Rattanasupar Attapon, Chang Arunchai, Akarapatima Keerati, Chaojin Thanongsak, Piratvisuth Teerha
Division of Gastroenterology, Department of Internal Medicine, Hatyai Hospital, 182 Ratthakanl Road, Hatyai, Songkhla, 90110, Thailand.
Division of Gastroenterology, Department of Internal Medicine, Yala Hospital, Yala, Thailand.
Indian J Gastroenterol. 2021 Dec;40(6):621-629. doi: 10.1007/s12664-021-01150-2. Epub 2021 Jun 15.
We aimed to assess the efficacy of lactulose as prophylaxis against hepatic encephalopathy (HE) in cirrhotic patients with acute upper gastrointestinal bleeding (AUGIB).
We conducted a randomized, double-blinded, placebo-controlled, multicenter study from October 2012 to February 2014. Cirrhotic patients presenting with AUGIB (aged 18-80 years, without HE at the time of admission) were enrolled and randomized to receive blinded medications (both physically indistinguishable), labeled "Lactulose A" and "Lactulose B" for 5 days along with standard treatment depending on the type of bleeding (variceal and nonvariceal). The primary endpoint was the development of overt HE according to the West-Haven criteria. Modified intention-to-treat analysis was performed.
Forty-six patients completed the protocol: Lactulose A (placebo, n = 22) and Lactulose B (lactulose, n = 24). There was no significant difference in baseline characteristics and clinical outcomes between the two groups. Nine (19.6%) patients developed HE: five (22.7%) in the placebo group and four (16.7%) in the lactulose group (p = 0.718). One patient (2.2%) died in lactulose group. All patients tolerated the medication and no significant difference in adverse effects was detected (59.1% in placebo vs. 50.0% in lactulose group, p = 0.536). On multivariate analysis, increased baseline Child-Turcotte-Pugh (CTP) score (odds ratio [OR] 2.176; 95% confidence interval [CI] 1.012-4.681, p = 0.047) and presence of diarrhea (OR 16.261; 95% CI 1.395-189.608, p = 0.026) were independent risk factors for the development of HE.
Five-day lactulose is ineffective as prophylaxis against HE in cirrhotic patients with AUGIB. Unnecessary treatment with laxatives should be avoided in these patients.
Clinical trial registry number TCTR20200526003 (retrospectively registered).
我们旨在评估乳果糖对肝硬化合并急性上消化道出血（AUGIB）患者预防肝性脑病（HE）的疗效。
我们于2012年10月至2014年2月开展了一项随机、双盲、安慰剂对照、多中心研究。纳入出现AUGIB的肝硬化患者（年龄18 - 80岁，入院时无HE），随机接受盲法用药（两者外观无法区分），标记为“乳果糖A”和“乳果糖B”，持续5天，并根据出血类型（静脉曲张出血和非静脉曲张出血）给予标准治疗。主要终点是根据West - Haven标准判断显性HE的发生情况。进行了改良意向性分析。
46例患者完成了方案：乳果糖A组（安慰剂，n = 22）和乳果糖B组（乳果糖，n = 24）。两组间基线特征和临床结局无显著差异。9例（19.6%）患者发生HE：安慰剂组5例（22.7%），乳果糖组4例（16.7%）（p = 0.718）。乳果糖组1例患者（2.2%）死亡。所有患者均耐受用药，未检测到不良反应有显著差异（安慰剂组59.1%，乳果糖组50.0%，p = 0.536）。多因素分析显示，基线Child - Turcotte - Pugh（CTP）评分升高（比值比[OR] 2.176；95%置信区间[CI] 1.012 - 4.681，p = 0.047）和腹泻的存在（OR 16.261；95% CI 1.395 - 189.608，p = 0.026）是HE发生的独立危险因素。
对于肝硬化合并AUGIB的患者，5天的乳果糖预防HE无效。应避免对这些患者进行不必要的泻药治疗。
临床试验注册号TCTR20200526003（回顾性注册）
