Original Article
Endoscopic Ligation Compared with Combined Treatment with Nadolol and Isosorbide Mononitrate to Prevent Recurrent Variceal Bleeding
N Engl J Med 2001; 345:647-655August 30, 2001
- Abstract
Background
After an episode of acute bleeding from esophageal varices, patients are at high risk for recurrent bleeding and death. We compared two treatments to prevent recurrent bleeding — endoscopic ligation and combined medical therapy with nadolol and isosorbide mononitrate.
Methods
We randomly assigned 144 patients with cirrhosis who were hospitalized with esophageal variceal bleeding to receive treatment with endoscopic ligation (72 patients) or the combined medical therapy (72 patients). Sessions of ligation were repeated every two to three weeks until the varices were eradicated. The mean (±SD) dose of nadolol was 96±56 mg per day, and the mean dose of isosorbide was 66±22 mg per day. The primary end points were recurrent bleeding, complications, and death.
Results
The median follow-up period was 21 months. A total of 35 patients in the ligation group and 24 in the medication group had recurrent bleeding. The probability of recurrence was lower in the medication group, both for all episodes related to portal hypertension (P=0.04) and for recurrent variceal bleeding (P=0.04). There were major complications in nine patients treated with ligation (seven had bleeding esophageal ulcers and two had aspiration pneumonia) and two treated with medication (both had bradycardia and dyspnea) (P=0.05). Thirty patients in the ligation group died, as did 23 patients in the medication group (P=0.52). The probability of recurrent bleeding was lower for patients with a hemodynamic response to therapy, defined as a decrease in the hepatic venous pressure gradient of more than 20 percent from the base-line value or to less than 12 mm Hg (18 percent, vs. 54 percent in patients with no hemodynamic response at one year; P<0.001), and the probability of survival was higher (94 percent vs. 78 percent at one year, P=0.02).
Conclusions
Combined therapy with nadolol and isosorbide mononitrate is more effective than endoscopic ligation for the prevention of recurrent bleeding and is associated with a lower rate of major complications.
Media in This Article
Figure 1
Actuarial Probability of Remaining Free of Any Recurrent Bleeding (Panel A) and Recurrent Variceal Bleeding (Panel B) in the Medication Group and in the Ligation Group.Figure 2
Actuarial Probability of Remaining Free of Recurrent Bleeding (Panel A) and of Survival (Panel B), According to the Presence or Absence of a Hemodynamic Response.Article Activity
- Article
After an episode of acute esophageal variceal bleeding, patients are at high risk for recurrent bleeding and death.1,2 Thus, therapy to prevent recurrent bleeding is essential.3 Endoscopic sclerotherapy is of proven benefit in such cases.4 However, it is associated with a rate of recurrent bleeding of up to 50 percent and with local and systemic complications such as fever, pain, pulmonary infections, and esophageal ulceration, stricture, and perforation. Some of these complications may be fatal.5 Endoscopic variceal ligation is a purely mechanical method of obliterating varices that was introduced to preclude the undesirable effects of sclerotherapy.6,7 Several studies have shown that, as compared with sclerotherapy, variceal ligation is safer, requires fewer sessions to obliterate varices, significantly reduces the rate of recurrent bleeding, and improves the probability of survival.8-10 Accordingly, endoscopic ligation is currently the preferred endoscopic treatment for preventing recurrent variceal bleeding.11
Randomized, controlled trials have shown that sclerotherapy is slightly more effective than nonselective beta-blockers for the prevention of recurrent bleeding, but that in patients treated endoscopically, severe complications are more common. There is no difference in survival.5 Hemodynamic studies have demonstrated that the use of nitrates in addition to beta-blockers leads to greater reductions in portal pressure12 and that such combined therapy is also effective in patients who do not have a response to beta-blockers alone.13 Combined treatment with nadolol and isosorbide mononitrate is associated with a significantly lower risk of recurrent bleeding and complications than sclerotherapy.14 In this study, we compared endoscopic ligation with treatment with nadolol plus isosorbide mononitrate for the prevention of recurrent variceal bleeding.
Methods
Selection of Patients
Between May 1994 and February 1999, 1318 patients were admitted to our hospital because of gastrointestinal bleeding. Of these, 233 patients with cirrhosis underwent emergency endoscopy within the first 24 hours after admission, and a hemorrhage from esophageal varices was identified. Cirrhosis was diagnosed on the basis of a previous liver biopsy or clinical, biochemical, and ultrasonographic findings.
A total of 83 patients were excluded from the trial because of an age of less than 18 years (2 patients), poor hepatic function as indicated by a Child–Pugh score greater than 12 (19 patients), advanced hepatocellular carcinoma (8 patients), associated conditions leading to a life expectancy of six months or less (6 patients), previous endoscopic therapy (16 patients), previous surgery to establish a shunt (2 patients), previous treatment with beta-blockers and isosorbide mononitrate (12 patients), and failure of medical therapy in controlling the index bleeding (18 patients). An additional six patients declined to participate in the study.
Randomization and Treatment
On their fifth day of hospitalization, the remaining 144 patients were randomly assigned to one of two treatment groups with the use of opaque, sealed envelopes that contained a treatment assignment derived from computer-generated random numbers. Randomization was stratified both according to the severity of liver failure (assessed by means of the Child–Pugh classification system [class A or B, indicating moderate failure, vs. class C, indicating severe failure]) and according to whether there was a history of previous variceal bleeding. Written informed consent was obtained from all the patients or their next of kin, and the trial was approved by the ethics committee of our hospital.
Continuous pharmacologic therapy was started immediately after randomization in the patients assigned to medical treatment. Nadolol was given orally at an initial dose of 80 mg once daily. The dose was subsequently adjusted over a period of five days to reduce the resting heart rate by 25 percent but not below 55 beats per minute. Oral isosorbide mononitrate was started immediately thereafter. Over the course of one week, the dose was progressively increased from 20 mg once a day at bedtime to 40 mg twice a day, unless side effects such as headache or hypotension (systolic blood pressure of less than 85 mm Hg) appeared, in which case we gave the maximal dose tolerated. Adherence to the regimen was assessed at each follow-up visit through careful questioning of the patient and his or her relatives.
Ligation was performed with the use of commercial devices — either a single band with an overtube or a multiband ligating device. Each varix was ligated at least once. Up to eight bands per session were placed within the lower esophagus. Sessions were conducted at the time of randomization, on day 7, and every two to three weeks thereafter until the varices had been eradicated. The varices were considered to have been eradicated when they had either disappeared or could not be grasped and banded by the ligator. Three months after the varices had been eradicated, follow-up endoscopy was performed and additional sessions of ligation were conducted if varices had reappeared; this process was repeated every six months thereafter.
Follow-up and End Points
The study continued until seven months after the enrollment of the last patient. The primary end points were recurrent bleeding, complications, and death.
Recurrent bleeding was defined as any episode of hematemesis, melena, or both that occurred during the follow-up period and was evaluated by emergency endoscopy. In both treatment groups, during the index hemorrhage as well as episodes of recurrent bleeding, patients were treated with somatostatin, emergency sclerotherapy, or both. Treatment failure was defined as the occurrence of two or more episodes of recurrent bleeding that required the transfusion of at least 2 units of red cells or a hemorrhage that continued despite medical treatment and required the transfusion of 4 or more units. Patients in whom the protocol treatment failed received an alternative treatment that was determined on a case-by-case basis.
