The role of endoscopy in portal hypertension

Endoscopy plays a major role in the management of gastrointestinal varices in portal hypertension. It is used for the prophylaxis of the first bleeding episode, therapy of active bleeding and prophylaxis of recurrent bleeding. Today not only nonselective betablockers, but also endoscopic band ligation is an option in the primary prophylaxis of the first bleeding episode in patients with large esophageal varices. Acutely bleeding varices should be treated by ligation, pharmacological and antibiotic therapy. Prophylaxis of recurrent bleeding despite endoscopic and pharmacologic treatment is patient dependent: shunt surgery is an option in young patients in a good medical condition (Child-Pugh class A). In patients with refractory ascites and a bilirubin level below 3 mg/dl, TIPS is a good option. Nevertheless, the first-line treatment in most patients in Germany is endoscopic band ligation. Bleeding from ectopic varices and due to hypertensive gastropathy should be treated individually either by endoscopy, TIPS or drug therapy.     

Portal hypertension and gastrointestinal bleeding:Diagnosis,prevention and management

Bleeding from esophageal varices is a life threatening complication of portal hypertension.Primary prevention of bleeding in patients at risk for a first bleeding episode is therefore a major goal.Medical prophylaxis consists of non-selective beta-blockers like propranolol or carvedilol.Variceal endoscopic band ligation is equally effective but procedure related morbidity is a drawback of the method.Therapy of acute bleeding is based on three strategies:vasopressor drugs like terlipressin,antibiotics and endoscopic therapy.In refractory bleeding,self-expandable stents offer an option for bridging to definite treatments like transjugular intrahepatic portosystemic shunt(TIPS).Treatment of bleeding from gastric varices depends on vasopressor drugs and on injection of varices with cyanoacrylate.Strategies for primary or secondary prevention are based on non-selective beta-blockers but data from large clinical trials is lacking.Therapy of refractory bleeding relies on shuntprocedures like TIPS.Bleeding from ectopic varices,portal hypertensive gastropathy and gastric antral vascular ectasia-syndrome is less common.Possible medical and endoscopic treatment options are discussed.     

Diagnosis and treatment of portal hypertension

Prevention of the first variceal haemorrhage should start when the patients have developed medium-sized to large varices. Non-selective beta-blockers and band ligation are equally effective in preventing the first bleeding episode. Rubber band ligation is the first choice for patients with contraindications or intolerance to beta-blockers.

Treatment of acute bleeding should aim at controlling bleeding and preventing early rebleeding and complications, especially infections. Combined endoscopic (band ligation or sclerotherapy) and pharmacological treatment with vasoactive drugs can control bleeding in up to 90% of patients. Antibiotic prophylaxis is an integral part of the treatment of acute variceal haemorrhage, and must be started as soon as possible. Emergency transjugular intrahepatic portosystemic stent shunt (TIPS) is the standard rescue therapy for patients failing combined endoscopic and pharmacological treatment.

All patients who survive a variceal bleed should be treated with beta-blockers or band ligation to prevent rebleeding. All patients in whom bleeding cannot be controlled or who continue to rebleed can be treated with salvage TIPS or, in selected cases, with surgical shunts. Liver transplantation should be considered for patients with severe liver insufficiency in which first-line treatments fail.     

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.     

