了1392项相关研究后，本系统评价和荟萃分析纳入了12项研究，总共包括5948名患者。基于相互作用分析，第一线免疫治疗后的OS在病毒性肝炎亚组（HR=0.73 vs 0.87，相互作用p值=0.02）和微血管侵犯（MVI）和/或肝外蔓延（EHS）亚组（HR=0.73 vs 0.89，相互作用p值=0.02）之间的差异是显著的。病毒性肝炎亚组的PFS差异非常显著（汇总HR=0.55 vs 0.81，相互作用p值=0.007）。在第二线免疫治疗后，预测巴塞罗那临床肝癌（BCLC）分期亚组之间ORR的差异是显著的（汇总ES=0.12 vs 0.23，相互作用p值=0.04）。与PD-L1抑制剂相比，PD-1抑制剂可能更有可能引起TRAEs。腹泻、天门冬氨酸氨基转移酶升高和高血压是前三位的TRAEs。本系统评价和荟萃分析代表了首个试点研究，旨在确定肝细胞癌患者的关键临床病理特征，可能预测免疫治疗的有利治疗结果，包括OS、PFS和ORR。研究结果表明，病毒性肝炎（尤其是乙型肝炎病毒）和MVI和/或EHS的阳性患者在接受PD-1/PD-L1免疫检查点抑制剂治疗时，可能有更多的OS受益。

Hepatocellular carcinoma (HCC) is the third most lethal malignant tumor worldwide. The rapid development of immunotherapy utilizing immune checkpoint inhibitors for advanced HCC patients has been witnessed in recent years, along with numerous randomized clinical trials (RCTs) demonstrating the survival benefits for these individuals. This systematic review and meta-analysis aimed to identify specific clinico-pathological characteristics of advanced HCC patients that may lead to preferable responses to immunotherapy in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).The included clinical trials were retrieved from PubMed, Embase, Cochrane library, and Web of Science databases published in English between January 1, 2002, and October 20, 2022. A systematic review and meta-analysis for first and second-line phase II/III studies were conducted on immunotherapy for patients with advanced HCC by using OS as the primary outcome measure, and PFS and ORR as the secondary outcome measures to obtain clinico-pathological characteristics of patients which might be preferable responses to PD-1 and PD-L1 inhibitors. Toxicity and specific treatment-related adverse events (TRAEs) were also determined.After screening 1392 relevant studies, 12 studies were included in this systematic review and meta-analysis to include 5948 patients. Based on the analysis of interaction, the difference in OS after first-line immunotherapy between the subgroups of viral hepatitis (HR=0.73 vs 0.87, p for interaction=0.02) and microvascular invasion (MVI) and/or extrahepatic spread (EHS) (HR=0.73 vs 0.89, p for interaction=0.02) were significant. The difference in PFS between the subgroups of viral hepatitis was highly significant (pooled HR=0.55 vs 0.81, p for interaction=0.007). After second-line immunotherapy, the difference in ORR between the subgroups of Barcelona Clinic Liver Cancer was significant (pooled ES=0.12 vs 0.23, p for interaction=0.04). Compared with programmed cell death-Ligand 1 (PD-L1) inhibitors, programmed death-1 (PD-1) inhibitors may have a higher probability to cause TRAEs. Diarrhea, increased aspartate aminotransferase and hypertension were the top 3 TRAEs.This systematic review and meta-analysis represents the first pilot study aimed at identifying crucial clinico-pathological characteristics of patients with advanced HCC that may predict favorable treatment outcomes in terms of OS、PFS and ORR to immunotherapy. Findings suggest that patients with viral hepatitis positivity (especially hepatitis B virus) and MVI and/or EHS may benefit more in OS when treated with PD-1/PD-L1 immune checkpoint inhibitors.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.