Singal Ashwani K, Palmer Geralyn, Melick Lauren, Abdallah Mohamed, Kwo Paul
Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, South Dakota.
Transplant Hepatology, Avera Transplant Institute, Sioux Falls, South Dakota.
Gastro Hep Adv. 2023 Jan 18;2(4):455-464. doi: 10.1016/j.gastha.2023.01.007. eCollection 2023.
Type 1 hepatorenal syndrome (HRS) is a rapid deterioration in kidney function in patients with cirrhosis. Data on efficacy of vasoconstrictors for type 1 HRS have shown mixed results.
Literature searched for randomized controlled trials comparing pharmacological therapy for HRS vs placebo or another drug for HRS. Primary outcome was HRS reversal (serum creatinine <1.5mg/dL on 2 readings), and secondary outcomes were liver transplant (LT) free survival and serious adverse events (SAE).
Sixteen studies on 1244 patients (mean age 50.3 yrs., 67.5% males, serum creatinine of 3.07 mg/dL, serum sodium 127.2 mEq/liter, and Model for End-stage Liver Disease (MELD) score of 30.9, and Child-Pugh score 11) with type 1 HRS treated with vasoconstrictors vs placebo or another drug were analyzed. All the patients received intravenous albumin infusion. (A) terlipressin vs placebo: Odds of HRS reversal were 3.3 folds with terlipressin without difference on LT-free patient survival. Terlipressin was associated with higher odds of SAE. (B) Nor-epinephrine (NE) vs terlipressin: No difference on HRS reversal, LT-free survival, and SAE. (C) Terlipressin or NE vs midodrine and octreotide: 91% lower odds of HRS reversal with midodrine and octreotide. There were no differences on SAE (10 of 64 vs 10 of 58, = .812). Non-responders vs responders had higher mean MELD score (29 vs 27.8), = .014 and serum creatinine (3.5 vs 3.1), = .027.
Terlipressin and NE are similar and superior to midodrine octreotide combination for HRS reversal. No therapy improves LT-free patient survival. Response to treatment is better with lower baseline serum creatinine and MELD score. The risk of adverse effects is similar with terlipressin and NE. Studies are needed as basis to identify candidates with best response to treatment with excellent safety profile.
1型肝肾综合征（HRS）是肝硬化患者肾功能的快速恶化。血管收缩剂治疗1型HRS的疗效数据显示结果不一。
检索比较HRS药物治疗与安慰剂或其他治疗HRS药物的随机对照试验的文献。主要结局是HRS逆转（两次读数时血清肌酐<1.5mg/dL），次要结局是无肝移植（LT）生存期和严重不良事件（SAE）。
分析了16项关于1244例1型HRS患者（平均年龄50.3岁，67.5%为男性，血清肌酐3.07mg/dL，血清钠127.2mEq/升，终末期肝病模型（MELD）评分30.9，Child-Pugh评分11）使用血管收缩剂与安慰剂或其他药物治疗的研究。所有患者均接受静脉输注白蛋白。（A）特利加压素与安慰剂：特利加压素使HRS逆转的几率为3.3倍，在无肝移植患者生存期方面无差异。特利加压素与更高的SAE几率相关。（B）去甲肾上腺素（NE）与特利加压素：在HRS逆转、无肝移植生存期和SAE方面无差异。（C）特利加压素或NE与米多君和奥曲肽：米多君和奥曲肽使HRS逆转的几率降低了91%。SAE方面无差异（64例中有10例，58例中有10例，P = 0.812）。无反应者与有反应者相比，平均MELD评分更高（29对vs 27.8），P = 0.014，血清肌酐更高（3.5对3.1），P = 0.027。
特利加压素和NE在HRS逆转方面相似且优于米多君和奥曲肽联合用药。没有治疗方法能改善无肝移植患者的生存期。基线血清肌酐和MELD评分较低时对治疗的反应更好。特利加压素和NE的不良反应风险相似。需要开展研究，以便确定对治疗反应最佳且安全性良好的候选者。