Hemodynamic Studies
Hemodynamic studies were performed before randomization and again one to three months after the start of medical treatment or once the ligation treatments had been completed. After an overnight fast, a venous-catheter introducer was placed in the right femoral vein by the Seldinger technique and was used to advance, under fluoroscopic guidance, a 7-French balloon catheter into the right main hepatic vein and a Swan–Ganz catheter into the pulmonary artery. Portal pressure was measured as the hepatic venous pressure gradient. A hemodynamic response to therapy was defined as a decrease in the hepatic venous pressure gradient to less than 12 mm Hg or a decrease of more than 20 percent from the base-line value. Cardiopulmonary pressures and cardiac output were also measured. All measurements were performed in triplicate with the use of a previously calibrated strain-gauge transducer.
Statistical Analysis
The sample size was calculated on the assumption that there would be a 26 percent rate of recurrent bleeding in the medication group.14 In order to detect a difference between groups of at least 21 percent7 with use of a two-tailed test, at an alpha level of 0.05 and a beta level of 0.2, we required 70 patients in each treatment group.
All analyses were conducted according to the intention-to-treat principle. Qualitative variables were compared by means of Fisher's exact test. Student's t-test was used to compare continuous variables, and the Wilcoxon rank-sum test was used for skewed or ordinal data.15 Actuarial probabilities were calculated by the Kaplan–Meier method and compared with use of the log-rank test.16 Data were censored at the time of death or at the time of the last visit. The Cox proportional-hazards model was used to identify the variables that best explained the variability in the rates of survival and recurrent bleeding.17 All P values were two-tailed.15 Calculations were performed with the SPSS statistical software package (SPSS, Chicago).
Results
A total of 72 patients were randomly assigned to each treatment group. Base-line data were similar in the two groups (Table 1Table 1
Characteristics of Patients Treated with Nadolol plus Isosorbide Mononitrate or with Endoscopic Ligation, at Admission and during Follow-up. and Table 2Table 2
Changes in Hemodynamic Variables, Child–Pugh Scores, and Plasma Urea and Creatinine Levels in the Two Treatment Groups.). The median follow-up period was 21 months (Table 1). Six patients in the medication group had contraindications to nadolol and received only isosorbide mononitrate. There were no patients with contraindications to therapy with isosorbide mononitrate or to ligation. Four patients in the medication group did not adhere to the treatment regimen. Three patients in the ligation group declined further treatment. One stopped treatment after two sessions of ligation, and two stopped after three sessions.Recurrent Bleeding
The likelihood of recurrent bleeding was significantly lower in the medication group (Figure 1Figure 1
Actuarial Probability of Remaining Free of Any Recurrent Bleeding (Panel A) and Recurrent Variceal Bleeding (Panel B) in the Medication Group and in the Ligation Group.). The difference was also significant in an analysis that excluded the 12 patients in the medication group who did not receive nadolol because of contraindications (6 patients), complications (2 patients), or nonadherence (4 patients) and the 3 patients in the ligation group who declined to complete the treatment (P=0.01); 11 of these 15 patients (8 in the medication group and 3 in the ligation group) had recurrent bleeding episodes.When the analysis was stratified according to the Child–Pugh class of cirrhosis, the probability of recurrent bleeding at two years was 21 percent in the medication group and 43 percent in the ligation group among patients in class A (P=0.05), 33 percent and 50 percent, respectively, among patients in class B (P=0.15), and 53 percent and 63 percent, respectively, among patients in class C (P=0.64). The global P value for the analysis of recurrent bleeding according to the base-line Child–Pugh class was 0.04 by the log-rank test. Esophageal varices were the most frequent site of recurrent bleeding (Table 3Table 3
Episodes of Recurrent Bleeding in the Two Treatment Groups.). The probability of recurrent variceal bleeding was also lower in the medication group (Figure 1).In the Cox regression analysis, the treatment-group assignment was an independent predictor of the risk of recurrent bleeding (P=0.03), as were the presence or absence of a hemodynamic response (P<0.001) and the Child–Pugh score at the third month of follow-up (P=0.01).
The likelihood of treatment failure at two years was significantly lower in the medication group: 17 percent, as compared with 36 percent in the ligation group (P=0.04). Treatment failed in 12 patients in the medication group; 6 of these patients were then treated with endoscopic ligation, 3 received a transjugular intrahepatic portosystemic shunt, 1 received a portacaval shunt, and the remaining 2 received no further treatment because they had end-stage liver disease. In the ligation group, treatment failed in 23 patients; 8 of these patients were subsequently treated with nadolol and isosorbide mononitrate, 7 received a transjugular intrahepatic portosystemic shunt, 5 received a portacaval shunt, and the remaining 3 received no other treatment.
Survival
The actuarial probability of survival was similar in the two groups. At two years, the probability was 74 percent in the medication group and 65 percent in the ligation group (P=0.52). Thirty patients in the ligation group died, as did 23 in the medication group. Of these, 22 patients (12 in the ligation group and 10 in the medication group) died of liver failure. Death was related to recurrent bleeding in 14 patients (10 in the ligation group and 4 in the medication group) and to hepatocellular carcinoma in 13 patients (6 in the ligation group and 7 in the medication group); death was not related to cirrhosis in the remaining 4 patients. In the medication group, one patient died of cancer of the oropharynx and one of hemorrhagic stroke. In the ligation group, one patient died of pancreatic cancer and one of cardiovascular disease. Cox proportional-hazards regression analysis showed that a high Child–Pugh score at the third month of follow-up (P<0.001) and treatment failure (P=0.02) were independent predictors of death.
Complications and Secondary Outcome Measures
Severe treatment-related complications occurred in nine patients (12 percent) in the ligation group (seven had bleeding esophageal ulcers, and two had aspiration pneumonia), as compared with two patients (3 percent) in the medication group (both had bradycardia and dyspnea, and nadolol had to be discontinued) (P=0.05). In the ligation group, transient dysphagia occurred in five patients, postprocedural pain in six, and fever in two. In the medication group, weakness occurred in seven patients, headache in six, bradycardia in two, and impotence in two. Overall, complications occurred in 22 patients in the ligation group (31 percent) and in 19 in the medication group (26 percent, P=0.71). None of the complications were fatal.
At the time of the index endoscopy, six patients in each group had moderate portal hypertensive gastropathy. At the last endoscopy performed during follow-up, 13 patients in the ligation group, as compared with 4 in the medication group, had moderate or severe portal hypertensive gastropathy (P=0.03 for the comparison between treatment groups). Kidney function remained within the normal range in both groups, and variations were of similar magnitude (Table 2). During follow-up, ascites developed in 39 patients in the medication group (6 of whom had no history of ascites) and in 47 patients in the ligation group (4 of whom had no history of ascites) (P=0.23).
Hemodynamic Measurements
A total of 46 patients in the ligation group and 49 patients in the medication group underwent two hemodynamic studies each. In the remaining patients, the second study could not be conducted because of previous treatment failure or denial of consent.
Continued medical therapy, but not ligation, significantly reduced the hepatic venous pressure gradient (Table 2). Seven of the 46 patients in the ligation group with two measurements of the hepatic venous pressure gradient (15 percent) had a hemodynamic response, as did 25 of the 49 patients in the medication group with two measurements (51 percent, P<0.001). The hepatic venous pressure gradient decreased to less than 12 mm Hg in seven patients in the medication group and one in the ligation group (P=0.05).
