Terlipressin versus placebo or noradrenalin in the treatment of hepatorenal syndrome: a systematic review and meta-analysis

Yue-Meng Wan; Song-Quan Huang; Hua-Mei Wu; Yu-Hua Li; Hong-Jing Yin; Ying Xu

doi:10.3389/fphar.2024.1418826

Terlipressin versus placebo or noradrenalin in the treatment of hepatorenal syndrome: a systematic review and meta-analysis

Front Pharmacol. 2024 Sep 4:15:1418826. doi: 10.3389/fphar.2024.1418826. eCollection 2024.

Authors

Yue-Meng Wan¹, Song-Quan Huang², Hua-Mei Wu¹, Yu-Hua Li¹, Hong-Jing Yin¹, Ying Xu¹

Affiliations

¹ Gastroenterology Department II, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.
² Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

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: hepatorenal syndrome; noradrenaline; survival; terlipressin; treatment response; vasoactive drugs.

Publication types

Systematic Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was funded by China Scholarship Council (No. 202108530150).