非选择性β受体阻滞剂预防静脉曲张出血及再出血

胃食管静脉曲张出血是肝硬化失代偿期常见的并发症，出血后1年内再出血率高达60%,门静脉压力升高是食管胃底静脉破裂出血的主要原因。非选择性β受体阻滞剂(NSBB)通过阻断β肾上腺素能受体降低门静脉压力，从而达到降低静脉曲张出血的风险，目前已成为胃食管静脉曲张出血一级和二级预防的首选药物，以HVPG指导的NSBB治疗和预防门静脉高压症患者首次和复发静脉曲张出血的个体化方案已引起临床关注，本文将结合最新的研究结果，探讨NSBB预防静脉曲张出血及再出血的个体化治疗。     

内镜治疗食管胃静脉曲张破裂出血的地位

食管胃底静脉曲张是肝硬化门脉高压患者常见的临床表现之一,破裂出血是其主要危害和致死性并发症。近年来随着血管活性药物、内镜、介入技术等技术的进步,病死率较前下降。内镜检查与治疗在食管胃底静脉曲张患者的多学科治疗和个体化处理过程中均有不可替代的重要地位。现从食管胃底静脉曲张的筛查、预防初次出血、急诊止血、预防再出血等方面回顾近年来国内外的研究进展,阐述并评价内镜治疗在食管胃静脉曲张破裂出血方面的地位与存在的争议问题。     

介入治疗

控制食管胃底静脉曲张破裂出血并防止再出血,是门静脉高压治疗的重点.随着影像技术的发展和介入材料的改进,介入疗法已成为该病治疗的重要措施之一.     

肝硬化食管胃静脉曲张破裂出血的临床处理动向

治疗肝硬化食管胃静脉曲张破裂出血的首选措施是药物治疗,可选用特利加压素、生长抑素类似物等;硝酸酯类药物、分流术或硬化疗法均不建议用于一级预防;非选择性β受体阻滞剂联合内镜下曲张静脉套扎术是目前二级预防中的首选措施。     

门静脉高压并食管胃底静脉曲张出血的治疗策略

食管胃底静脉曲张破裂出血是门静脉高压的严重并发症,如何控制食管胃底静脉曲张破裂出血并预防再出血,是救治肝硬化患者生命的关键。简述了门静脉高压食管胃底静脉曲张出血的治疗和预防的4个阶段,指出应根据患者不同的临床时期、不同的肝静脉压力梯度、不同的肝功能分级,选择不同的治疗策略。     

食管胃底静脉曲张破裂出血预防和治疗进展*

目的 食管胃底静脉曲张破裂出血是肝硬化常见的并发症, 病死率高。因此,预防和治疗食管胃底静脉曲张破裂出血对于肝硬化患者非常重要。药物治疗、内镜治疗、介入治疗和外科手术治疗等都是预防和治疗该病的重要手段,各有疗效,极大地提高了患者生存率。本文针对不同食管胃底静脉曲张类型的一级预防、急症止血和二级预防治疗现状及研究进展作一综述。     

食管胃底静脉曲张首次出血的药物预防

食管胃底静脉曲张是肝硬化的严重并发症,大约有40%的静脉曲张病人发生自发破裂出血,尽管目前治疗手段在不断的改善,但出血后6周内的总病死率仍高达20%。食管胃底静脉曲张破裂出血是肝硬化最严重的致死性并发症,本文就目前预防食管胃底静脉曲张首次出血的药物治疗措施做一综述。     

内镜套扎加硬化治疗对食管胃底静脉曲张的疗效

食管胃底静脉曲张破裂出血是肝硬化门静脉高压症的严重并发症,由于多数患者伴有严重肝功能损害,死亡率和再出血率高。近年来,人们已找到许多方法有效地预防和治疗急性静脉曲张破裂出血,内镜多环套扎术(EndoscopicMultiple Ligation,EML)和内镜下食管静脉曲张硬化术(En-doseopic Variceal Sclerotheraphy,EVS)便是其中两种。1997年9月以来,我们采用EML加EVS治疗食管胃底静脉曲张,并尝试对无出血史者行预防性治疗,取得较好效果。     

重视食管胃底静脉曲张的治疗北大核心CSCD

食管胃底静脉曲张与食管胃底静脉曲张破裂出血(esophageal-gastric variceal bleeding,EGVB)关系密切,后者是消化科中较为常见且极为凶险的肝硬化并发症,正确且有效地治疗与预防食管胃底静脉曲张尤为重要,其中最主要的手段即合理运用各类相关治疗方式包括药物、内镜、介入等,不断发展的技术对医师及医疗机构提出了更高的要求,不断学习、认识食管胃底静脉曲张,才能更加有效地针对其各类表现早期辨别、预防、治疗。     