In the medication group, recurrent bleeding occurred in 4 of the 25 patients with a measured hemodynamic response and in 16 of the 24 patients with no response; in the ligation group the comparable figures were 1 of 7 patients and 23 of 39 patients. The likelihood of recurrent bleeding at two years was significantly lower among patients with a hemodynamic response than among those with no response (Figure 2Figure 2
Actuarial Probability of Remaining Free of Recurrent Bleeding (Panel A) and of Survival (Panel B), According to the Presence or Absence of a Hemodynamic Response.), both in the medication group (19 percent vs. 62 percent, P=0.001) and in the ligation group (15 percent vs. 64 percent, P=0.05).Ascites developed in 6 of the 32 patients with a hemodynamic response, as compared with 42 of the 63 patients with no response (P<0.001). Eight of the 32 patients with a response had to be admitted to the hospital for reasons other than hemorrhage, as compared with 30 of the 63 patients with no response (P=0.04). At the third month of follow-up, the Child–Pugh score was lower among the patients with a hemodynamic response (6.1±1.8 vs. 7.1±2.0, P=0.01). The actuarial probability of survival was significantly higher among the patients with a hemodynamic response than among those with no response (P=0.02) (Figure 2). A total of 24 of the 63 patients with no hemodynamic response (38 percent) and 3 of the 32 patients with a response (9 percent) died. Stepwise logistic-regression analysis showed that the treatment-group assignment (P=0.01) and the Child–Pugh score at the third month of follow-up (P=0.05) were independent predictors of the likelihood of a hemodynamic response.
Discussion
The efficacy of variceal ligation, as found in our study, is consistent with the higher ranges previously reported in randomized trials of this treatment.18-20 A relatively wide variation in rates of recurrent bleeding has been observed with ligation.8-10,18-20 This variation may be due, at least in part, to technical differences among studies, such as variations in the interval between sessions or in the number of bands placed during each session.11 Whether these or other technical differences can affect the outcome has not been adequately investigated. Other possible confounding factors — such as the time since the initial bleeding episode, alcohol use or nonuse, and the treatment used to stop the bleeding — may also affect the results of treatment.2,3,21 Among different trials, there may be differences in the randomization process or in the characteristics of the population treated, such as the cause or the severity of cirrhosis,2 or in the definition of end points such as recurrent bleeding.3,22
Our study had few exclusion criteria; a high proportion of the patients had advanced liver disease; and randomization was performed soon after the initial episode of acute bleeding had been controlled. All the episodes of recurrent bleeding were evaluated, regardless of the severity or the source (even those of unknown origin were taken into account), and the treatment of both the index episode of bleeding and recurrent hemorrhages included emergency sclerotherapy instead of ligation. These factors may account for the relatively high rate of recurrent bleeding in the ligation group. Although this rate of recurrent bleeding may seem similar to our previous findings with sclerotherapy in a study with a similar design,14 the studies are not comparable. The current study had a longer follow-up period, and the patients were sicker, as indicated by factors such as higher portal pressure and higher Child–Pugh score at follow-up.
The efficacy of the combination of a beta-blocker and isosorbide mononitrate was similar to that previously reported.23 Our results suggest that once acute esophageal variceal bleeding has been controlled, this combined medical therapy has significant advantages over endoscopic ligation. Recurrent bleeding was significantly less common with the medical therapy — whether we considered all the episodes related to portal hypertension or only those caused by esophageal varices. The difference was more pronounced among patients whose liver function was well preserved. Furthermore, although the incidence of side effects was similar in the two treatment groups, the rate of major complications was significantly lower among patients who received medical therapy than among those treated with endoscopic ligation. With both treatments, the incidence and types of complications were similar to those reported in previous trials.11,23 As in previous studies,24,25 our results show that the combination of a beta-blocker and isosorbide mononitrate does not impair renal function or increase the risk of ascites. It has also been suggested that, as with sclerotherapy,5 variceal ligation may worsen the severity of portal hypertensive gastropathy.26 We found that this condition developed in patients treated with ligation significantly more often than in those treated with medications.
Combined therapy with beta-blockers plus isosorbide mononitrate was compared with endoscopic variceal ligation for the prevention of recurrent variceal bleeding in another study; its preliminary results are similar to ours.27 A recent randomized trial also suggests that the addition of isosorbide mononitrate to beta-blockers improves the efficacy of the beta-blockers in the prevention of recurrent variceal bleeding in patients with cirrhosis.28 Furthermore, no clear advantages have been noted in trials in which the use of a transjugular intrahepatic portosystemic shunt29 or invasive therapy (consisting of surgery to establish a shunt for patients in Child–Pugh class A or B, and sclerotherapy for patients with class C disease)30 has been compared with this combined medical therapy.
The higher efficacy we observed with medical therapy may be related to hemodynamic changes.31 Pharmacologic therapy aims to produce a sustained reduction in portal pressure.32 The response of portal pressure to treatment can be considered appropriate when the hepatic venous pressure gradient is reduced to less than 12 mm Hg or by more than 20 percent from the base-line value.31,33,34 The risk of variceal bleeding is extremely low when these targets are achieved.33,34 In our trial, the proportion of patients who had a hemodynamic response was significantly higher with medical therapy than with ligation. In both treatment groups, the probability of recurrent bleeding was significantly lower among patients who had a hemodynamic response than among those who did not. The probability of survival was also significantly higher among the patients with a hemodynamic response than among those with no response. A hemodynamic response was an independent predictor of the risk of recurrent bleeding, and treatment failure was an independent predictor of death.
In conclusion, in comparison with endoscopic ligation, we found that combined therapy with nadolol and isosorbide mononitrate significantly decreases the incidence of recurrent bleeding and of the major treatment-related complications of variceal hemorrhage. Our data suggest that monitoring of the hepatic venous pressure gradient identifies patients with a poor response, in whom more aggressive alternative therapies may be warranted.
Supported in part by a grant from the Fundació Investigació Sant Pau.
Source Information
From the Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Address reprint requests to Dr. Villanueva at the Servei de Patologia Digestiva, Hospital de la Santa Creu i Sant Pau, Avgda. Sant Antoni M. Claret, 167, 08025 Barcelona, Spain, or at cvillanueva@hsp.santpau.es.
