Document Type

Article

Publication Date

12-10-2024

Comments

This article is the author's final published version in JGH Open, Volume 8, Issue 12, December 2024, Article number e70058.

The published version is available at https://doi.org/10.1002/jgh3.70058.

Copyright © 2024 The Author(s)

Abstract

INTRODUCTION: The degree of improvement in serum creatinine (SCr) has previously been suggested as a sensitive indicator of treatment response in patients with hepatorenal syndrome-acute kidney injury (HRS-AKI), while HRS reversal remains the primary endpoint in clinical trials.

METHODS: A total of ≥ 30% SCr improvement was analyzed as an exploratory prespecified endpoint in the CONFIRM trial. In this post hoc analysis, intent-to-treat population data from three Phase 3 studies (OT-0401, REVERSE, and CONFIRM) conducted in North America in patients with HRS-AKI were pooled to assess the incidence of > 30% improvement in SCr and its association with clinical outcomes.

RESULTS: Significantly more patients treated with terlipressin achieved > 30% improvement in SCr compared with those who received a placebo (42.9% vs. 23.4%; p < 0.001). Compared with patients who did not achieve > 30% improvement in SCr, those who achieved this threshold had a lower incidence of renal replacement therapy (RRT) (55.2% vs. 14%, respectively; p < 0.001) and greater overall survival at Day 90 (41.6% vs. 71.1%, respectively; p < 0.001); a greater proportion achieved durability of HRS reversal (1% [95% confidence interval, 95% CI: 0] vs. 68.9% [95% CI: 0.6, 0.8]) and more patients were alive without RRT (22.7% vs. 61.6%, respectively; p < 0.001) or transplant (11.6% vs. 43.0%, respectively; p < 0.0001). Additionally, the overall survival and RRT-free survival in the group that achieved > 30% improvement in SCr without HRS reversal were comparable to the overall
group that achieved HRS reversal.

CONCLUSION: A total of > 30% improvement in SCr levels even without HRS reversal may serve as a clinically meaningful endpoint to define renal recovery in patients with HRS-AKI.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Language

English

PubMed ID

39664961

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