Current management of esophageal varices

Opinion statement Acute variceal hemorrhage is the most lethal complication of cirrhosis. The reported mortality rate from a first episode of variceal hemorrhage is 17% to 57%. Management of varices can be categorized into three phases: 1) prevention of initial bleeding, 2) management of acute bleeding, and 3) prevention of rebleeding. Modalities for treatment include pharmacologic, endoscopic, and shunt therapy. For the prevention of first variceal hemorrhage, cirrhotic patients should undergo endoscopy to identify patients with large varices. Priority for screening for varices should be given to patients with low platelet count, splenomegaly, and advanced cirrhosis. Once large varices are identified, patients should be started on β-blocker therapy, which reduces the risk of bleeding by 50%. If pharmacologic therapy is not tolerated or contraindicated, endoscopic band ligation should be performed, and surveillance of varices should be performed every 6 months thereafter. Shunt procedures are not indicated due to their higher rates of complications compared with medical therapy. For the management of acute variceal hemorrhage, patients should be started on prophylactic intravenous antibiotics and intravenous octreotide. Endoscopy should be performed to diagnose and treat variceal hemorrhage. Band ligation appears to be as effective as sclerotherapy, but with less complications. If hemostasis is not achieved, balloon tamponade can be used as a bridge to definitive therapy, which in this case would be a transjugular intrahepatic portosystemic shunt (TIPS). If TIPS is unavailable, a surgical shunt is indicated. Once an episode of acute bleeding has been controlled, variceal eradication is best accomplished with repeat band ligation every 10 to 14 days until varices are obliterated. Prevention of recurrent bleeding can be achieved with β-blocker therapy. The addition of isosorbide mononitrate further reduces recurrent bleeding. This combination pharmacologic therapy has been shown to be superior to sclerotherapy and may be superior to band ligation. However, side effects of combination pharmacologic therapy may limit its effectiveness. Band ligation is preferred to sclerotherapy when considering endoscopic therapy due to less complications and lower cost. Surgical shunts should be used for prevention of rebleeding in patients who do not tolerate or are noncompliant with medical therapy and who have relatively preserved liver function. TIPS should be reserved for patients who have poor liver function and who have failed medical therapy.     

Endoscopic treatment of esophageal varices in patients with liver cirrhosis

Variceal bleeding is a life-threatening complication of portal hypertension with a six-week mortality rate of approximately 20%. Patients with medium- or large-sized varices can be treated for primary prophylaxis of variceal bleeding using two strategies: non-selective beta-blockers(NSBBs) or endoscopic variceal ligation(EVL). Both treatments are equally effective. Patients with acute variceal bleeding are critically ill patients. The available data suggest that vasoactive drugs, com-bined with endoscopic therapy and antibiotics, are the best treatment strategy with EVL being the endoscopic procedure of choice. In cases of uncontrolled bleeding, transjugular intrahepatic portosystemic shunt(TIPS) with polytetrafluoroethylene(PTFE)-covered stents are recommended. Approximately 60% of the patients experience rebleeding, with a mortality rate of 30%. Secondary prophylaxis should start on day six following the initial bleeding episode. The combination of NSBBs and EVL is the recommended management, whereas TIPS with PTFE-covered stents are the preferred op-tion in patients who fail endoscopic and pharmacologic treatment. Apart from injection sclerotherapy and EVL, other endoscopic procedures, including tissue adhe-sives, endoloops, endoscopic clipping and argon plasmacoagulation, have been used in the management of esophageal varices. However, their efficacy and safety, compared to standard endoscopic treatment, remain to be further elucidated. There are safety issues accompa-nying endoscopic techniques with aspiration pneumonia occurring at a rate of approximately 2.5%. In conclu-sion, future research is needed to improve treatment strategies, including novel endoscopic techniques with better efficacy, lower cost, and fewer adverse events.     

Prevention of recurrent haemorrhage

Patients who survive a first bleeding episode of oesophageal varices have a high risk of rebleeding, which is associated with a high mortality rate. Prevention of a recurrent haemorrhage is therefore recommended. Patients who were not on a primary prophylaxis should be treated with non-selective beta-adrenoceptor antagonists, endoscopic band ligation or both. If beta-blockers are not tolerated or are contraindicated, patients should be treated with endoscopic band ligation. If these preventive strategies fail, transjugular intrahepatic portosystemic shunt (covered) or a small-diameter surgical shunt is indicated.     