- References
References
1
Graham DY ,Smith JL . The course of patients after variceal hemorrhage. Gastroenterology 1981;80:800-809
Web of Science | Medline2
Burroughs AK ,McCormick PA . Natural history and prognosis of variceal bleeding. Baillieres Clin Gastroenterol 1992;6:437-450
CrossRef | Web of Science | Medline3
Grace ND ,Groszmann RJ ,Garcia-Tsao G , et al. Portal hypertension and variceal bleeding: an AASLD single topic symposium. Hepatology 1998;28:868-880
CrossRef | Medline4
Balanzo J ,Such J ,Sainz S , et al. Long term survival and severe rebleeding after variceal sclerotherapy. Surg Gynecol Obstet 1990;171:489-492
Web of Science | Medline5
D'Amico G ,Pagliaro L ,Bosch J . The treatment of portal hypertension: a meta-analytic review. Hepatology 1995;22:332-354
CrossRef | Web of Science | Medline6
Van Stiegmann G ,Cambre T ,Sun JH . A new endoscopic elastic band ligating device. Gastrointest Endosc 1986;32:230-233
CrossRef | Web of Science | Medline7
Van Stiegmann G ,Goff JS ,Sun JH ,Hruza D ,Reveille RM . Endoscopic ligation of esophageal varices. Am J Surg 1990;159:21-26
CrossRef | Web of Science | Medline8
Stiegmann GV ,Goff JS ,Michaletz-Onody PA , et al. Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices. N Engl J Med 1992;326:1527-1532
Full Text | Web of Science | Medline9
Gimson AES ,Ramage JK ,Panos MZ , et al. Randomised trial of variceal banding ligation versus injection sclerotherapy for bleeding oesophageal varices. Lancet 1993;342:391-394
CrossRef | Web of Science | Medline10
Laine L ,el-Newihi HM ,Migikovsky B ,Sloane R ,Garcia F . Endoscopic ligation compared with sclerotherapy for the treatment of bleeding esophageal varices. Ann Intern Med 1993;119:1-7
Web of Science | Medline11
Laine L ,Cook D . Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding: a meta-analysis. Ann Intern Med 1995;123:280-287
Web of Science | Medline12
Garcia-Pagan JC ,Feu F ,Bosch J ,Rodes J . Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis: a randomized controlled study. Ann Intern Med 1991;114:869-873
Web of Science | Medline13
Merkel C ,Sacerdoti D ,Bolognesi M , et al. Hemodynamic evaluation of the addition of isosorbide-5-mononitrate to nadolol in cirrhotic patients with insufficient response to the β-blocker alone. Hepatology 1997;26:34-39
Web of Science | Medline14
Villanueva C ,Balanzo J ,Novella MT , et al. Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding. N Engl J Med 1996;334:1624-1629
Full Text | Web of Science | Medline15
Armitage P, Berry G. Statistical methods in medical research. 3rd ed. Oxford, England: Blackwell Scientific, 1994.
16
Altman DG. Practical statistics for medical research. London: Chapman & Hall, 1991.
17
Christensen E . Multivariate survival analysis using Cox's regression model. Hepatology 1987;7:1346-1358
CrossRef | Web of Science | Medline18
Jalan R ,Forrest EH ,Stanley AJ , et al. A randomized trial comparing transjugular intrahepatic portosystemic stent-shunt with variceal band ligation in the prevention of rebleeding from esophageal varices. Hepatology 1997;26:1115-1122
Web of Science | Medline19
Gralnek IM ,Jensen DM ,Kovacs TOG , et al. The economic impact of esophageal variceal hemorrhage: cost-effectiveness implications of endoscopic therapy. Hepatology 1999;29:44-50
CrossRef | Web of Science | Medline20
Lo GH ,Lai KH ,Cheng JS , et al. Endoscopic variceal ligation plus nadolol and sucralfate compared with ligation alone for the prevention of variceal rebleeding: a prospective, randomized trial. Hepatology 2000;32:461-465
CrossRef | Web of Science | Medline21
Burroughs AK ,Mezzanotte G ,Phillips A ,McCormick PA ,McIntyre N . Cirrhotics with variceal hemorrhage: the importance of the time interval between admission and the start of analysis for survival and rebleeding rates. Hepatology 1989;9:801-807
CrossRef | Web of Science | Medline22
de Franchis R ,Pascal JP ,Ancona E , et al. Definitions, methodology and therapeutic strategies in portal hypertension: a consensus development workshop, Baveno, Lake Maggiore, Italy, April 5 and 6, 1990. J Hepatol 1992;15:256-261
CrossRef | Web of Science | Medline23
D'Amico G ,Pagliaro L ,Bosch J . Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis 1999;19:475-505
CrossRef | Web of Science | Medline24
Morillas RM ,Planas R ,Cabre E , et al. Propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis: long-term hemodynamic and renal effects. Hepatology 1994;20:1502-1508
CrossRef | Web of Science | Medline25
Merkel C ,Gatta A ,Donada C , et al. Long-term effects of nadolol or nadolol plus isosorbide-5-mononitrate on renal function and ascites formation in patients with cirrhosis. Hepatology 1995;22:808-813
Web of Science | Medline26
de la Pena J ,Rivero M ,Sanchez E ,Fabrega E ,Crespo J ,Pons-Romero F . Variceal ligation compared with endoscopic sclerotherapy for variceal hemorrhage: prospective randomized trial. Gastrointest Endosc 1999;49:417-423
CrossRef | Web of Science | Medline27
Patch D ,Goulis J ,Gerunda G ,Merkel C ,Greenslade L ,Burroughs AK . A randomised controlled trial comparing wedge pressure guided medical therapy (MT) against variceal banding (VB) in the secondary prevention of variceal haemorrhage. J Hepatol 2000;32:Suppl 2:35-35 abstract.
CrossRef | Web of Science28
Gournay J ,Masliah C ,Martin T ,Perrin D ,Galmiche JP . Isosorbide mononitrate and propranolol compared with propranolol alone for the prevention of variceal rebleeding. Hepatology 2000;31:1239-1245
CrossRef | Web of Science | Medline29
Escorsell A ,Banares R ,Gilabert R , et al. Transjugular intrahepatic portosystemic shunt (TIPS) vs propranolol + isosorbide-mononitrate (P+I) for the prevention of variceal rebleeding in patients with cirrhosis: results of a randomized controlled trial. Hepatology 1998;28:Suppl:770A-770A abstract.
Web of Science30
McCormick PA ,Feu F ,Sabrin C ,Planas R . Propranolol and isosorbide mononitrate versus sclerotherapy or shunt surgery for the prevention of variceal rebleeding: a randomized trial. Hepatology 1994;20:Suppl:106A-106A abstract.
CrossRef | Web of Science31
Bosch J ,Garcia-Pagan JC . Complications of cirrhosis. I. Portal hypertension. J Hepatol 2000;32:Suppl 1:141-156
CrossRef | Web of Science | Medline32
Polio J ,Groszmann RJ . Hemodynamic factors involved in the development and rupture of esophageal varices: a pathophysiologic approach to treatment. Semin Liver Dis 1986;6:318-331
CrossRef | Web of Science | Medline33
Groszmann RJ ,Bosch J ,Grace ND , et al. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology 1990;99:1401-1407
Web of Science | Medline34
Feu F ,Garcia-Pagan JC ,Bosch J , et al. Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis. Lancet 1995;346:1056-1059
CrossRef | Web of Science | Medline
- Citing Articles (119)
Citing Articles
1
Hitoshi Maruyama, Arun J. Sanyal. 2011. Portal Hypertension: Nonsurgical and Surgical Management. , 326-361.
CrossRef2
Carlo Merkel, Sara Montagnese. (2011) Hepatic venous pressure gradient measurement in clinical hepatology. Digestive and Liver Disease 43:10, 762-767
CrossRef3
Antonio González, Salvador Augustin, Joan Dot, Mercedes Pérez, Monder Abu-Suboh, Alejandro Romero, Antoni Segarra, Josep Ramón Armengol, Rafael Esteban, Jaime Guardia, Joan Genescà. (2011) Adding banding ligation is effective as rescue therapy to prevent variceal rebleeding in haemodynamic non-responders to pharmacological therapy. Digestive and Liver Disease
CrossRef4
Ulrich Thalheimer, Christos Triantos, John Goulis, Andrew K Burroughs. (2011) Management of varices in cirrhosis. Expert Opinion on Pharmacotherapy 12:5, 721-735
CrossRef5
Norman Grace, Gin-Ho Lo, Frederik Nevens, Tilman Sauerbruch, Peter Hayes, Candid Villanueva, Didier Lebrec. 2011. Preventing Rebleeding in 2010. , 119-131.
