Abstract: Background Endoscopic esophageal varices ligation (EVL) is an effective method for preventing rebleeding from esophageal variceal rupture in patients with liver cirrhosis. However, the optimal interval of EVL remains unclear. Objective To compare the effectiveness and safety of EVL at one-month and two-week intervals in preventing rebleeding in patients with liver cirrhosis. Methods Patients with liver cirrhosis complicated with acute esophageal variceal bleeding who were treated in Beijing You'an Hospital, Capital Medical University from January 2009 to October 2012 were selected as the research subjects, and randomly divided into the one-month group and the two-week group by sealed envelope method. The etiology, symptoms, physical signs, endoscopic active bleeding, gastric varices of the patients were recorded, the levels of serum albumin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and prothrombin time (PT) were detected. The severity of the disease was evaluated by Child-Pugh classification criteria, Model for End-Stage Liver Disease (MELD) and Beppu scoring system. All patients received emergency EVL within 12 hours after admission. The interval of EVL was 28 days in the one-month group and two weeks in the two-week group. The patients were followed up after operation. The primary endpoint was rebleeding, and the secondary endpoints were esophageal variceal recurrence, EVL-related adverse events and death. Results A total of 70 patients were enrolled in the study, with 35 patients in each group. There was no significant difference in the incidence of rebleeding between the two groups (P>0.05). AST level was an independent influencing factor for rebleeding after EVL in patients with liver cirrhosis 〔HR=1.02, 95%CI (1.00,1.03), P=0.012〕. There was no significant difference in the recurrence rate of esophageal varices between the two groups (P>0.05). There were no significant differences in the incidences of chest distress, retrosternal pain, dysphagia/pain between the two groups (P>0.05). The incidence of ulcer after EVL in the two-week group was higher than that in the one-month group 〔57.1% (20/35) vs. 11.4% (4/35), P<0.001〕. There was no significant difference in the mortality rate between the two groups (P>0.05). Child-Pugh classification was an influencing factor for death after EVL in patients with liver cirrhosis 〔HR=2.95, 95%CI (1.06,8.21), P=0.039〕. Conclusion EVL at one-month and two-week intervals has similar effects in preventing rebleeding, esophageal variceal recurrence and death in patients with liver cirrhosis, but the incidence of post-EVL ulcer is higher in patients receiving EVL at two-week intervals than in those receiving EVL at one-month intervals.

Key words: Esophageal and gastric varices, Endoscopic esophageal variceal ligation, Interval time, Bleeding, Recurrence, Randomized controlled trial

摘要： 背景 内镜下食管静脉曲张套扎术（EVL）为有效预防肝硬化食管静脉曲张破裂再出血的方法。然而，最佳 EVL 间隔时间仍不清楚。目的 比较间隔 1 个月和两周行 EVL 预防肝硬化患者再出血的有效性和安全性。方法 选取 2009 年 1 月 —2012 年 10 月于首都医科大学附属北京佑安医院治疗的肝硬化急性食管静脉曲张破裂出血患者为研究对象，采用密闭信封法随机分为每月组和两周组。记录患者病因、症状、体征、内镜下活动性出血、胃底静脉曲张情况，检测静脉血清蛋白、总胆红素、天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）水平及凝血酶原时间，采用 Child-Pugh 分级标准、终末期肝病模型（MELD）和 Beppu 评分系统评价患者疾病严重程度。患者入院 12 h 内行急诊 EVL 治疗，每月组行 EVL 的间隔时间为 28 d，两周组行 EVL 的间隔时间为两周。术后对患者进行随访，主要终点是再出血，次要终点是食管静脉曲张复发、EVL 相关不良事件和死亡。结果 本研究共入选 70 例患者，两组各 35 例。两组再出血发生率比较，差异无统计学意义（P>0.05）。AST 水平是肝硬化患者 EVL 后再出血的独立影响因素〔HR=1.02，95% CI（1.00，1.03），P=0.012〕。两组食管静脉曲张复发率比较，差异无统计学意义（P>0.05）。两组胸闷、胸骨后疼痛、吞咽困难 / 疼痛发生率比较，差异均无统计学意义（P>0.05）。两周组 EVL 后溃疡发生率高于每月组〔57.1%（20/35）与 11.4%（4/35），P<0.001〕。两组患者病死率比较，差异无统计学意义（P>0.05）。Child-Pugh 分级是肝硬化患者 EVL 后死亡的影响因素〔HR=2.95，95% CI（1.06，8.21），P=0.039〕。结论 EVL 间隔时间为 1 个月和两周在预防肝硬化患者再出血、食管静脉曲张复发及死亡方面效果相当，但间隔两周行 EVL 的患者 EVL 后溃疡的发生率高于间隔时间为 1 个月的患者。

关键词: 食管和胃静脉曲张, 内镜下食管静脉曲张套扎术, 间隔时间, 出血, 复发, 随机对照试验