Wan Yue-Meng, Huang Song-Quan, Wu Hua-Mei, Li Yu-Hua, Yin Hong-Jing, Xu Ying
Gastroenterology Department II, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.
Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Front Pharmacol. 2024 Sep 4;15:1418826. doi: 10.3389/fphar.2024.1418826. eCollection 2024.
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).
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.
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 = 28%, = 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 = 16%, = 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 = 0%, = 0.72; n = 3) or noradreanline (RR:0.83, 95% CI:0.69 to 1.00; I = 4%, = 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 = 0%, = 0.75; n = 3) or noradrenaline (RR:2.45, 95% CI:1.37 to 4.37; I = 0%, = 0.92; n = 5).
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.
肝肾综合征（HRS）预后极差，目前仍缺乏安全有效的治疗方法。本系统评价和荟萃分析旨在基于既往随机对照试验（RCT），重新评估特利加压素与安慰剂或去甲肾上腺素治疗HRS的安全性和有效性。
检索PubMed、EMBASE、MEDLINE（OvidSP）和Cochrane图书馆，查找报告特利加压素或去甲肾上腺素治疗HRS的试验。检索词包括：“肝肾综合征”、“特利加压素”、“去甲肾上腺素”及相应同义词。纳入特利加压素、去甲肾上腺素、安慰剂和白蛋白之间的比较。对治疗反应（HRS逆转和完全缓解）、死亡率和不良事件进行荟萃分析。
纳入15项RCT，共1236例HRS患者（1型：1166例，2型：70例）。特利加压素联合白蛋白治疗的治疗反应显著高于安慰剂联合白蛋白或单用白蛋白（风险比[RR]：2.75，95%置信区间[CI]：1.96至3.84；I² = 28%，P = 0.23；n = 6）。与特利加压素相比，去甲肾上腺素在治疗反应方面同样有效（RR：1.19，95% CI：0.96至1.46；I² = 16%，P = 0.31；n = 7），但试验受非盲法设计和样本量小的限制。敏感性分析显示，与安慰剂（RR：1.03，95% CI：0.83至1.28；I² = 0%，P = 0.72；n = 3）或去甲肾上腺素（RR：0.83，95% CI：0.69至1.00；I² = 4%，P = 0.39；n = 7）相比，特利加压素在随访30天时未显示出生存获益。与安慰剂（RR：2.92，95% CI：1.48至5.77；I² = 0%，P = 0.75；n = 3）或去甲肾上腺素（RR：2.45，95% CI：1.37至4.37；I² = 0%，P = 0.92；n = 5）相比，特利加压素发生治疗相关不良事件的风险更高。
特利加压素在治疗反应方面优于安慰剂，与去甲肾上腺素相当，但未显示出生存获益。去甲肾上腺素虽确定性较低，但可能是治疗HRS的更好选择。