CrossRef6
Naim Alkhouri, Charles Winans, Vera F. Hupertz. 2011. Portal Hypertension. , 829-839.
CrossRef7
L. L. Gluud, E. Langholz, A. Krag. (2010) Meta-analysis: isosorbide-mononitrate alone or with either beta-blockers or endoscopic therapy for the management of oesophageal varices. Alimentary Pharmacology & Therapeutics 32:7, 859-871
CrossRef8
Christos Triantos, John Goulis, Andrew K Burroughs. 2010. Portal Hypertensive Bleeding. , 562-602.
CrossRef9
Cecilia Miñano, Guadalupe Garcia-Tsao. (2010) Clinical Pharmacology of Portal Hypertension. Gastroenterology Clinics of North America 39:3, 681-695
CrossRef10
Puneeta Tandon, Rosa Saez, Annalisa Berzigotti, Juan G Abraldes, Juan Carlos Garcia-Pagan, Jaime Bosch. (2010) A Specialized, Nurse-Run Titration Clinic: A Feasible Option for Optimizing β-Blockade in Non–Clinical Trial Patients. The American Journal of Gastroenterology 105:9, 1917-1921
CrossRef11
Gin-Ho Lo. (2010) The Role of Endoscopy in Secondary Prophylaxis of Esophageal Varices. Clinics in Liver Disease 14:2, 307-323
CrossRef12
Enrique de-Madaria, José María Palazón, Flavia Tamara Hernández, José Sánchez-Paya, Pedro Zapater, Javier Irurzun, Francisco de España, Sonia Pascual, José Such, Laura Sempere, Fernando Carnicer, Antonio García-Herola, Jaime Valverde, Miguel Pérez-Mateo. (2010) Acute and chronic hemodynamic changes after propranolol in patients with cirrhosis under primary and secondary prophylaxis of variceal bleeding: a pilot study. European Journal of Gastroenterology & Hepatology 22:5, 507-512
CrossRef13
Michael J. Englesbe, James Kubus, Wajee Muhammad, Christopher J. Sonnenday, Theodore Welling, Jeffrey D. Punch, Raymond J. Lynch, Jorge A. Marrero, Shawn J. Pelletier. (2010) Portal vein thrombosis and survival in patients with cirrhosis. Liver Transplantation 16:1, 83-90
CrossRef14
Chang Hyeong Lee. (2010) Prevention of Esophageal Variceal Bleeding. The Korean Journal of Gastroenterology 56:3, 155
CrossRef15
Mamata Ravipati, Srikanth Katragadda, Paari Dominic Swaminathan, Janos Molnar, Edwin Zarling. (2009) Pharmacotherapy plus endoscopic intervention is more effective than pharmacotherapy or endoscopy alone in the secondary prevention of esophageal variceal bleeding: a meta-analysis of randomized, controlled trials. Gastrointestinal Endoscopy 70:4, 658-664.e5
CrossRef16
J. CHEUNG, M. ZEMAN, S. V. van ZANTEN, P. TANDON. (2009) Systematic review: secondary prevention with band ligation, pharmacotherapy or combination therapy after bleeding from oesophageal varices. Alimentary Pharmacology & Therapeutics 30:6, 577-588
CrossRef17
Càndid Villanueva, Carles Aracil, Alan Colomo, Virginia Hernández–Gea, Josep M. López–Balaguer, Cristina Alvarez–Urturi, Xavier Torras, Joaquim Balanzó, Carlos Guarner. (2009) Acute Hemodynamic Response to β-Blockers and Prediction of Long-term Outcome in Primary Prophylaxis of Variceal Bleeding. Gastroenterology 137:1, 119-128
CrossRef18
Sameer Parikh. (2009) Hepatic Venous Pressure Gradient: Worth Another Look?. Digestive Diseases and Sciences 54:6, 1178-1183
CrossRef19
Gin-Ho Lo, Wen-Chi Chen, Hoi-Hung Chan, Wei-Lun Tsai, Ping-I Hsu, Chiun-Ku Lin, Tai-An Chen, Kwok-Hung Lai. (2009) A randomized, controlled trial of banding ligation plus drug therapy versus drug therapy alone in the prevention of esophageal variceal rebleeding. Journal of Gastroenterology and Hepatology 24:6, 982-987
CrossRef20
Giovanni Galati, Umberto Vespasiani Gentilucci, Ilaria Sansoni, Sandro Spataro, Francesco M. Di Matteo, Enrico M. Zardi, Rosario F. Grasso, Giuseppe Avvisati, Antonella Afeltra, Antonio Picardi. (2009) A mocking finding: portal cavernoma mimicking neoplastic mass: first sign of myeloproliferative disorder in a patient with Janus kinase2 V617F mutation. European Journal of Gastroenterology & Hepatology 21:2, 233-236
CrossRef21
C. VILLANUEVA, C. ARACIL, A. COLOMO, J. M. LOPEZ-BALAGUER, M. PIQUERAS, B. GONZALEZ, X. TORRAS, C. GUARNER, J. BALANZO. (2009) Clinical trial: a randomized controlled study on prevention of variceal rebleeding comparing nadolol + ligation vs. hepatic venous pressure gradient-guided pharmacological therapy. Alimentary Pharmacology & Therapeutics 29:4, 397-408
CrossRef22
C. K. TRIANTOS, V. NIKOLOPOULOU, A. K. BURROUGHS. (2008) Review article: the therapeutic and prognostic benefit of portal pressure reduction in cirrhosis. Alimentary Pharmacology & Therapeutics 28:8, 943-952
CrossRef23
Gin-Ho Lo, Wen-Chi Chen, Chiun-Ku Lin, Wei-Lun Tsai, Hoi-Hung Chan, Tai-An Chen, Hsien-Chung Yu, Ping-I Hsu, Kwok-Hung Lai. (2008) Improved survival in patients receiving medical therapy as compared with banding ligation for the prevention of esophageal variceal rebleeding. Hepatology 48:2, 580-587
CrossRef24
J. C. GARCIA-PAGAN, A. DE GOTTARDI, J. BOSCH. (2008) Review article: the modern management of portal hypertension - primary and secondary prophylaxis of variceal bleeding in cirrhotic patients. Alimentary Pharmacology & Therapeutics 28:2, 178-186
CrossRef25
Guadalupe Garcia-Tsao, Jaime Bosch, Roberto J. Groszmann. (2008) Portal hypertension and variceal bleeding—Unresolved issues. Summary of an American Association for the study of liver diseases and European Association for the study of the liver single-topic conference. Hepatology 47:5, 1764-1772
CrossRef26
Nagib Toubia, Arun J. Sanyal. (2008) Portal Hypertension and Variceal Hemorrhage. Medical Clinics of North America 92:3, 551-574
CrossRef27
A. Berzigotti, J.C. García-Pagán. (2008) Prevention of recurrent variceal bleeding. Digestive and Liver Disease 40:5, 337-342
CrossRef28
R. González-Alonso, M. Rodríguez-Gandía, M. Rivero, A. Albillos Martínez. (2008) Tratamiento de la hipertensión portal en la cirrosis. Medicine - Programa de Formación Médica Continuada Acreditado 10:11, 691-701
CrossRef29
Arun J. Sanyal, Jaime Bosch, Andres Blei, Vincente Arroyo. (2008) Portal Hypertension and Its Complications. Gastroenterology 134:6, 1715-1728
