A randomized, controlled trial of banding ligation plus drug therapy versus drug therapy alone in the prevention of esophageal variceal rebleeding

Background & Aims:  Both medications with beta-blockers and isosorbide-5-mononitrate and endoscopic variceal ligation have been proven plausible in the prevention of variceal rebleeding. However, the relative efficacy and safety of the combined treatment for preventing rebleeding remains unresolved.
Methods:  Patients with history of esophageal variceal bleeding were enrolled. Emergency ligation was performed in patients with acute variceal bleeding. After hemodynamic stability, eligible patients were randomized to either the Medication group, using nadolol plus isorsorbide-5-mononitrate, or the Combined group, receiving banding ligation in addition to medications. Patients in the two groups with rebleeding from esophageal varices were treated with band ligation. The end points were rebleeding from varices or death.
Results:  After a median follow up of 23 months, recurrent upper gastrointestinal bleeding developed in 51% in the Medication group and 38% in the Combined group ( P  = 0.21). Recurrent bleeding from esophageal varices occurred in 26 patients (43%) in the Medication group and in 16 patients (26%) in the Combined group ( P  = 0.07). Recurrent bleeding from gastroesophageal varices occurred in 48% of Medication group and 28% of Combined group ( P  = 0.05). The frequency of adverse effects and mortality rates were similar between both groups ( P  = 0.28).
Conclusions:  Combined ligation with medications was marginally more effective than medication alone in the prevention of gastroesophageal variceal rebleeding with similar adverse effects and mortality.     

A randomized,controlled trial of medical therapy versus endoscopic ligation for the prevention of variceal rebleeding in patients with cirrhosis

BACKGROUND & AIMS: Patients who have had one variceal bleed are at high risk of rebleeding. Since its introduction, endoscopic variceal banding has been shown to be superior to needle sclerotherapy. Banding has not been compared with hepatic venous pressure-guided medical therapy (beta-blockers and nitrates). METHODS: One hundred two patients with cirrhosis and a recent esophageal variceal bleed were randomized to either endoscopic banding (51 patients) or medical therapy (51 patients). The hepatic venous pressure gradient was measured in all patients at baseline, at 3 months (drug therapy arm), and at yearly intervals (all patients). Primary end points were death or rebleeding. RESULTS: The 2 groups were well matched. Fifty-one percent were Pughs C, with a median Pughs score of 9.5. Nineteen patients rebled in the drug arm (median time, 24 days) and 27 patients in the banding arm (median time, 24 days). At 1 year, 43.7% of patients had bled in the drug arm compared with 53.8% in the banding arm (P = 0.25). Thirty-two percent of patients on medical therapy had died at 1 year, 22.5% on banding (P = 0.97). CONCLUSIONS: In the prevention of variceal rebleeding, beta-blockers +/- nitrates are as effective as endoscopic banding.     

Banding ligation versus nadolol and isosorbide mononitrate for the prevention of esophageal variceal rebleeding

BACKGROUND & AIMS: beta-blockers and banding ligation are effective in the prevention of variceal rebleeding. However, the relative efficacy and safety remains unresolved. METHODS: One hundred twenty-one patients with a history of esophageal variceal bleeding were enrolled. Patients were randomized to undergo regular endoscopic variceal ligation (EVL group, 60 patients) until variceal obliteration, or drug therapy by using nadolol plus isosorbide mononitrate (N+I group, 61 patients) during the study period to prevent rebleeding. RESULTS: After a median follow-up period of 25 months, recurrent upper gastrointestinal bleeding developed in 23 patients in the EVL group and 35 patients in the N+I group (P = 0.10). Recurrent bleeding from esophageal varices occurred in 12 patients (20%) in the EVL group and 26 patients (42%) in the N+I group (relative risk = 0.45; 95% confidence interval, 0.24-0.85). The actuarial probability of rebleeding from esophageal varices was lower in the EVL group (P = 0.01). The multivariate Cox analysis indicated that the treatment was the only factor predictive of rebleeding. Treatment failure occurred in 8 patients (13%) in the EVL group and 17 patients (28%) in the N+I group (P = 0.01). Fifteen patients in the EVL group and 8 patients of the N+I group died (P = 0.06). Complications occurred in 17% of the EVL group and in 19% of the N+I group (P = 0.6). CONCLUSIONS: Our trial showed that ligation was more effective than nadolol plus isosorbide-5-mononitrate in the prevention of variceal rebleeding, with similar complications in both treatment modalities. However, there is no significant difference in the survival rate between the 2 groups.     

