免疫检查点抑制剂与抗血管生成剂的联合应用已经彻底改变了晚期肝细胞癌（HCC）的治疗格局。然而，由于新研究以及达到预设主要终点的速度非常快，缺乏对一线治疗进行强有力的交叉试验比较，并且临床指南存在分歧，因此目前不存在清晰的治疗流程和疗法顺序。本文对美国和欧洲主要科学学会对晚期HCC管理的推荐进行了批判性分析，采用综合方法提供了关于这些治疗的临床益处（总生存期和无进展生存期）和安全性的信息，使用了欧洲医学肿瘤学会（ESMO）-临床益处程度评分（MCBS）和特别设计的网络荟萃分析。在指南中存在主要的一致性，即阿替伊珠单抗联合贝伐珠单抗作为一线推荐治疗的首选方案。在免疫治疗方案失败且对免疫治疗有禁忌症的患者，大多数指南都维持已建立的治疗层级结构，推荐利妥昔单抗或索拉非尼作为首选方案，其次是雷戈拉非尼、卡波替尼或拉铿玛珠单抗。迄今为止，第一线基于免疫的替妥珠单抗加杜伐雷单抗方案只在美国肝病研究学会指南和最新的全国综合癌症网络指南中被纳入，并且推荐给高危肠道出血的患者。总的来说，在一线治疗中，阿替伊珠单抗加贝伐珠单抗和硫替破单抗加IBI305（贝伐珠单抗类生物相似药）均获得了ESMO-MCBS的最高评分5分，表明具有显著的临床益处。在网络荟萃分析中，各种联合方案的总生存期无显著差异。然而，新报道的卡姆雷珠单抗加利华替尼方案与阿替伊珠单抗加贝伐珠单抗相比，治疗相关不良事件的风险显著增加（相对风险为1.59，95%置信区间为1.25-2.03，P <0.001）。本文综述发现，在一线治疗中，阿替伊珠单抗加贝伐珠单抗被认为是晚期HCC的主要标准治疗方法。从综合科学学会的指南对管理晚期HCC的建议以及交叉试验比较的新数据，这些发现可能有助于临床医生做出决策，并指导他们应对快速发展而复杂的治疗格局。

The combination of immune checkpoint inhibitors with antiangiogenic agents has revolutionized the treatment landscape of advanced hepatocellular carcinoma (HCC). However, due to rapid publication of new studies that attained their predefined primary end points, a lack of robust cross-trial comparison of first-line therapies, and diverging clinical guidelines, no clear-cut treatment flowchart and sequence of therapies are available. This critical analysis of the recommendations for the management of advanced HCC from the main scientific societies in the US and Europe adopted an integrated approach to provide information on the clinical benefit (overall survival and progression-free survival) and safety profile of these therapies using the European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) score and an ad hoc network meta-analysis.There is a major consensus among guidelines that atezolizumab plus bevacizumab has a primacy as the recommended first-line treatment of choice in advanced HCC. On progression after immunotherapy-containing regimens and for patients with contraindications for immunotherapies, most guidelines maintain the established treatment hierarchy, recommending lenvatinib or sorafenib as the preferred options, followed by either regorafenib, cabozantinib, or ramucirumab. Thus far, the first-line immune-based regimen of tremelimumab plus durvulumab has been integrated only in the American Association for the Study of Liver Diseases guidance document and the latest National Comprehensive Cancer Network guidelines and is recommended for patients with a high risk of gastrointestinal bleeding. Overall, in the first-line setting, both atezolizumab plus bevacizumab and sintilimab plus IBI305 (a bevacizumab biosimilar) received the highest ESMO-MCBS score of 5, indicating a substantial magnitude of clinical benefit. In a network meta-analysis, no significant differences in overall survival were found among the various combination regimens. However, the newly reported combination of camrelizumab plus rivoceranib was associated with a significantly higher risk of treatment-related adverse events compared with atezolizumab plus bevacizumab (relative risk, 1.59; 95% CI, 1.25-2.03; P < .001).This narrative review found that atezolizumab plus bevacizumab is regarded as the primary standard of care for advanced HCC in the first-line setting. These findings from integrating the recommendations from scientific societies' guidelines for managing advanced HCC along with new data from cross-trial comparisons may aid clinicians in decision-making and guide them through a rapidly evolving and complex treatment landscape.