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肝肾综合征-急性肾损伤的当前药物治疗方法。

Current Pharmacologic Therapies for Hepatorenal Syndrome-Acute Kidney Injury.

机构信息

Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia.

Division of Pharmacy, Virginia Commonwealth University Health, Richmond, Virginia.

出版信息

Clin Gastroenterol Hepatol. 2023 Sep;21(10S):S27-S34. doi: 10.1016/j.cgh.2023.06.006.

Abstract

BACKGROUND & AIMS: Hepatorenal syndrome (HRS) can occur in patients with cirrhosis and ascites due to splanchnic vasodilation, renal hypoperfusion, and vasoconstriction. HRS is a diagnosis of exclusion and portends a poor prognosis, with upward of 80% mortality at 2 weeks without treatment. This review will highlight randomized controlled trials for HRS pharmacotherapy.

METHODS

A PubMed review of randomized controlled trials conducted over the past 25 years was undertaken; 18 studies were included.

RESULTS

Initial studies showed that norepinephrine is as effective as terlipressin for HRS reversal. Midodrine with octreotide and albumin is less effective than terlipressin but better than albumin alone at improving 30-day mortality. Recently, terlipressin with albumin led to significantly higher rates of HRS reversal compared to albumin alone. Non-response to terlipressin can predict 90-day mortality in acute-on-chronic-liver failure.

CONCLUSIONS

Our current understanding of HRS treatment is improved by recent randomized clinical trials. Previous studies using varying medication doses along with the "old" definition of hepatorenal syndrome (HRS type 1) rather than HRS-AKI means that there is still a need for future multicenter prospective studies further refining the risk-benefit ratio of vasoconstrictors for HRS-AKI patients. The Food and Drug Administration has approved terlipressin for use in September 2022. Because it will take time to adapt into clinical practice, less cost-prohibitive vasoconstrictors should still be considered. Opportunities also exist to clarify the safety, timing of initiation, as well as possible discontinuation of terlipressin.

摘要

背景与目的

肝性肾综合征(HRS)可发生于肝硬化伴腹水患者,其发病机制为内脏血管扩张、肾灌注减少和血管收缩。HRS 的诊断为排他性诊断,预示预后不良,未经治疗者 2 周病死率超过 80%。本综述将重点介绍 HRS 药物治疗的随机对照试验。

方法

对过去 25 年开展的随机对照试验进行了 PubMed 综述,共纳入 18 项研究。

结果

最初的研究表明,去甲肾上腺素治疗 HRS 逆转的疗效与特利加压素相当。米多君联合奥曲肽和白蛋白的疗效不如特利加压素,但优于白蛋白单药治疗,可降低 30 天死亡率。最近,特利加压素联合白蛋白可显著提高 HRS 逆转率,优于白蛋白单药治疗。特利加压素治疗无应答可预测慢加急性肝衰竭患者 90 天死亡率。

结论

近期的随机临床试验改善了我们对 HRS 治疗的认识。以前的研究使用了不同的药物剂量,以及“旧”的肝性肾综合征(HRS 1 型)定义,而非 HRS-AKI,这意味着仍需要进一步开展多中心前瞻性研究,以明确血管收缩剂治疗 HRS-AKI 患者的风险效益比。特利加压素于 2022 年 9 月获得美国食品和药物管理局批准用于临床。由于需要时间来适应临床实践,因此仍应考虑使用成本效益更高的血管收缩剂。目前也有机会进一步阐明特利加压素的安全性、起始时机以及可能的停药时间。

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