Adding banding ligation is effective as rescue therapy to prevent variceal rebleeding in haemodynamic non-responders to pharmacological therapy

Background

It is unknown which is the best therapy to treat haemodynamic non-responders to pharmacological therapy after variceal bleeding.

Aim

To evaluate the efficacy of adding banding ligation to drugs to prevent variceal rebleeding in haemodynamic non-responders to drugs.

Methods

Fifty-three cirrhotic patients with variceal bleeding underwent a hepatic venous pressure gradient (HVPG) measurement 5 days after the episode. Nadolol and nitrates were then titrated to maximum tolerated doses. A second HVPG was taken 14 days later. Responders (HVPG ≤12 mm Hg or ≥20% decrease from baseline) were maintained on drugs and non-responders had banding ligation added to drugs.

Results

Mean follow-up was 28 months. In 5 patients the second HVPG could not be performed because of early rebleeding. The remaining 48 patients were classified as responders (n = 24) and non-responders (n = 24), who had banding added. No baseline differences were observed between groups. Variceal rebleeding occurred in 12% of the 48 patients whose haemodynamic response was assessed. Responders on drug therapy presented a 16% rebleeding rate, whilst non-responders rescued with banding showed an 8% rebleeding rate. Rebleeding-related mortality was not different between groups.

Conclusion

In a HVPG-guided strategy, adding banding ligation to drugs is an effective rescue strategy to prevent rebleeding in haemodynamic non-responders to drug therapy.     

Endoscopic variceal ligation plus nadolol and sucralfate compared with ligation alone for the prevention of variceal rebleeding: a prospective, randomized trial

Both beta-blockers and endoscopic variceal ligation (EVL) have proven to be valuable alternatives to sclerotherapy in the prevention of variceal rebleeding. Sucralfate is a mucosal protector. The effects of combinations of beta-blocker, band ligation, and sucralfate (triple therapy) remain unknown. A total of 122 patients with a history of esophageal variceal bleeding were randomized to receive EVL only (group A, 62 patients) or triple therapy (group B, 60 patients). The procedure for the triple therapy included ligation with the addition of sucralfate granules until variceal obliteration. In addition, nadolol was administered during the course of the study or until death. After a median follow-up of 21 months, recurrent upper gastrointestinal bleeding developed in 29 patients (47%) in group A and 14 patients (23%) in group B (P =.005). Recurrent bleeding from esophagogastric varices occurred in 18 patients in group A and 7 patients in group B (P =.001). Twenty-one patients in group A (50%) and 12 patients (26%) in group B experienced variceal recurrence after variceal obliteration (P <.05). Treatment failure occurred in 11 patients (18%) in group A and in 4 patients (7%) in group B (P =.05). Twenty patients from group A and 10 patients from group B died (P =.08); 9 and 4 of these deaths, respectively, were attributed to variceal hemorrhage (P =.26). The combination of ligation, nadolol, and sucralfate (triple therapy) proved more effective than banding ligation alone in terms of prevention of variceal recurrence and upper gastrointestinal rebleeding as well as variceal rebleeding.     

食管静脉曲张出血套扎术后再出血的预防及治疗

食管静脉曲张出血是肝硬化失代偿期最常见也是最严重的并发症,发病率和病死率较高.套扎术能有效治疗食管静脉曲张,但术后的再出血率很高.因此,预防套扎术后的再出血,是提高肝硬化患者生存率的重要措施.随着人们对套扎术后患者再出血的预防及治疗研究的不断进展,有助于改善肝硬化这一严重并发症的结局.目前已经开展了许多预防再出血的治疗方法,包括内镜或手术治疗、药物治疗,以及联合治疗方法.关于单一方法治疗或联合治疗的效果,已有多项试验进行了研究,本文将对以上研究成果进行综述,以指导临床选择适宜的预防和治疗策略.     

