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失代偿期肝硬化各临床分期进一步失代偿对生存的影响:门静脉高压和 HVPG 变化的作用。

Influence of further decompensation on survival across clinical stages of decompensated cirrhosis: The role of portal hypertension and HVPG changes.

机构信息

Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Universitat Autònoma de Barcelona, Barcelona, Spain.

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.

出版信息

Liver Int. 2024 Aug;44(8):1971-1989. doi: 10.1111/liv.15937. Epub 2024 Apr 18.

Abstract

BACKGROUND AND AIMS

Decompensated-cirrhosis encompasses several stages with different prognosis, such as bleeding, ascites and bleeding-plus-ascites. Development of further-decompensation worsens survival, while non-selective β-blockers (NSBBs) can modify the risk. However, how this applies to each stage is uncertain. We aimed to investigate, in each stage of decompensated-cirrhosis, the influence of further-decompensation on mortality and whether changes in portal-pressure (HVPG) under NSBBs influence these outcomes.

METHODS

Patients with variceal bleeding were consecutively included differentiating those with bleeding-alone from those who also had ascites. Patients with ascites and high-risk varices referred for primary-prophylaxis were also investigated. A baseline haemodynamic study was performed and was repeated after 1-3-months under NSBBs. Outcomes were investigated by competing-risk.

RESULTS

Totally 103 patients had bleeding-alone, 186 bleeding-plus-ascites and 187 ascites-alone. Mean follow-up was 32-months (IQR, 12-60). Patients with bleeding-plus-ascites had higher HVPG and were more hyperdynamic than patients with ascites-alone and these than those with bleeding-alone. At each stage, the mortality risk was more than twice in patients developing further-decompensation vs. those without (p < .001). In each stage, HVPG-decrease under NSBBs showed better discrimination to predict further-decompensation than the baseline MELD, Child-Pugh or HVPG, by time-dependent ROC-curves (c-statistic >70%). At each stage, patients without HVPG-decreases, either ≥10% or ≥20% from the baseline, had higher risk of further-decompensation (sHR from 2.43 to 6.73, p < .01) and worse survival.

CONCLUSIONS

In each stage of decompensated cirrhosis, mortality risk significantly and very markedly increase with further-decompensation. HVPG-non-response to NSBBs may adequately stratify the risk of further decompensation and death, in each stage. This suggests potential benefit with pre-emptive therapies in HVPG-non-responders at each-stage.

摘要

背景与目的

失代偿期肝硬化包括不同预后的几个阶段,如出血、腹水和出血伴腹水。进一步失代偿的发展会降低生存率,而非选择性β受体阻滞剂(NSBBs)可改变这种风险。然而,这种情况在每个阶段的应用尚不确定。我们旨在研究失代偿期肝硬化的每个阶段,进一步失代偿对死亡率的影响,以及 NSBBs 下门静脉压力(HVPG)的变化是否会影响这些结果。

方法

连续纳入静脉曲张出血患者,区分仅出血患者和同时有腹水的患者。还对有腹水和高危静脉曲张并接受一级预防的患者进行了调查。进行基线血流动力学研究,并在 1-3 个月后在 NSBBs 下重复。通过竞争风险进行结果研究。

结果

共有 103 例仅出血、186 例出血伴腹水和 187 例仅腹水。平均随访时间为 32 个月(IQR,12-60)。出血伴腹水的患者 HVPG 更高,比仅腹水患者更具高动力性,而后者比仅出血患者更具高动力性。在每个阶段,与无进一步失代偿的患者相比,发展为进一步失代偿的患者的死亡率风险增加了一倍以上(p<0.001)。在每个阶段,与基线 MELD、Child-Pugh 或 HVPG 相比,NSBBs 下 HVPG 下降通过时间依赖性 ROC 曲线(c 统计量>70%)更好地预测进一步失代偿(c 统计量>70%)。在每个阶段,HVPG 下降<10%或<20%的患者,进一步失代偿的风险更高(风险比从 2.43 到 6.73,p<0.01),生存情况更差。

结论

在失代偿期肝硬化的每个阶段,死亡率风险随着进一步失代偿显著且非常显著地增加。NSBBs 对 HVPG 无反应可能足以分层每个阶段进一步失代偿和死亡的风险。这表明在每个阶段对 HVPG 无反应者进行抢先治疗可能会有潜在益处。

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