Endoscopic management of variceal bleeding

For the primary prophilaxis of the variceal bleeding, non selective beta-blockers (propanolol, nadolol) are still the mainstay of treatment but endoscopic ligation are becoming more popular Thanks to modern control procedures the acute bleeding mortality has been reduced. Endoscopic ligation is the prefered method for esophageal varices and the cyanoacrylate injection is the better method for fundic varices. Pharmacological therapy with octreotide or terlipresine seems to be effective, specially if endoscopic treatment is not available. TIPS is a good salvage option in case of endoscopic or pharmacologic failure. Endoscopic ligation seems to be the prefered method for secondary prophylaxis, specially compared with sclerotherapy. Some drugs that reduce portal hypertension are a good alternative. It is still very necessary to define technique and criteria of endoscopic variceal eradication to reduce the great variability reported in published trials.     

Portal hypertension. Evidence-based guide

Treatment of portal hypertension has evolved widely during the last decades. Advances in physiopathology have allowed better application of therapeutic options and also have permitted to know the natural history of varices and variceal bleeding, predicting which patients have a higher risk of bleeding. It also permits probability of designing patient treatment. According to liver function and subadjacent liver disease, it is possible to offer different alternatives within the three possible scenarios (primary prophylaxis, acute bleeding episode, and secondary prophylaxis). For primary prophylaxis, pharmacotherapy offers the best choice. Endoscopic banding is also growing in these scenarios and probably will be accepted in the near future. For the acute bleeding episode, endoscopic therapy (sclerosis and/or bands) and/or pharmacologic therapy (octreotide, terlipresin) represent best choice, considering TIPS as a rescue option. Surgery is not used routinely in this scenario in most centers. For secondary prophylaxis, pharmaco- and endoscopic therapy are first-line treatments, while TIPS and surgery as second-line treatments. TIPS is mainly used in patients on a waiting list for liver transplantation. Surgery offers good results for low-risk patients, with good liver function and with portal blood-flow preserving procedures (selective shunts, extensive devascularizations). Liver transplantation is recommended for patients with poor liver function because together with portal hypertension, it treats subadjacent liver disease.     

Portale Hypertension

Bleeding of gastro-oesophageal varices is one of the most serious complications of portal hypertension. An early endoscopic examination of patients with cirrhosis has become standard practice because direct measurement of portal pressure is not universally available. If varices are present prophylaxis to prevent bleeding can be achieved by non-selective betablocker therapy. In the face of contraindications or intolerance to this therapy, endoscopic band ligation is an alternative prevention strategy for high-risk patients. Acute variceal haemorrhaging can be controlled in about 90% of the cases by endoscopic sclerotherapy or band ligation. In addition, vasoactive drugs like octreotide or terlipressin can be used to reduce portal pressure and to control haemorrhaging. Prevention of recurrent bleeding can be achieved through a consistent band ligation. The most promising therapy for gastric variceal bleeding is the injection of histoacryl. In cases of endoscopic treatment failure, a balloon tamponade or a portosystemic shunt are rescue treatment options.     

A cost-effectiveness study of hepatic venous pressure gradient measurement in the secondary prevention of variceal bleeding

OBJECTIVE: variceal rebleeding is common following a first episode of hemorrhage in cirrhotic patients. The objective of this study was to determine the cost-effectiveness of monitoring hepatic venous pressure gradient (HVPG) to guide secondary prophylaxis. METHODS: we created a Markov decision model to calculate cost-effectiveness for two strategies: Group 1: HVPG monitoring to decide treatment -when portal pressure was reduced by at least 20 percent or HVPG was less than 12 mmHg after beta-blocker administration, patients received beta-blockers; when portal pressure did not meet these criteria therapy was endoscopic band ligation. Group 2: in this group there was no monitoring of HVPG. Patients with large varices received treatment with beta-blockers combined with EBL; patients with small varices received beta-blockers plus isosorbide mononitrate. RESULTS: there was no recurrent variceal bleeding in group 1 for good responders, and for 17% of poor responders. In group 2 a 25% rebleeding rate was detected in patients with small varices and 13% for those with big varices. Overall cost in group 1 was 14,100.49 euros, and 14,677.16 in group 2. CONCLUSIONS: HVPG measurement is cost-effective for the secondary prophylaxis of variceal bleeding.     