门静脉高压症的外科治疗——介入治疗

控制食管胃底静脉曲张破裂出血并防止再出血，是门静脉高压治疗的重点。随着影像技术的发展和介入材料的改进，介入疗法已成为该病治疗的重要措施之一。     

Update on treatment of variceal hemorrhage

Variceal hemorrhage accounts for one third of all deaths related to cirrhosis. To date, many modalities of treating variceal bleeding have been devised, including pharmacological therapy. Treatment of variceal hemorrhage includes resuscitation, initial hemostasis, and prevention of complications and recurrent bleeding. Intravenous vasoactive agents such as terlipressin, somatostatin, octreotide, or vapreotide should be administered in patients with suspected variceal bleeding. Endoscopic treatment remains the mainstay of treatment. Endoscopic variceal ligation is safer and more efficacious than sclerotherapy as initial treatment of bleeding esophageal varices, whereas cyanoacrylate injection is the endoscopic treatment of choice for gastric varices. An adjuvant vasoactive agent is useful for the prevention of early rebleeding. Prophylactic antibiotics are increasingly used for prevention of infection, notably spontaneous bacterial peritonitis. Follow-up endoscopic treatment is necessary in order to obliterate residual varices. The combination of a beta blocker and nitrate is an essential component of secondary prophylaxis for recurrent variceal bleeding. Transjugular intrahepatic portosystemic shunt or surgery offers the best salvage therapy in patients with failed hemostasis or breakthrough recurrent bleeding despite medical and endoscopic therapy. Endoscopic ultrasonography is useful in the prediction of recurrence of varices and facilitates visualization and guidance of further treatment of gastric varices. Despite advances in the treatment of variceal bleeding, liver function remains the determining factor of patient survival. Liver transplantation is the only definitive treatment that can alter the course of the disease.     

Variceal Bleeding

Opinion statement Primary prophylaxis: Patients with cirrhosis who have esophageal varices but who have never had a bleeding episode may be treated medically or endoscopically. Without treatment, approximately 30% of cirrhotic patients with varices bleed and this risk is reduced by approximately 50% with therapy. Medical therapy includes nonselective beta blockers with or without nitrates. Compliance and side effects limit efficacy. Primary prophylaxis with endoscopic sclerotherapy is not warranted because of evidence suggesting that complications outweigh benefits. Studies of endoscopic therapy with ligation (endoscopic banding) demonstrate that in select patients (those with large varices), endoscopic banding may reduce the risk of first bleeding episode when compared with propranolol. Patients with large varices may benefit from a combination of banding with nonselective beta blockers. Secondary prophylaxis: After an initial variceal bleed, the risk of a second bleed is high and therapy is warranted to reduce the risk of rebleeding. The options are similar to those for primary prophylaxis, and in addition to medical and endoscopic therapy, transjugular intrahepatic portosystemic shunts (TIPS) and surgical shunts are therapeutic options. The combination of endoscopic therapy with medical therapy is the initial approach to prevent variceal rebleeding. Endoscopic banding is preferred to sclerotherapy because banding is associated with lower bleeding rates and fewer complications. TIPS is useful in cases refractory to endoscopic therapy or in uncontrolled variceal hemorrhage. Surgical shunts are typically reserved for patients in whom TIPS cannot be performed for technical reasons or for well-compensated cirrhotic patients. Acute variceal bleeding: Acute bleeding from esophageal varices requires an endoscopic evaluation and therapeutic intervention. Technically, endoscopic banding may not be possible because of limited visualization from bleeding and sclerotherapy is used because it is easier to perform in this setting. A continuous intravenous drip of octreotide should be initiated if variceal bleeding is suspected. If variceal bleeding cannot be controlled, then a Minnesota tube or Sengstaken-Blakemore tube should be placed by someone with experience. TIPS is effective rescue therapy for controlling acute variceal hemorrhage in circumstances when other methods fail.     

