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血管内皮生长因子(VEGF)通路抑制剂联合免疫检查点抑制剂(ICI)在晚期肝细胞癌(HCC)的治疗中取得了较好的疗效。然而,血管内皮生长因子(VEGF)通路抑制剂联合免疫检查点抑制剂(ICI)在伴有门静脉高压(PH)的 HCC 患者中的疗效尚不清楚。

Portal hypertension is associated with poorer outcome and clinical liver decompensation in patients with HCC treated with Atezolizumab-Bevacizumab.

机构信息

AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Service d'Hépato-gastroentérologie, Paris, France.

AP-HP Sorbonne Paris Nord, Hôpitaux Universitaire Paris Seine Saint-Denis, Service d'Hépatologie, Bobigny, France; INSERM UMR 1138, Centre de recherche des Cordeliers, 75006 Paris, France.

出版信息

Dig Liver Dis. 2024 Sep;56(9):1621-1630. doi: 10.1016/j.dld.2024.02.018. Epub 2024 Mar 27.

DOI:10.1016/j.dld.2024.02.018
PMID:38548580
Abstract

BACKGROUND

Portal hypertension (PHT) often complicates hepatocellular carcinoma (HCC) treatment and prognosis. We aimed to assess PHT's impact on AtezoBev outcomes and identify predictors of acute variceal bleeding (AVB) and clinical ascites occurrence.

METHODS

A prospective cohort of 200 HCC patients treated with AtezoBev was studied alongside a retrospective cohort of 123 patients treated with Sorafenib. We assessed factors influencing progression-free survival (PFS), overall survival (OS), AVB and clinical ascites development, focusing on PHT parameters, and comparing outcomes within and between the two cohorts (time-dependent Cox model and adjusted survival curves).

RESULTS

Among the AtezoBev cohort, 10% experienced AVB, 24% had high-risk esophageal varices (EV) and 46% vascular invasion. Median PFS and OS in the AtezoBev cohort was 5.13 and 12.2 months. AVB (HR=1.81;[95%CI:1.03-3.17]) and clinical ascites occurrence (HR=2.29;[95%CI:1.52-3.45]) were independently associated with mortality. AVB incidence was 12% at 12 months in AtezoBev patients and EV, history of AVB<6months and vascular invasion were independently associated with AVB. The Sorafenib cohort had shorter median PFS and OS, with similar AVB incidence and only EV were associated with AVB.

CONCLUSIONS

PHT-related events significantly affect not only liver decompensation but also OS in AtezoBev-treated patients. We suggest a more widespread use of NSBB to prevent liver decompensation, with intensified prophylaxis for high-risk patients.

摘要

背景

门静脉高压(PHT)常使肝细胞癌(HCC)的治疗和预后复杂化。我们旨在评估 PHT 对 AtezoBev 疗效的影响,并确定急性静脉曲张出血(AVB)和临床腹水发生的预测因素。

方法

对接受 AtezoBev 治疗的 200 例 HCC 患者进行前瞻性队列研究,并对接受 Sorafenib 治疗的 123 例患者进行回顾性队列研究。我们评估了影响无进展生存期(PFS)、总生存期(OS)、AVB 和临床腹水发展的因素,重点关注 PHT 参数,并比较了两个队列内和队列间的结果(时间依赖性 Cox 模型和调整后的生存曲线)。

结果

在 AtezoBev 队列中,10%的患者发生 AVB,24%的患者存在高危食管静脉曲张(EV),46%的患者存在血管侵犯。AtezoBev 队列的中位 PFS 和 OS 分别为 5.13 和 12.2 个月。AVB(HR=1.81;95%CI:1.03-3.17)和临床腹水发生(HR=2.29;95%CI:1.52-3.45)与死亡率独立相关。AtezoBev 患者在 12 个月时的 AVB 发生率为 12%,EV、AVB<6 个月的病史和血管侵犯与 AVB 独立相关。Sorafenib 队列的中位 PFS 和 OS 更短,AVB 发生率相似,仅 EV 与 AVB 相关。

结论

PHT 相关事件不仅显著影响肝功能失代偿,而且影响 AtezoBev 治疗患者的 OS。我们建议更广泛地使用 NSBB 来预防肝功能失代偿,对高危患者加强预防。

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JHEP Rep. 2024 Dec 11;7(3):101300. doi: 10.1016/j.jhepr.2024.101300. eCollection 2025 Mar.
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Partial Splenic Embolization for Portal Hypertension Exacerbation During Atezolizumab/Bevacizumab Combination Therapy in Unresectable Hepatocellular Carcinoma.
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