心得安联合内镜套扎术预防食管静脉曲张再出血的疗效分析

目的比较心得安联合内镜套扎治疗与单独内镜套扎治疗预防食管静脉曲张再出血的疗效。方法 65例食管静脉曲张破裂出血的患者随机分为心得安联合内镜套扎治疗组(33例),单独内镜套扎治疗组(32例),平均随访12个月,比较两组间再出血率,门脉高压性胃病,食管静脉曲张复发和胃底静脉曲张的发生率。结果两组治疗后随访第6,12个月显示,与单独内镜套扎治疗比较,心得安联合内镜套扎治疗显著降低再出血率(15.2%vs 37.5%,21.2%vs 46.9%,P<0.05),门脉高压性胃病(18.2%vs43.8%,30.3%vs 56.3%,P<0.05),食管静脉曲张复发(15.2%vs 37.5%,24.2%vs 50.0%,P<0.05)和胃底静脉曲张的发生率(12.1%vs 34.4%,21.2%vs 46.9%,P<0.05)。结论心得安联合内镜套扎治疗是二级预防食管静脉曲张出血的首选治疗方法。     

Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal rebleeding: a multicenter trial

beta-Blockers and endoscopic variceal ligation (EVL) have proven to be valuable methods in the prevention of variceal rebleeding. The aim of this study was to compare the efficacy of EVL combined with nadolol versus EVL alone as secondary prophylaxis for variceal bleeding. Patients admitted for acute variceal bleeding were treated during emergency endoscopy with EVL or sclerotherapy and received somatostatin for 5 days. At that point, patients were randomized to receive EVL plus nadolol or EVL alone. EVL sessions were repeated every 10 to 12 days until the varices were eradicated. Eighty patients with cirrhosis (alcoholic origin in 66%) were included (Child-Turcotte-Pugh A, 15%; B, 56%; C, 29%). The median follow-up period was 16 months (range, 1-24 months). The variceal bleeding recurrence rate was 14% in the EVL plus nadolol group and 38% in the EVL group (P = .006). Mortality was similar in both groups: five patients (11.6%) died in the combined therapy group and four patients (10.8%) died in the EVL group. There were no significant differences in the number of EVL sessions to eradicate varices: 3.2 +/- 1.3 in the combined therapy group versus 3.5 +/- 1.3 in the EVL alone group. The actuarial probability of variceal recurrence at 1 year was lower in the EVL plus nadolol group (54%) than in the EVL group (77%; P = .06). Adverse effects resulting from nadolol were observed in 11% of the patients. In conclusion, nadolol plus EVL reduces the incidence of variceal rebleeding compared with EVL alone. A combined treatment could lower the probability of variceal recurrence after eradication.     

内镜下套扎术预防晚期血吸虫病食管静脉曲张破裂出血

目的 目的 探讨内镜下套扎术预防晚期血吸虫病 （晚血） 食管静脉曲张再发和破裂出血的作用。方法 方法 治疗组为42 例套扎术后晚血患者, 对照组为同期住院不愿接受套扎治疗的30例晚血患者, 治疗期间3～6个月复查胃镜1次, 了解食管 静脉曲张情况, 并记录有关医疗事件。 结果 结果 套扎治疗后随访2～3年, 平均29个月。治疗组静脉曲张复发8例, 复发率 19.0%, 平均复发时间30个月; 发生食管静脉曲张破裂出血5例, 发生率11.9%, 平均发生时间25个月, 死亡2例。对照组静 脉曲张复发13例, 复发率43.3%, 平均复发时间18个月, 发生出血11例, 发生率36.7%, 平均发生时间18个月, 死亡7例。 治疗组在预防食管静脉曲张破裂出血, 降低病死率方面优于对照组。结论 结论 套扎术可作为预防晚血食管静脉曲张破裂出 血的方法。     

Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding

The aim of this study was to test the effectiveness of isosorbide-5-mononitrate (IM) as an adjunct to propranolol (PR) in the prevention of variceal rebleeding. Ninety-five cirrhotic patients with variceal bleeding were randomly assigned to treatment with PR + IM (46 patients) or PR alone (49 patients). Eighteen patients in the PR + IM group and 28 in the PR group had rebleeding during the 2 years after randomization. The actuarial probability of rebleeding 2 years after randomization was lower in the PR + IM group (40.4% vs. 57.4%) but the difference was not significant (P =. 09). However, the decrease in the risk of rebleeding reached statistical significance after stratification according to age, i.e. less than 50 versus >/=50 years old, (P =.03) or by adding an additional year of follow-up (P =.05). No significant difference was found in rebleeding index and survival. The multivariate Cox analysis indicated first, that both treatment (P =.03) and age (P =. 001) were factors predictive of rebleeding and second, that PR + MI reduced the risk of rebleeding by half (relative risk: 0.51, 95% confidence interval: 0.28-0.95). Seven patients in the PR + MI group and 1 patient in the PR group had to discontinue one of the drugs because of adverse events (P =.03). These results suggest that the addition of IM improves the efficacy of PR alone in the prevention of variceal rebleeding in cirrhotic patients. However no beneficial effects were observed on other parameters reflecting the efficacy of treatment.     

