INTRODUCTION Critically ill cirrhosis (CIC) patients admitted to the intensive care unit (ICU) are usually on broad-spectrum antibiotics due to suspected infection or as a hospital protocol. It is unclear if additional rifaximin has any synergistic effect with broad-spectrum antibiotics in ICU patients with acute overt hepatic encephalopathy (OHE). METHODS In this double-blind trial, patients with OHE admitted to ICU were randomized to receive antibiotics (ab) alone or antibiotics with rifaximin (ab+r). Resolution (or 2 grade reduction) of HE, time to resolution of HE, in-hospital mortality, nosocomial infection, and changes in endotoxin levels were compared between the two groups. Sub-group analysis of patients with decompensated cirrhosis (DC) and acute-on-chronic liver failure (ACLF) was performed. RESULTS Baseline characteristics and severity scores were similar among both groups (92 in each group). Carbapenems and cephalosporin with beta-lactamase inhibitors were the most commonly used antibiotics. On Kaplan-Meier analysis 44.6% (41/92; 95% CI, 32-70.5) in antibiotics only arm and 46.7% (43/92; 95%CI, 33.8-63) in antibiotics+rifaximin arm achieved the primary objective (P=0.84).Time to achieve the primary objective (3.65±1.82 days and 4.11±2.01 days; P=0.27) and in-hospital mortality were similar among both groups (62% vs. 50%;P=0.13). Seven percent and 13% in the ab and ab+r groups developed nosocomial infections (P=0.21). Endotoxin levels were unaffected by rifaximin. Rifaximin led to lower in-hospital mortality (HR: 0.39 [95%CI,0.2-0.76]) in patients with DC but not in patients with ACLF (HR: 0.99 [95%CI,0.6-1.63]) due to reduced nosocomial infections. DISCUSSION Reversal of overt HE in those on antibiotics was comparable to those on antibiotics+rifaximin.

中文翻译：

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抗生素联合或不联合利福昔明治疗肝硬化危重患者的急性肝性脑病：一项双盲、随机对照 (ARiE) 试验。

简介 入住重症监护病房 (ICU) 的危重肝硬化 (CIC) 患者通常因疑似感染或作为医院方案而使用广谱抗生素。目前尚不清楚额外的利福昔明与广谱抗生素对 ICU 急性明显肝性脑病 (OHE) 患者是否具有协同作用。方法 在这项双盲试验中，入住 ICU 的 OHE 患者被随机分配接受单独抗生素 (ab) 或抗生素联合利福昔明 (ab+r) 治疗。比较两组间 HE 的缓解（或 2 级降低）、HE 缓解的时间、院内死亡率、医院感染和内毒素水平的变化。对失代偿性肝硬化（DC）和慢加急性肝衰竭（ACLF）患者进行亚组分析。结果 两组的基线特征和严重程度评分相似（每组 92 分）。碳青霉烯类和头孢菌素与β-内酰胺酶抑制剂是最常用的抗生素。根据 Kaplan-Meier 分析，仅使用抗生素组的 44.6%（41/92；95% CI，32-70.5）和抗生素+利福昔明组的 46.7%（43/92；95% CI，33.8-63）实现了主要目标（ P=0.84）。两组实现主要目标的时间（3.65±1.82 天和 4.11±2.01 天；P=0.27）和院内死亡率相似（62% vs. 50%；P=0.13）。ab 组和 ab+r 组中分别有 7% 和 13% 发生院内感染（P=0.21）。内毒素水平不受利福昔明的影响。利福昔明可降低 DC 患者的院内死亡率（HR：0.39 [95% CI，0.2-0.76]），但不会降低 ACLF 患者的院内死亡率（HR：0.99 [95% CI，0.6-1.63]），因为院内死亡率降低感染。讨论 抗生素组明显 HE 的逆转与抗生素+利福昔明组相当。