CrossRef30
A. Dell'Era, R. de Franchis, F. Iannuzzi. (2008) Acute variceal bleeding: Pharmacological treatment and primary/secondary prophylaxis. Best Practice & Research Clinical Gastroenterology 22:2, 279-294
CrossRef31
Càndid Villanueva, Alan Colomo, Carlos Aracil, Carlos Guarner. (2008) Current endoscopic therapy of variceal bleeding. Best Practice & Research Clinical Gastroenterology 22:2, 261-278
CrossRef32
F.H. Klebl, J. Schölmerich. (2008) Future expectations in the prophylaxis of intestinal bleeding. Best Practice & Research Clinical Gastroenterology 22:2, 373-387
CrossRef33
S. van Riesen, D.K. Wasowicz-Kemps, M.G.H. Besselink, T.L. Bollen, J.A. Vos, M.G. Onaca, M.J.M. Segers. (2008) Massive portal vein thrombosis and kidney rupture following blunt abdominal trauma: A diagnostic and therapeutic dilemma. Injury Extra 39:2, 71-75
CrossRef34
Cándid Villanueva, Joaquim Balanzó. (2008) Variceal Bleeding. Drugs 68:16, 2303-2324
CrossRef35
Ulrich Thalheimer, Jaime Bosch, Andrew K. Burroughs. (2007) How to Prevent Varices From Bleeding: Shades of Grey—The Case for Nonselective β Blockers. Gastroenterology 133:6, 2029-2036
CrossRef36
David Kravetz. (2007) Prevention of Recurrent Esophageal Variceal Hemorrhage. Journal of Clinical Gastroenterology 41:Supplement 3, S318-S322
CrossRef37
Julio D. Vorobioff. (2007) Hepatic Venous Pressure in Practice. Journal of Clinical Gastroenterology 41:Supplement 3, S336-S343
CrossRef38
Guadalupe Garcia-Tsao. (2007) Preventing the Development of Varices in Cirrhosis. Journal of Clinical Gastroenterology 41:Supplement 3, S300-S304
CrossRef39
Erwin Biecker, Felix Roth, Jörg Heller, Hans H. Schild, Tilman Sauerbruch, Michael Schepke. (2007) Prognostic role of the initial portal pressure gradient reduction after TIPS in patients with cirrhosis. European Journal of Gastroenterology & Hepatology 19:10, 846-852
CrossRef40
Guadalupe Garcia-Tsao, Arun J. Sanyal, Norman D. Grace, William D. Carey, . (2007) Prevention and Management of Gastroesophageal Varices and Variceal Hemorrhage in Cirrhosis. The American Journal of Gastroenterology 102:9, 2086-2102
CrossRef41
Guadalupe Garcia-Tsao, Arun J. Sanyal, Norman D. Grace, William Carey, . (2007) Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 46:3, 922-938
CrossRef42
Barjesh Chander Sharma, Lise Lotte Gluud, Shiv Kumar Sarin, Barjesh Chander Sharma. 2007. Beta-blocker plus nitrates for secondary prevention of variceal bleeding. .
CrossRef43
J. Heller, B. Appenrodt, M. Schepke, T. Sauerbruch. (2007) Varizenblutung bei Patienten mit Leberzirrhose. Der Gastroenterologe 2:4, 238-245
CrossRef44
Agustín Albillos, Rafael Bañares, Mónica González, Cristina Ripoll, Rosario Gonzalez, Maria-Vega Catalina, Luis-Miguel Molinero. (2007) Value of the Hepatic Venous Pressure Gradient to Monitor Drug Therapy for Portal Hypertension: A Meta-Analysis. The American Journal of Gastroenterology 102:5, 1116-1126
CrossRef45
Ulrich Thalheimer, Gioacchino Leandro, Maria Mela, David Patch, Andrew K. Burroughs. (2007) Systematic Review of HVPG Measurement: Statistics Versus Clinical Applicability. Gastroenterology 132:3, 1201-1202
CrossRef46
M. Senzolo, P. Burra, E. Cholongitas, F. Lodato, L. Marelli, P. Manousou, D. Patch, G.C. Sturniolo, A.K. Burroughs. (2007) The transjugular route: The key hole to the liver world. Digestive and Liver Disease 39:2, 105-116
CrossRef47
David W. Orr, Phillip M. Harrison, John Devlin, John B. Karani, Pauline A. Kane, Nigel D. Heaton, John G. O’Grady, Michael A. Heneghan. (2007) Chronic Mesenteric Venous Thrombosis: Evaluation and Determinants of Survival During Long-Term Follow-up. Clinical Gastroenterology and Hepatology 5:1, 80-86
CrossRef48
Jörg Heller, Tilman Sauerbruch. (2007) Prevention of recurrent haemorrhage. Best Practice & Research Clinical Gastroenterology 21:1, 43-53
CrossRef49
M. Wadhawan, S. Dubey, B. C. Sharma, S. K. Sarin, S. K. Sarin. (2006) Hepatic Venous Pressure Gradient in Cirrhosis: Correlation with the Size of Varices, Bleeding, Ascites, and Child's Status. Digestive Diseases and Sciences 51:12, 2264-2269
CrossRef50
Gennaro D’Amico, Juan Carlos Garcia-Pagan, Angelo Luca, Jaime Bosch. (2006) Hepatic Vein Pressure Gradient Reduction and Prevention of Variceal Bleeding in Cirrhosis: A Systematic Review. Gastroenterology 131:5, 1611-1624
CrossRef51
Antonio González, Salvador Augustin, Mercedes Pérez, Joan Dot, Esteban Saperas, Alejandro Tomasello, Antoni Segarra, Josep Ramón Armengol, Joan Ramón Malagelada, Rafael Esteban, Jaime Guardia, Joan Genescà. (2006) Hemodynamic response–guided therapy for prevention of variceal rebleeding: An uncontrolled pilot study. Hepatology 44:4, 806-812
CrossRef52
Diego Rincon, Cristina Ripoll, Oreste Lo Iacono, Magdalena Salcedo, Maria V. Catalina, Emilio Alvarez, Oscar Nuñez, Ana M. Matilla, Gerardo Clemente, Rafael Bañares. (2006) Antiviral Therapy Decreases Hepatic Venous Pressure Gradient in Patients with Chronic Hepatitis C and Advanced Fibrosis. The American Journal of Gastroenterology 101:10, 2269-2274
CrossRef53
G. ROMERO, D. KRAVETZ, J. ARGONZ, C. VULCANO, A. SUAREZ, E. FASSIO, N. DOMINGUEZ, A. BOSCO, A. MUÑOZ, P. SALGADO, R. TERG. (2006) Comparative study between nadolol and 5-isosorbide mononitrate vs. endoscopic band ligation plus sclerotherapy in the prevention of variceal rebleeding in cirrhotic patients: a randomized controlled trial. Alimentary Pharmacology & Therapeutics 24:4, 601-611
CrossRef54
Markus Peck-Radosavljevic. (2006) Portal hypertension – old problem, new therapeutic solutions. Wiener Medizinische Wochenschrift 156:13-14, 397-403
CrossRef55
Thomas D. Boyer. (2006) Wedged hepatic vein pressure (WHVP): Ready for prime time. Hepatology 43:3, 405-406
CrossRef56