Management of upper gastrointestinal haemorrhage

Abstract Endoscopic therapy is the first treatment modality in the management algorithm of upper gastrointestinal haemorrhage. In treating bleeding peptic ulcers, diluted epinephrine is first injected followed by targeted treatment to the vessel. Combination therapy adding thermocoagulation or thrombin/fibrin products has been shown to further improve the rate of haemostasis. There is also some evidence to suggest that adjuvant use of optimal acid suppression using high-dose proton pump inhibitors can reduce recurrent bleeding after initial endoscopic control. In treating acute variceal haemorrhage, early administration of vasoactive agents facilitates endoscopic treatment. These drugs should be continued during and after endoscopic therapy to prevent recurrent in-hospital bleeding. Firm evidence exists to date that band ligation is the endoscopic treatment of choice in the acute control of bleeding varices and their secondary prophylaxis against recurrent bleeding. The role of band ligation as primary prophylaxis for first bleeding remains controversial. Transjugular intrahepatic porto-systemic shunts are used as a rescue procedure when endoscopic treatment fails. In selected patients with recurrent variceal haemorrhage and good hepatic reserves, surgical shunts may be indicated.     

Treatment of portal hypertension

Portal hypertension is the main complication of cirrhosis and is defined as an hepatic venous pressure gradient (HVPG) of more than 5 mmHg. Clinically significant portal hypertension is defined as HVPG of 10 mmHg or more. Development of gastroesophageal varices and variceal hemorrhage are the most direct consequence of portal hypertension. Over the last decades significant advancements in the field have led to standard treatment options. These clinical recommendations have evolved mostly as a result of randomized controlled trials and consensus conferences among experts where existing evidence has been reviewed and future goals for research and practice guidelines have been proposed. Management of varices/variceal hemorrhage is based on the clinical stage of portal hypertension. No specific treatment has shown to prevent the formation of varices. Prevention of first variceal hemorrhage depends on the size/characteristics of varices. In patients with small varices and high risk of bleeding, non-selective β-blockers are recommended, while patients with medium/large varices can be treated with either β-blockers or esophageal band ligation. Standard of care for acute variceal hemorrhage consists of vasoactive drugs, endoscopic band ligation and antibiotics prophylaxis. Transjugular intrahepatic portosystemic shunt (TIPS) is reserved for those who fail standard of care or for patients who are likely to fail ("early TIPS"). Prevention of recurrent variceal hemorrhage consists of the combination of β-blockers and endoscopic band ligation.     

Variceal bleeding and portal hypertensive gastropathy

Cirrhosis can be the end stage of any chronic liver disease. At the time of diagnosis of cirrhosis varices are present in about 60% of decompensated and 30% of compensated patients. The risk factors for the first episode of variceal bleeding in cirrhotic patients are the severity of liver dysfunction, large size of varices and the presence of endoscopic red colour signs but only one-third of patients who have variceal haemorrhage have the above risk factors. Recent interest has been directed at identifying haemodynamic factors that may reflect the pathophysiological changes which lead to variceal bleeding, e.g. it has been confirmed that no bleeding occurs if HVPG falls below 12 mmHg and also a hypothesis has been put forward in which bacterial infection is considered a trigger for bleeding. Pharmacological treatment with beta-blockers is safe, effective and is the standard long-term treatment for the prevention of recurrence of variceal bleeding. Combination of beta-blockers with isosorbide-5-mononitrate needs further testing in randomized controlled trials. The use of haemodynamic targets for reduction in HVPG response needs further study, and surrogate markers of pressure response need evaluation. If endoscopic treatment is chosen, variceal ligation is the modality of choice. The combination of simultaneous variceal ligation and sclerotherapy does not offer any benefit. However, the use of additional sclerotherapy for the complete eradication of small varices after variceal ligation needs to be evaluated. The results of current prospective randomized controlled trials comparing variceal ligation with pharmacological treatment are awaited with great interest. Finally, the use of transjugular intrahepatic portosystemic shunt (TIPS) for the secondary prevention of variceal bleeding is not substantiated by current data, as survival is not improved and because of its worse cost-benefit profile compared to other treatments. In contrast, there still is a role for the selective surgical shunts in the modern management of portal hypertension. The ideal patients should be well compensated cirrhotics, who have had troublesome bleeding - either who have failed at least one other modality of therapy (drugs or ligation), have bled from gastric varices despite medical or endoscopic therapy, or live far from suitable medical services. Recently, ligation has been compared to beta-blockers for primary prophylaxis but so far there is no good evidence to recommend banding for primary prophylaxis, if beta-blockers can be given.     

