Hepatocellular carcinoma (HCC) is a complex disease most commonly arising in the background of chronic liver disease. In the past two decades, there has been a significant increase in our understanding of both the clinical and molecular heterogeneity of HCC. There has been a robust increase in clinical trial activity in patients with poor prognostic factors, such as macrovascular invasion and extrahepatic spread (EHS). We aimed to synthesize the evidence for the treatment of patients with advanced HCC based on these baseline characteristics, including patients with both Child‐Pugh (CP) scores of A and B. A comprehensive search of several databases from each database inception to February 15, 2016 any language was conducted. We included 14 studies (three randomized controlled studies [RCTs] and 11 observational studies). We included studies that compared sorafenib, transarterial bland embolization/transarterial chemoembolization, yttrium‐90/radiation therapy, ablation (or combination), and no therapy. Two RCTs comparing sorafenib to best supportive care demonstrated a consistent improvement in overall survival (OS) for patients with advanced HCC and metastatic vascular invasion (MVI) and/or EHS and CP A liver disease (hazard ratio, 0.66 [95% confidence interval, 0.51‐0.87]; I2 = 0%). Several observational studies evaluated locoregional therapies alone or in combination with other treatments and were limited by very‐low‐quality of evidence. This was true for both patients with EHS and MVI. Conclusion: In patients with advanced HCC and CP A liver function, sorafenib is the only treatment that has been shown to improve OS in randomized studies. High‐quality data supporting the use of other treatment modalities in this setting, or in the setting of patients with less compensated (CP B) liver disease, are lacking. (Hepatology 2018;67:422‐435)

中文翻译：

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晚期肝细胞癌伴大血管浸润或转移性疾病的治疗：系统评价和 Meta 分析

肝细胞癌 (HCC) 是一种复杂的疾病，最常见于慢性肝病的背景下。在过去的二十年里，我们对 HCC 的临床和分子异质性的理解有了显着增加。在具有不良预后因素（例如大血管浸润和肝外扩散 (EHS)）的患者中，临床试验活动显着增加。我们旨在根据这些基线特征综合治疗晚期 HCC 患者的证据，包括 Child-Pugh (CP) 评分为 A 和 B 的患者。从每个数据库开始到 2 月 15 日对多个数据库进行全面搜索， 2016 年进行了任何语言。我们纳入了 14 项研究（三项随机对照研究 [RCT] 和 11 项观察性研究）。我们纳入了比较索拉非尼、经动脉温和栓塞/经动脉化疗栓塞、钇 90/放射治疗、消融（或联合）和无治疗的研究。两项比较索拉非尼与最佳支持治疗的随机对照试验表明，晚期 HCC 和转移性血管侵犯 (MVI) 和/或 EHS 和 CPA 肝病患者的总生存期 (OS) 持续改善（风险比，0.66 [95% 置信区间， 0.51-0.87]；I2 = 0%）。几项观察性研究单独评估了局部治疗或与其他治疗相结合，但受到极低质量证据的限制。这对于 EHS 和 MVI 患者都是如此。结论：在晚期 HCC 和 C A 肝功能患者中，索拉非尼是唯一在随机研究中显示可改善 OS 的治疗方法。缺乏支持在这种情况下或在代偿性较差 (CP B) 肝病患者的情况下使用其他治疗方式的高质量数据。（肝病学 2018 年；67：422-435）