食管静脉曲张结扎术后早期再出血预测模型的建立

内窥镜下食管静脉曲张套扎术（EVL）是治疗肝硬化并发食管曲张静脉出血的有效手段，但存在术后再出血的可能，常危及生命。因此，有必要对EVL术后早期再出血的危险因素进行深入研究。我们通过对603例因食管曲张静脉破裂出血而单纯行EVL的肝硬化或伴原发性肝癌患者的资料进行回顾性分析，尝试建立一个预测EVL术后早期再出血的模型，以期有助于预后的判断和治疗方案的确立，从而减少再出血的发生。[第一段]     

Meta-analysis: beta-blockers versus banding ligation for primary prophylaxis of esophageal variceal bleeding

Aim. To perform an updated meta-analysis comparing β-blockers (BB) with endoscopic variceal banding ligation (EVBL) in the primary prophylaxis of esophageal variceal bleeding.Material and methods. Randomized controlled trials were identified through electronic databases, article reference lists and conference proceedings. Analysis was performed using both fixed-effect and random-effect models. Heterogeneity and publication bias were systematically taken into account. Main outcomes were variceal bleeding rates and all-cause mortality, calculated overall and at 6, 12, 18 and 24 months.Results. 19 randomized controlled trials were analyzed including a total of 1,483 patients. Overall bleeding rates were significantly lower for the EVBL group: odds ratio (OR) 2.06, 95% confidence interval (CI) [1.55-2.73], p < 0.0001, without evidence of publication bias. Bleeding rates were also significantly lower at 18 months (OR 2.20, 95% CI [1.04-4.60], P = 0.04), but publication bias was detected. When only high quality trials were taken into account, results for bleeding rates were no longer significant. No significant difference was found for either bleeding-related mortality or for all-cause mortality overall or at 6, 12, 18 or 24 months. BB were associated with more frequent severe adverse events (OR 2.61, 95% CI 1.60-4.40, P < 0.0001) whereas fatal adverse events were more frequent with EVBL (OR 0.14, 95% CI 0.02-0.99, P = 0.05).Conclusion. EVBL appears to be superior to BB in preventing the first variceal bleed, although this finding may be biased as it was not confirmed by high quality trials. No difference was found for mortality. Current evidence is insufficient to recommend EVBL over BB as first-line therapy.     

Endoscopic variceal ligation compared with endoscopic injection sclerotherapy for treatment of esophageal variceal hemorrhage:A meta-analysis

AIM:To compare the effect of endoscopic variceal ligation(EVL)with that of endoscopic injection sclerotherapy(EIS)in the treatment of patients withesophageal variceal bleeding.METHODS:We performed a systematic literature search of multiple online electronic databases.Metaanalysis was conducted to evaluate risk ratio(RR)and95%confidence interval(CI)of combined studies for the treatment of patients with esophageal variceal bleeding between EVL and EIS.RESULTS:Fourteen studies comprising 1236 patients were included in the meta-analysis.The rebleeding rate in actively bleeding varices patients in the EVL group was significantly lower than that in the EIS group(RR=0.68,95%CI:0.57-0.81).The variceal eradication rate in actively bleeding varices patients in the EVL group was significantly higher than that in the EIS group(RR=1.06,95%CI:1.01-1.12).There was no significant difference about mortality rate between the EVL group and EIS group(RR=0.95,95%CI:0.77-1.17).The rate of complications in actively bleeding varices patients in the EVL group was significantly lower than that in the EIS group(RR=0.28,95%CI:0.13-0.58).CONCLUSION:Our meta-analysis has found that EVL is better than EIS in terms of the lower rates of rebleeding,complications,and the higher rate of variceal eradication.Therefore,EVL is the first choice for esophageal variceal bleeding.     

Transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic variceal ligation in the prevention of variceal rebleeding in patients with cirrhosis: a randomised trial

BACKGROUND AND AIMS: The transjugular intrahepatic portosystemic shunt (TIPS) is a new therapeutic modality for variceal bleeding. In this study we compared the two year survival and rebleeding rates in cirrhotic patients treated by either variceal band ligation or TIPS for variceal bleeding. METHODS: Eighty cirrhotic patients (Pugh score 7-12) with variceal bleeding were randomly allocated to TIPS (n=41) or ligation (n=39), 24 hours after control of bleeding. RESULTS: Mean follow up was 581 days in the ligation group and 678 days in the TIPS group. The two year survival rate was 57% in the TIPS group and 56% in the ligation group (NS); the incidence of variceal rebleeding after two years was 18% in the TIPS group and 66% in the ligation group (p<0.001). Uncontrolled rebleeding occurred in 11 patients in the ligation group (eight were rescued by emergency TIPS) but in none of the TIPS group. The incidence of encephalopathy at two years was 47% in the TIPS group and 44% in the ligation group (NS). CONCLUSIONS: TIPS did not increase the two year survival rate compared with variceal band ligation after variceal bleeding in cirrhotic patients with moderate or severe liver failure. It significantly reduced the incidence of variceal rebleeding without increasing the rate of encephalopathy.     

Clinical algorithms for the prevention of variceal bleeding and rebleeding in patients with liver cirrhosis

Portal hypertension(PH), a common complication of liver cirrhosis, results in development of esophageal varices. When esophageal varices rupture, they cause significant upper gastrointestinal bleeding with mortality rates up to 20% despite state-of-the-art treatment. Thus, prophylactic measures are of utmost importance to improve outcomes of patients with PH. Several high-quality studies have demonstrated that non-selective beta blockers(NSBBs) or endoscopic band ligation(EBL) are effective for primary prophylaxis of variceal bleeding. In secondary prophylaxis, a combination of NSBB + EBL should be routinely used. Once esophageal varices develop and variceal bleeding occurs, standardized treatment algorithms should be followed to minimize bleeding-associated mortality. Special attention should be paid to avoidance of overtransfusion, early initiation of vasoconstrictive therapy, prophylactic antibiotics and early endoscopic therapy. Pre-emptive transjugular intrahepatic portosystemic shunt should be used in all Child C10-C13 patients experiencing variceal bleeding, and potentially in Child B patients with active bleeding at endoscopy. The use of carvedilol, safety of NSBBs in advanced cirrhosis(i.e. with refractory ascites) and assessment of hepatic venous pressure gradient response to NSBB is discussed. In the present review, we give an overview on the rationale behind the latest guidelines and summarize key papers that have led to significant advances in the field.     

内镜下食管静脉曲张套扎术治疗乙型肝炎肝硬化并发食管胃底静脉曲张破裂出血患者再出血风险观察*

目的 研究采用内镜下食管静脉曲张套扎术(EVL)治疗乙型肝炎肝硬化(LC)并发食管静脉曲张(EV)破裂出血患者治疗后再出血的风险。方法 2016年4月～2019年10月我科诊治的178例乙型肝炎肝硬化并发食管静脉曲张破裂出血(EVB)患者,在止血后采用EVL治疗,随访再出血发生情况,应用Cox风险回归模型进行多因素分析,建立Nomogram模型,预测再出血。结果 178例患者急性出血后,死亡12例(6.7%),166例接受EVL术,均获得成功;术后随访12～54个月,27例(16.3%)发生再出血;入院时,27例再出血组外周血Hb和血清白蛋白水平显著低于139例未再出血组(P<0.05),而空腹血糖(FPG)和糖化血红蛋白(HbA1c)水平显著高于未再出血组,差异均有统计学意义(P<0.05);入院止血后检查,发现再出血患者门静脉和脾静脉宽度显著大于未再出血组(P<0.05);Cox风险模型分析显示Child-Pugh分级(95%CI=1.125～3.439,HR=1.967,P=0.018)、腹水(95%CI=1.754～2.329,HR=2.021,P=0.000)、HbA1c(95%CI=1.173～1.921,HR=1.501,P=0.001)、FPG(95%CI=1.379～3.152,HR=2.085,P=0.000)和肝性糖尿病(95%CI=1.321～2.945,HR=2.076,P=0.006)是EVL术后再出血的独立影响因素;根据Cox建立Nomogram模型,ROC分析结果显示Nomogram判断术后再出血的AUC为0.804(SE=0.053,95%CI=0.700～0.907,P=0.000),其敏感度为0.857,特异度为0.565。结论 采取EVL治疗LC并发EVB患者术后再出血发生率较高,除常见的风险因素外,伴有肝性糖尿病也可能是重要的原因,临床应加强对血糖的控制,减少再出血的发生。