Bleeding caused by portal hypertension

Variceal bleeding is one of the dreaded complications of portal hypertension. Patients who have suspected or proven cirrhosis should undergo diagnostic upper endoscopy to detect medium and large gastro-esophageal varices. Patients with medium and large gastro-esophageal varices should be treated with non-selective beta-blockers (propranolol or nadolol), and these agents should be titrated to a heart rate of 55 beats per minute or adverse effects. If there are contraindications to or if patients are intolerant to beta-blockers, it is appropriate to consider prophylactic banding therapy for individuals with medium-to-large esophageal varices. When patients who have cirrhosis present with GI bleeding, they should be resuscitated and receive octreotide or other vasoactive agents. Endoscopy should be performed promptly to diagnose the source of bleeding and to provide endoscopic therapy (preferably banding). The currently available treatment for acute variceal bleeding provides hemostasis in most patients. These patients, however, are at significant risk for rebleeding unless secondary prophylaxis is provided. Although various pharmacological, endoscopic, radiological, and surgical options are available, combined pharmacological and endoscopic therapy is the most common form of secondary prophylaxis. TIPS is a radiologically placed portasystemic shunt, and if placed in suitable patients, it can provide effective treatment for patients with variceal bleeding that is refractory to medical and endoscopic therapy.     

Medical treatment of portal hypertension

Prevention of the first variceal haemorrhage should start when the patients have developed medium sized to large varices. Non-selective beta-blockers are the first-line treatment; band ligation is roughly equivalent to beta-blockers and is the first choice for patients with contraindications or intolerance to beta-blockers. Treatment of acute bleeding should aim at controlling bleeding and preventing early rebleeding and complications, especially infections. Combined endoscopic and pharmacological treatment with vasoactive drugs can control bleeding in up to 90% of patients. All patients who survive a variceal bleed should be treated with beta-blockers or band ligation to prevent rebleeding. All patients in whom bleeding cannot be controlled or who continue to rebleed can be treated with salvage TIPS or, in selected cases, with surgical shunts. Liver transplantation should be considered for patients with severe liver insufficiency in which first-line treatments fail.     

Motion - prophylactic banding of esophageal varices is useful: arguments for the motion.

Variceal hemorrhage is a frequent complication of cirrhosis and is associated with a high mortality rate, especially in patients with decompensated liver disease. Endoscopy is useful in identifying factors that predict a high likelihood of bleeding, including large varices and red colour signs. Endoscopic rubber band ligation has superseded sclerotherapy in the prevention of both recurrent hemorrhage and the first episode of bleeding, because it causes fewer complications and requires fewer sessions to eradicate varices. It has been proven to be more effective than nontreatment in the primary prophylaxis against variceal hemorrhage. There is extensive literature that has found that band ligation is more effective than beta-adrenergic receptor antagonists at preventing the first variceal hemorrhage. There is ongoing debate about the relative merits of these two approaches, but the available evidence supports the conclusion that band ligation is the treatment of choice in the primary prevention of variceal bleeding. Trials of combined medical and endoscopic therapy are eagerly awaited, and the author suspects that it may prove to be more effective than either modality alone.     

