肝硬化患者胃静脉曲张出血的预防性TIPS (GAVAPROSEC)：一项开放标签随机临床试验

IF 38.6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Lancet Gastroenterology & Hepatology Pub Date : 2025-06-12 DOI:10.1016/s2468-1253(25)00156-6

Jean-Paul Cervoni, Delphine Weil, Maxime Desmarets, Adrien Lannes, Louis D'Alteroche, Charlotte Bouzbib, Hélène Larrue, Elise Lemaitre, Stéphanie Faure, Mariane Latournerie, Caroline Jézéquel, Claire Billioud, Nicolas Carbonell, Faouzi Saliba, Florence Tanné, Jean-Baptiste Hiriart, Isabelle Olivier-Hourmand, Eric Nguyen Khac, Isabelle Archambeaud, Marie-Noelle Hilleret, Teresa Antonini

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引用次数: 0

摘要

背景：在肝硬化患者中，静脉曲张胶闭塞术被推荐用于治疗急性底静脉曲张出血，并与非选择性β受体阻滞剂（NSBB）联合用于预防再出血。我们评估了先发制人的经颈静脉肝内门静脉系统分流术（p-TIPS）在这种情况下的疗效。方法该开放标签随机试验在法国的17个三级中心进行。肝硬化和急性底静脉曲张出血（不包括1型胃食管静脉曲张）的患者，通过内镜注射胶和血管活性治疗实现初始止血，并保持稳定至少12小时，随机分配在72小时内接受有盖p-TIPS或继续按需胶闭塞联合NSBB。随机化集中，按中心分层，并以4个块（1:1比例）进行。主要的综合终点是1年内的全因死亡率或有临床意义的再出血。对改良意向治疗（mITT）人群进行分析。该研究已在ClinicalTrials.gov注册（NCT03705078）。在2019年1月3日至2023年2月25日期间，对292名患者进行了筛查，其中105名患者入组并随机分配。在排除2例随机错误分配的患者和2例撤回同意的患者后，101例患者被纳入mITT人群（平均年龄58.2岁[SD 9.7]， 81例[80%]男性，91例[90%]酒精相关性肝硬化，平均MELD评分14.3 [SD 5.0]）。在101例患者中，47例分配到p-TIPS， 54例分配到胶闭塞和NSBB。p-TIPS组1年内无死亡或再出血的概率为77% (95% CI 62-87)，而胶闭塞和NSBB组为37%(24-50)(风险比0.25 [95% CI 0.12 - 0.51]；术;0·0001)。对照组20例（37%）患者需要行TIPS抢救。8例患者出现胶迁移（p-TIPS组3例[6%]，对照组5例[9%]）。p-TIPS组出现1例心脏失代偿。肝性脑病的1年累积发病率在两组之间相似（35% [95% CI 21-49] vs 32%[19-45]）。对于肝硬化和急性底静脉曲张出血的患者，p-TIPS可显著降低1年再出血或死亡的风险，应考虑作为一线治疗。资助法国卫生部。

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Pre-emptive TIPS for gastric variceal bleeding in patients with cirrhosis (GAVAPROSEC): an open-label randomised clinical trial

Background

In patients with cirrhosis, variceal glue obliteration is recommended for the treatment of acute fundal variceal bleeding, and for the prevention of rebleeding in combination with non-selective β blockers (NSBB). We evaluated the efficacy of pre-emptive transjugular intrahepatic portosystemic shunt (p-TIPS) in this setting.

Methods

This open-label randomised trial was conducted at 17 tertiary centres in France. Patients with cirrhosis and acute fundal variceal bleeding (excluding type 1 gastro-oesophageal varices), who achieved initial haemostasis with endoscopic glue injection and vasoactive therapy, and remained stable for at least 12 h, were randomly assigned to receive either a covered p-TIPS within 72 h or to continue with on-demand glue obliteration sessions combined with NSBB. Randomisation was centralised, stratified by centre, and performed in blocks of four (1:1 ratio). The primary composite endpoint was all-cause mortality or clinically significant rebleeding within 1 year. Analyses were conducted in the modified intention-to-treat (mITT) population. This completed study was registered on ClinicalTrials.gov (NCT03705078).

Findings

Between Jan 3, 2019, and Feb 25, 2023, 292 patients were screened, of whom 105 were enrolled and randomly assigned. After excluding two patients who were randomly assigned by error and two who withdrew consent, 101 patients were included in the mITT population (mean age 58·2 years [SD 9·7], 81 [80%] male, 91 [90%] alcohol-related cirrhosis, mean MELD score 14·3 [SD 5·0]). Of these 101 patients, 47 were allocated to p-TIPS and 54 to glue obliteration and NSBB. The 1-year probability of being free from death or rebleeding was 77% (95% CI 62–87) in the p-TIPS group versus 37% (24–50) in the glue obliteration and NSBB group (hazard ratio 0·25 [95% CI 0·12–0·51]; p<0·0001). Rescue TIPS was required in 20 (37%) patients in the control group. Glue migration was reported in eight patients (three [6%] in the p-TIPS group and five [9%] in the control group). One case of cardiac decompensation occurred in the p-TIPS group. The 1-year cumulative incidence of hepatic encephalopathy was similar between groups (35% [95% CI 21–49] vs 32% [19–45]).

Interpretation

In patients with cirrhosis and acute bleeding from fundal varices, p-TIPS significantly reduced the risk of rebleeding or death at 1 year and should be considered as first-line therapy.

Funding

French Ministry of Health.

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来源期刊

Lancet Gastroenterology & Hepatology Medicine-Hepatology

CiteScore

50.30

自引率

1.10%

发文量

期刊介绍： The Lancet Gastroenterology & Hepatology is an authoritative forum for key opinion leaders across medicine, government, and health systems to influence clinical practice, explore global policy, and inform constructive, positive change worldwide. The Lancet Gastroenterology & Hepatology publishes papers that reflect the rich variety of ongoing clinical research in these fields, especially in the areas of inflammatory bowel diseases, NAFLD and NASH, functional gastrointestinal disorders, digestive cancers, and viral hepatitis.