Nonsurgical treatment of variceal bleeding

Opinion statement Patients with cirrhosis, especially those who have a platelet count of less than 100,000, who are considered compliant, and have no contraindications to beta-blocker therapy, should have a screening endoscopy to ascertain the presence of esophageal varices. Patients with medium to large esophageal varices who are appropriate candidates should be placed on a nonselective beta-blocker (propranolol hyrdochloride, nadolol, timolol maleate) for the prevention of initial variceal hemorrhage. Patients presenting with acute variceal hemorrhage, as determined endoscopically, should be treated with a combination of vasoactive drugs and endoscopic therapy (sclerotherapy or variceal ligation) for the control of acute variceal bleeding and the prevention of early rebleeding. Transjugular intrahepatic portosystemic shunt (TIPS) should be reserved for failures of initial medical therapy. After successful control of initial variceal bleeding is reached, the rebleeding rate approaches 70% in most studies, with the highest risk period being in the first 6 months after control of the index bleed is obtained [1]. Therefore, all patients should be placed on therapy to prevent recurrent variceal bleeding. Options include pharmacologic therapy, endoscopic therapy, and combinations of endoscopic and pharmacologic therapy. TIPS, surgical shunts, and liver transplantation should be reserved for special circumstances and in general, should only be considered for failures of initial medical therapy.     

非选择性β受体拮抗剂在肝硬化门静脉高压患者中的合理应用

曲张静脉出血是肝硬化门静脉高压患者最常见和最严重的并发症之一。近三十余年来,尽管对其治疗取得了进展,但其相关病死率仍达15%～20%左右。不仅如此,曲张静脉出血常导致肝功能进一步的恶化,也是诱发肝硬化其他并发症的共同启动因素。因此,预防曲张静脉首次出血与再出血是提高失代偿期肝硬化和食管曲张静脉患者生存率的重要措施。非选择性β受体阻滞剂（nonselective beta-blockers,NSBB）因具有明确地降低肝静脉压力剃度的作用,被推荐用于预防曲张静脉首次出血和再出血。尽管该类药物具有耐受性好、口服方便和经济实惠的优点,但在使用过程中因存在副作用和潜在的不良作用,一般推荐应有选择地用于那些高危的曲张静脉患者。     

特利加压素联合内镜静脉曲张套扎术预防急性食管静脉曲张破裂再出血的研究

背景：食管胃底静脉曲张破裂出血是肝硬化的危重并发症之一,内镜静脉曲张套扎术（EVL）是食管静脉曲张破裂出血的首选内镜治疗方案。对于急性食管静脉曲张破裂出血患者,推荐于EVL术后使用血管活性药物特利加压素3—5d以预防早期再出血。目的：明确特利加压素联合EVL对急性食管静脉曲张破裂再出血的预防作用。方法：96例急诊食管静脉曲张破裂出血患者行EVL后随机分为2组,对照组口服普萘洛尔10mg／d×5d,干预组静脉推注特利加压素1mg／d×5d,其后两组患者均以维持剂量长期服用普萘洛尔。记录术后5d内和3个月内的再出血发生情况。结果：干预组早期（5d内）再出血率显著低于对照组（2．1％对12．5％,P〈0．05）,两组近期（3个月内）再出血率无明显差异（4．2％对14．6％,P〉0．05）。结论：急诊EVL联合特利加压素预防急性食管静脉曲张破裂早期再出血的效果优于EVL联合普萘洛尔,远期结果尚需进一步随访观察。     

Combination Endoscopic Band Ligation and Sclerotherapy Compared with Endoscopic Band Ligation Alone for the Secondary Prophylaxis of Esophageal Variceal Hemorrhage: A Meta-Analysis

Endoscopic band ligation (EBL) is the community-accepted standard therapy for the secondary prophylaxis of esophageal variceal hemorrhage. Recent data indicate that combination EBL and sclerotherapy may be a more effective therapy than EBL alone. Yet existing data are conflicting. We therefore performed a meta-analysis to compare the efficacy and safety of EBL and sclerotherapy versus EBL alone for the secondary prophylaxis of esophageal variceal hemorrhage. We performed a systematic review of two computerized databases (MEDLINE and EMBASE) along with manual-searching of published abstracts to identify relevant citations without language restrictions from 1990 to 2002. Eight studies met explicit inclusion criteria. We performed meta-analysis of these studies to pool the relative risk for the following outcomes: esophageal variceal rebleeding, death, number of endoscopic sessions to achieve variceal obliteration, and therapeutic complications. There were no significant differences between EBL and sclerotherapy versus EBL alone in the risk of esophageal variceal rebleeding (RR = 1.05; 95% CI = 0.67–1.64; P = 0.83), death (RR = 0.99; 95% CI = 0.68–1.44; P = 0.96), or number of endoscopic sessions to variceal obliteration (RR = 0.23; 95% CI = 0.055–0.51; P = 0.11). However, the incidence of esophageal stricture formation was significantly higher in the EBL group than in the sclerotherapy group. There is no evidence that the addition of sclerotherapy to endoscopic band ligation changes clinically relevant outcomes (variceal rebleeding, death, time to variceal obliteration) in the secondary prophylaxis of esophageal variceal hemorrhage. Moreover, combination EBL and sclerotherapy had more esophageal stricture formation than EBL alone.     