Juan Turnes, Juan Carlos Garcia-Pagan, Juan G. Abraldes, Manuel Hernandez-Guerra, Alessandra Dell'Era, Jaime Bosch. (2006) Pharmacological Reduction of Portal Pressure and Long-Term Risk of First Variceal Bleeding in Patients with Cirrhosis. The American Journal of Gastroenterology 101:3, 506-512
CrossRef57
Don C. Rockey. (2006) Pharmacologic therapy for gastrointestinal bleeding due to portal hypertension and esophageal varices. Current Gastroenterology Reports 8:1, 7-13
CrossRef58
Bego??a Gonzalez-Suarez, Carlos Guarner, Candid Villanueva, Josep Minana, German Soriano, Adolfo Gallego, Sergio Sainz, Xavier Torras, Xavier Cusso, Joaquim Balanzo. (2006) Pharmacologic treatment of portal hypertension in the prevention of community-acquired spontaneous bacterial peritonitis. European Journal of Gastroenterology & Hepatology 18:1, 49-55
CrossRef59
Dennis M. Jensen. (2006) Outcomes, effectiveness, tolerability, and direct costs of prophylactic variceal treatments. Hepatology 43:1, 197-198
CrossRef60
P. DEIBERT, Y.-O. SCHUMACHER, G. RUECKER, O. G. OPITZ, H. E. BLUM, M. ROSSLE, W. KREISEL. (2006) Effect of vardenafil, an inhibitor of phosphodiesterase-5, on portal haemodynamics in normal and cirrhotic liver - results of a pilot study. Alimentary Pharmacology and Therapeutics 23:1, 121-128
CrossRef61
Gavin C Harewood, Todd H Baron, Louis M Wong Kee Song. (2006) Factors predicting success of endoscopic variceal ligation for secondary prophylaxis of esophageal variceal bleeding. Journal of Gastroenterology and Hepatology 21:1, 237-241
CrossRef62
Atif Zaman, Naga Chalasani. (2005) Bleeding Caused by Portal Hypertension. Gastroenterology Clinics of North America 34:4, 623-642
CrossRef63
Groszmann, Roberto J., Garcia-Tsao, Guadalupe, Bosch, Jaime, Grace, Norman D., Burroughs, Andrew K., Planas, Ramon, Escorsell, Angels, Garcia-Pagan, Juan Carlos, Patch, David, Matloff, Daniel S., Gao, Hong, Makuch, Robert, . (2005) Beta-Blockers to Prevent Gastroesophageal Varices in Patients with Cirrhosis. New England Journal of Medicine 353:21, 2254-2261
Full Text64
Juan Carlos Garcia-Pagán, Jaime Bosch. (2005) Endoscopic band ligation in the treatment of portal hypertension. Nature Clinical Practice Gastroenterology & Hepatology 2:11, 526-535
CrossRef65
Cristina Ripoll, Rafael Bañares, Diego Rincón, María-Vega Catalina, Oreste Lo Iacono, Magdalena Salcedo, Gerardo Clemente, Oscar Núñez, Ana Matilla, Luis-Miguel Molinero. (2005) Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD Era. Hepatology 42:4, 793-801
CrossRef66
Geoffroy Vanbiervliet, Gilles Pomier-Layrargues, Pierre-Michel Huet. (2005) Diagnostic invasif de l’hypertention portale au cours des hépatopathies chroniques. Gastroentérologie Clinique et Biologique 29:10, 988-996
CrossRef67
Nina Dib, Anselme Konate, Frédéric Oberti, Paul Calès. (2005) Diagnostic non invasif de l’hypertension portale au cours de la cirrhose. Gastroentérologie Clinique et Biologique 29:10, 975-987
CrossRef68
Jose G. de la Mora-Levy, Todd H. Baron. (2005) Endoscopic management of the liver transplant patient. Liver Transplantation 11:9, 1007-1021
CrossRef69
Shiv K. Sarin, Manav Wadhawan, Rajesh Gupta, Hansa Shahi. (2005) Evaluation of Endoscopic Variceal Ligation (EVL) Versus Propanolol Plus Isosorbide Mononitrate/Nadolol (ISMN) in the Prevention of Variceal Rebleeding: Comparison of Cirrhotic and Noncirrhotic Patients. Digestive Diseases and Sciences 50:8, 1538-1547
CrossRef70
Patrick S Kamath, Vijay Shah. (2005) Does nadolol improve the efficacy of endoscopic variceal ligation in the treatment of variceal bleeding?. Nature Clinical Practice Gastroenterology & Hepatology 2:6, 254-255
CrossRef71
Manuel Hern??ndez-Guerra, Juan Carlos Garc??a-Pag??n, Jaime Bosch. (2005) Increased Hepatic Resistance. Journal of Clinical Gastroenterology 39:Supplement 2, S131-S137
CrossRef72
Rome Jutabha, Dennis M. Jensen, Paul Martin, Thomas Savides, Steven-Huy Han, Jeffrey Gornbein. (2005) Randomized study comparing banding and propranolol to prevent initial variceal hemorrhage in cirrhotics with high-risk esophageal varices. Gastroenterology 128:4, 870-881
CrossRef73
L. Ruiz-del-Árbol Olmos, P. Valer López-Fando. (2005) Medición de la presión portal: ¿parámetro clínico o herramienta de investigación?. Gastroenterología y Hepatología 28:4, 237-239
CrossRef74
Joaquin de la Pe
a, Enric Brullet, Eloy Sanchez-Hern
CrossRef75
G. J. M. Webster, A. K. Burroughs, S. M. Riordan. (2005) Review article: portal vein thrombosis - new insights into aetiology and management. Alimentary Pharmacology and Therapeutics 21:1, 1-9
CrossRef76
Erwin Biecker, Michael Schepke, Tilman Sauerbruch. (2005) The Role of Endoscopy in Portal Hypertension. Digestive Diseases 23:1, 11-17
CrossRef77
Jaime Bosch, Juan G. Abraldes. (2005) Variceal Bleeding: Pharmacological Therapy. Digestive Diseases 23:1, 18-29
CrossRef78
R. de Franchis, A. Dell’Era, F. Iannuzzi. (2004) Diagnosis and treatment of portal hypertension. Digestive and Liver Disease 36:12, 787-798
CrossRef79
VIJAY SHAH. (2004) Molecular mechanisms in the pathogenesis of cirrhotic portal hypertension: focus on nitric oxide. Journal of Gastroenterology and Hepatology 19:s7, S145-S149
CrossRef80
GIN-HO LO. (2004) Variceal bleed: secondary prophylaxis- drugs versus endoscopy. Journal of Gastroenterology and Hepatology 19:s7, S179-S182
CrossRef81
GILLES POMIER-LAYRARGUES. (2004) Hepatic venous pressure gradient measurement: is it mandatory in the management of portal hypertension?. Journal of Gastroenterology and Hepatology 19:s7, S158-S161
CrossRef82
Han-Chieh Lin, Ying-Ying Yang, Ming-Chih Hou, Yi-Tsau Huang, Fa-Yauh Lee, Shou-Dong Lee. (2004) Acute Administration of Carvedilol is More Effective than Propranolol Plus Isosorbide-5-Mononitrate in the Reduction of Portal Pressure in Patients with Viral Cirrhosis. The American Journal of Gastroenterology 99:10, 1953-1958
CrossRef83