Endoscopic band ligation in the treatment of portal hypertension

The evidence that endoscopic band ligation (EBL) has greater efficacy and fewer side effects than endoscopic injection sclerotherapy has renewed interest in endoscopic treatments for portal hypertension. The introduction of multishot band devices, which allow the placement of 5-10 bands at a time, has made the technique much easier to perform, avoiding the use of overtubes and their related complications. EBL sessions are usually repeated at 2 week intervals until varices are obliterated, which is achieved in about 90% of patients after 2-4 sessions. Variceal recurrence is frequent, with 20-75% of patients requiring repeated EBL sessions. According to current evidence, nonselective beta-blockers are the preferred treatment option for prevention of a first variceal bleed, whereas EBL should be reserved for patients with contraindications or intolerance to beta-blockers. Nonselective beta-blockers, probably in association with the vasodilator isosorbide mononitrate, and EBL are good treatment options to prevent recurrent variceal rebleeding. The efficacy of EBL might be increased by combining it with beta-blocker therapy. Patients who are intolerant, have contraindications or bled while receiving primary prophylaxis with beta-blockers must be treated with EBL. In the latter situation, EBL should be added to rather than replace beta-blocker therapy. EBL, in combination with vasoactive drugs, is the recommended form of therapy for acute esophageal variceal bleeding; however, endoscopic injection sclerotherapy can be used in the acute setting if EBL is technically difficult.     

Cost-effectiveness analysis of transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic therapy for the prevention of recurrent esophageal variceal bleeding

For the prevention of recurrent esophageal variceal bleeding, studies show that patients treated with transjugular intrahepatic portosystemic shunt (TIPS) have lower rebleeding rates compared with endoscopic therapy. However, TIPS is associated with higher rates of portosystemic encephalopathy and possibly higher costs. The aim of this study was to conduct a cost-effectiveness analysis comparing TIPS with endoscopic sclerotherapy and endoscopic ligation for the prevention of recurrent esophageal variceal bleeding. Data for rates of rebleeding, death, complications, and crossover from endoscopy to TIPS were obtained from the literature. Costs for procedures and hospitalizations were obtained from two medical centers. Sensitivity analyses were performed varying probabilities of key variables. The patient population consisted of a hypothetical cohort of cirrhotic patients successfully treated for esophageal variceal bleeding with endoscopic sclerotherapy who received prophylactic sclerotherapy, ligation, or TIPS over 1 year. Endoscopic patients would receive propranolol. Mortality was similar for the three groups. The number of bleeds per patient for sclerotherapy, ligation, and TIPS would be 0.39, 0.32, and 0.07, respectively. The total annual costs per patient for sclerotherapy, ligation, and TIPS were $23,459, $23,111, and $26,275, respectively. The incremental cost per bleed prevented for TIPS compared with sclerotherapy and ligation was $8,803 and $12, 660, respectively. The incremental cost per bleed prevented for TIPS compared with sclerotherapy or ligation was sensitive to the cost of TIPS and the TIPS stenosis rate. Ligation had lower costs and lower recurrent bleeding rates than sclerotherapy. Compared with endoscopic therapy, TIPS leads to lower recurrent variceal bleeding rates and it is more cost effective in the short term for the prevention of recurrent esophageal variceal bleeding.     

Primary prophylaxis of variceal bleeding in patients with cirrhosis: A comparison of different strategies

Patients with cirrhosis and esophageal varices bleed at a yearly rate of 5%-15%, and, when variceal hemorrhage develops, mortality reaches 20%. Patients are deemed at high risk of bleeding when they present with medium or large-sized varices, when they have red signs on varices of any size and when they are classified as Child-Pugh C and have varices of any size. In order to avoid variceal bleeding and death, individuals with cirrhosis at high risk of bleeding must undergo primary prophylaxis, for which currently recommended strategies are the use of traditional non-selective beta-blockers (NSBBs) (i.e., propranolol or nadolol), carvedilol (a NSBB with additional alpha-adrenergic blocking effect) or endoscopic variceal ligation (EVL). The superiority of one of these alternatives over the others is controversial. While EVL might be superior to pharmacological therapy regarding the prevention of the first bleeding episode, either traditional NSBBs or carvedilol seem to play a more prominent role in mortality reduction, probably due to their capacity of preventing other complications of cirrhosis through the decrease in portal hypertension. A sequential strategy, in which patients unresponsive to pharmacological therapy would be submitted to endoscopic treatment, or the combination of pharmacological and endoscopic strategies might be beneficial and deserve further investigation.