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SYSTEMATIC REVIEW article

Front. Pharmacol.
Sec. Renal Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1418826

Terlipressin versus Placebo or Noradrenalin in the Treatment of Hepatorenal Syndrome: A Systematic Review and Meta-Analysis

Provisionally accepted
Yue-Meng Wan Yue-Meng Wan *Song-Quan Huang Song-Quan Huang Hua-Mei Wu Hua-Mei Wu Yu-Hua Li Yu-Hua Li Hong-Jing Yin Hong-Jing Yin Ying Xu Ying Xu
  • Kunming Medical University, Kunming, China

The final, formatted version of the article will be published soon.

    Abstract Background: Hepatorenal syndrome (HRS) bears a very poor prognosis with unmet need for safe and effective therapies. This systematic review and meta-analysis aimed to re-assess safety and efficacy of terlipressin versus placebo or noradrenaline for HRS, based on previous randomized controlled trials (RCTs). Methods: PubMed, EMBASE, MEDLINE (OvidSP) and Cochrane registers were searched for trials reporting HRS treatment by terlipressin or noradrenaline. Search terms included: ‘hepatorenal syndrome’, ‘terlipressin’, ‘noradrenaline’, and corresponding synonyms. Comparisons between terlipressin, noradreanaline, placebo and albumin were included. Meta-analysis was conducted for treatment response (both HRS reversal and complete response), mortality and adverse events. Results: 15 RCTs were included, enrolling 1236 HRS patients (type 1: 1166, type 2: 70). Treatment with terlipressin+albumin resulted in significantly higher treatment response than placebo+albumin or albumin alone (risk ratio[RR]:2.75, 95% confidence interval[CI]:1.96 to 3.84; I2=28%, P=0.23; n=6). Noradrenaline was equally effective in treatment response compared to terlipressin (RR:1.19, 95% CI:0.96 to 1.46; I2=16%, P=0.31; n=7), but trials were limited by its non-blind design and small size. Sensitivity analysis showed no survival benefit with terlipressin compared to either placebo (RR:1.03, 95% CI:0.83 to 1.28; I2=0%, P=0.72; n=3) or noradreanline (RR:0.83, 95% CI:0.69 to 1.00; I2=4%, P=0.39; n=7) at 30 days of follow-up. Terlipressin carried higher risk of treatment-related adverse events compared to either placebo (RR:2.92, 95% CI:1.48 to 5.77; I2=0%, P=0.75; n=3) or noradrenaline (RR:2.45, 95% CI:1.37 to 4.37; I2=0%, P=0.92; n=5). Conclusion: Terlipressin is superior to placebo, and comparable to noradreanline in treatment response, but survival benefit is lacking. Noradrenaline, with low certainty, may be a better alternative for HRS.

    Keywords: AEs, Adverse events, AKI, acute kidney injury, ALB, albumin, CIs, Confidence intervals, CIV, continuous intravenous infusion, Ctl, comparator group, CTP, child-turcotte-pugh, EOT, end of treatment

    Received: 19 Apr 2024; Accepted: 27 Aug 2024.

    Copyright: © 2024 Wan, Huang, Wu, Li, Yin and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yue-Meng Wan, Kunming Medical University, Kunming, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.