A. Dell'era, J. Bosch. (2004) The relevance of portal pressure and other risk factors in acute gastro-oesophageal variceal bleeding. Alimentary Pharmacology and Therapeutics 20:s3, 8-15
CrossRef84
Vijay Shah, Kirsten H. Long. (2004) Modeling Our Way Toward the Optimal Management of Variceal Hemorrhage. The American Journal of Gastroenterology 99:7, 1289-1290
CrossRef85
Laura E. Targownik, Brennan M.R. Spiegel, Gareth S. Dulai, Hetal A. Karsan, Ian M. Gralnek. (2004) The Cost-Effectiveness of Hepatic Venous Pressure Gradient Monitoring in the Prevention of Recurrent Variceal Hemorrhage. The American Journal of Gastroenterology 99:7, 1306-1315
CrossRef86
Joel H. Rubenstein, Glenn M. Eisen, John M. Inadomi. (2004) A Cost-Utility Analysis of Secondary Prophylaxis for Variceal Hemorrhage. The American Journal of Gastroenterology 99:7, 1274-1288
CrossRef87
Juan Carlos Garcia-Pag
CrossRef88
Andrew K Burroughs, Ulrich Thalheimer, Maria Mela, David Patch. (2004) Reply. Hepatology 39:6, 1747-1747
CrossRef89
Guadalupe Garcia-Tsao. (2004) Portal hypertension. Current Opinion in Gastroenterology 20:3, 254-263
CrossRef90
Samer Gawrieh, Kia Saeian. (2004) Management of esophageal varices: An update from Digestive Disease Week and American Association for the Study of Liver Diseases 2003. Current Gastroenterology Reports 6:3, 206-209
CrossRef91
M. González García, A. Albillos Martínez, L. Ruiz del Árbol Olmos. (2004) Tratamiento de la hipertensión portal. Medicine - Programa de Formación Médica Continuada Acreditado 9:8, 494-503
CrossRef92
D. L. Raines, A. W. Dupont, M. R. Arguedas. (2004) Cost-effectiveness of hepatic venous pressure gradient measurements for prophylaxis of variceal re-bleeding. Alimentary Pharmacology and Therapeutics 19:5, 571-581
CrossRef93
Ulrich Thalheimer, Maria Mela, David Patch, Andrew K. Burroughs. (2004) Targeting portal pressure measurements: A critical reappraisal. Hepatology 39:2, 286-290
CrossRef94
Martin Rössle, Daniel Grandt. (2004) TIPS: an update. Best Practice & Research Clinical Gastroenterology 18:1, 99-123
CrossRef95
Thomas D. Boyer. (2004) Changing clinical practice with measurements of portal pressure. Hepatology 39:2, 283-285
CrossRef96
Pierre-Michel Huet, Gilles Pomier-Layrargues. (2004) The hepatic venous pressure gradient: ?Remixed and revisited?. Hepatology 39:2, 295-298
CrossRef97
David J Exon, S.C Sydney Chung. (2004) Endoscopic therapy for upper gastrointestinal bleeding. Best Practice & Research Clinical Gastroenterology 18:1, 77-98
CrossRef98
Gennaro D’Amico. (2004) The role of vasoactive drugs in the treatment of oesophageal varices. Expert Opinion on Pharmacotherapy 5:2, 349-360
CrossRef99
Ala I. Sharara. 2004. Variceal Bleeding. , 576-586.
CrossRef100
Atif Zaman. (2003) Current management of esophageal varices. Current Treatment Options in Gastroenterology 6:6, 499-507
CrossRef101
Kevin M Comar, Arun J Sanyal. (2003) Portal hypertensive bleeding. Gastroenterology Clinics of North America 32:4, 1079-1105
CrossRef102
Jean Pappas Molleston. (2003) Variceal Bleeding in Children. Journal of Pediatric Gastroenterology and Nutrition 37:5, 538-545
CrossRef103
P. Schiedermaier, L. Koch, B. Stoffel-Wagner, G. Layer, T. Sauerbruch. (2003) Effect of propranolol and depot lanreotide SR on postprandial and circadian portal haemodynamics in cirrhosis. Alimentary Pharmacology and Therapeutics 18:8, 777-784
CrossRef104
Drew B. Schembre. (2003) Endoscopic therapeutic esophageal interventions. Current Opinion in Gastroenterology 19:4, 394-399
CrossRef105
Guadalupe Garcia-Tsao. (2003) Portal hypertension. Current Opinion in Gastroenterology 19:3, 250-258
CrossRef106
Joel H. Rubenstein, John M. Inadomi. (2003) SECONDARY PROPHYLAXIS OF VARICEAL BLEEDING: SHOULD WE SHOOT RUBBER-BANDS OR PUSH PILLS?. Evidence-Based Gastroenterology 4:2, 61-62
CrossRef107
Rhys B Vaughan, Jaye PF Chin-Dusting. (2003) Current pharmacotherapy in the management of cirrhosis: focus on the hyperdynamic circulation. Expert Opinion on Pharmacotherapy 4:5, 625-637
CrossRef108
Jaume Bosch, Juan Carlos García-Pagán. (2003) Prevention of variceal rebleeding. The Lancet 361:9361, 952-954
CrossRef109
Ala I. Sharara, Don C. Rockey. (2003) Therapy for primary prophylaxis of varices: And, the winner is …?. Hepatology 37:2, 473-475
CrossRef110
Rafael Bañares, Eduardo Moitinho, Ana Matilla, Juan Carlos García-Pagán, José Luis Lampreave, Carlos Piera, Juan G. Abraldes, Alejandro De Diego, Agustín Albillos, Jaime Bosch. (2002) Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis. Hepatology 36:6, 1367-1373
CrossRef111
JUAN G ABRALDES, JAIME BOSCH. (2002) Novel approaches to treat portal hypertension. Journal of Gastroenterology and Hepatology 17:s3, S232-S241
CrossRef112
Jaime Bosch. (2002) A la carte or menu fixe: Improving pharmacologic therapy of portal hypertension. Hepatology 36:6, 1330-1332
CrossRef113
Christophe Bureau, Jean-Marie Péron, Laurent Alric, Joséphine Morales, Jér??me Sanchez, Karl Barange, Jean-Louis Payen, Jean-Pierre Vinel. (2002) “A la carte” treatment of portal hypertension: Adapting medical therapy to hemodynamic response for the prevention of bleeding. Hepatology 36:6, 1361-1366
CrossRef114
A BURROUGHS. (2002) Management of Portal Hypertension and Budd-Chiari Syndrome. Medicine 30:12, 69-72
CrossRef115
A. Sonnenberg, M. W. Gavin. (2002) General principles to enhance practice patterns in gastrointestinal endoscopy. Alimentary Pharmacology and Therapeutics 16:5, 1003-1009
CrossRef116
Rachael Harry, Julia Wendon. (2002) Management of variceal bleeding. Current Opinion in Critical Care 8:2, 164-170
CrossRef117
(2002) Scientific Surgery. British Journal of Surgery 89:2, 254-254
CrossRef118
(2002) Prevention of Recurrent Variceal Bleeding. New England Journal of Medicine 346:3, 209-210
Full Text119
Sharara, Ala I., Rockey, Don C., . (2001) Gastroesophageal Variceal Hemorrhage. New England Journal of Medicine 345:9, 669-681
Full Text