Pharmacologic therapy for gastrointestinal bleeding due to portal hypertension and esophageal varices

Cirrhosis results in portal hypertension in many patients. The major complications of portal hypertension include development of ascites and esophageal or gastric varices. Varices lead to hemorrhage and death in a significant proportion of patients. This review focuses on the pharmacologic approach to management of portal hypertension in patients at risk of variceal hemorrhage, or those who have already had variceal bleeding. Pharmacologic therapy is used for 1) primary prevention of bleeding, 2) management of acute bleeding, and 3) prevention of recurrent bleeding (secondary prophylaxis). For acute esophageal variceal hemorrhage, a variety of pharmacologic agents are used, including somatostatin, octreotide, vapreotide, lanreotide, terlipressin, and vasopressin (with nitrates). For primary and secondary prevention of esophageal variceal hemorrhage, a-blockers remain the mainstay therapy.     

Portal hypertensive bleeding

Portal hypertension bleeding is a common and serious complication of cirrhosis. All patients with cirrhosis should undergo endoscopy and be evaluated for possible causes of current or future portal hypertensive bleeding. Possible causes of bleeding include esophageal varices, gastric varices, and PHG. Patients with esophageal varices at high risk of bleeding should be treated with nonselective beta-blockers for primary prevention of variceal hemorrhage. HVPG measurements represent the optimal way to monitor the success of pharmacologic therapy. EVL may be used in those with high-risk varices who do not tolerate beta-blockers. When active bleeding develops, simultaneous and coordinated attention must be given to hemodynamic resuscitation, prevention and treatment of complications, and active control of bleeding. In cases of acute esophageal variceal (Fig. 5) and PHG bleeding, terlipressin, somatostatin, or octreotide should be started. Endoscopic treatment is provided for those with bleeding esophageal varices. If first-line therapy fails, TIPS or surgery may need to be performed. Unlike esophageal variceal or PHG bleeding, there is no established optimal treatment for gastric variceal bleeding. Individual and specific treatment modalities for acute gastric variceal bleeding must be calculated carefully after considering side effects.     

Portale Hypertension: Varizen

Background

Variceal hemorrhage is a major cause of morbidity and mortality in patients with cirrhosis. However, mortality rates have been substantially reduced in recent years due to improved diagnostic and therapeutic workup.

Therapy

Patients who present with active variceal hemorrhage require immediate hemodynamic resuscitation and early upper gastrointestinal endoscopy. Endoscopic variceal ligation (EVL) is the treatment of choice for esophageal varices, whereas cyanoacrylate injection is preferably used for the treatment of gastric varices. If endoscopic therapy fails to control bleeding, balloon tamponade or stent placement may be required. Emergency transjugular intrahepatic portosystemic shunt (TIPS) placement is a more definite option, when available.

Prophylaxis

For primary prophylaxis of variceal hemorrhage, treatment with a nonselective beta blocker or EVL is recommended whereas a combination of the two is recommended for secondary prophylaxis.

     

经皮经肝曲张静脉栓塞治疗断流术后食管胃底静脉破裂出血的疗效

目的 研究以组织胶为主要栓塞材料,采用经皮经肝曲张静脉栓塞术(PTVE)治疗和预防门奇静脉断流术后食管胃底静脉曲张破裂出血的临床疗效.方法 2006年11月至2008年9月,对22例曾行断流术再发食管胃底静脉曲张破裂出血的患者行PTVE组织胶栓塞(n=10)或内镜下硬化剂(EIS,n=12)治疗,随访两组患者治疗后再出血率、死亡率、治疗前后静脉曲张和肝功能以及PTVE治疗组患者在曲张侧支静脉栓塞前后门静脉压力的变化.结果 ①在平均12.5个月的随访期内,PTVE治疗组患者再出血率和死亡率分别为1/10和0;EIS治疗组随访13.4个月,患者再出血率和死亡率分别为7/12和3/12,两组问差异有统计学意义(P<0.05).②PTVE和EIS治疗均可显著减轻食管和胃底静脉曲张程度.③对有门静脉血栓患者,PTVE联合门静脉球囊成形术,可以改善肝脏门静脉血供.④PTVE和EIS治疗均未加重肝功能损伤.结论 对门奇静脉断流术后食管胃底静脉破裂出血的患者,采用以组织胶为主要栓塞材料的PTVE治疗的疗效优于EIS治疗.