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

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

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1418826

DOI=10.3389/fphar.2024.1418826

ISSN=1663-9812

ABSTRACT=<sec><title>Background</title><p>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).</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>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; I<sup>2</sup> = 28%, <italic>p</italic> = 0.23; n = 6). Noradrenaline was equally effective in treatment response compared to terlipressin (RR:1.19, 95% CI:0.96 to 1.46; I<sup>2</sup> = 16%, <italic>p</italic> = 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; I<sup>2</sup> = 0%, <italic>p</italic> = 0.72; n = 3) or noradreanline (RR:0.83, 95% CI:0.69 to 1.00; I<sup>2</sup> = 4%, <italic>p</italic> = 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; I<sup>2</sup> = 0%, <italic>p</italic> = 0.75; n = 3) or noradrenaline (RR:2.45, 95% CI:1.37 to 4.37; I<sup>2</sup> = 0%, <italic>p</italic> = 0.92; n = 5).</p></sec><sec><title>Conclusion</title><p>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.</p></sec>