Primary prophylaxis of variceal bleeding in cirrhotics unable to take beta-blockers: a randomized trial of ligation.

AIM: To compare endoscopic banding ligation vs. no treatment in cirrhotics with intolerance or contraindications to beta-blockers for prevention of first bleeding in portal hypertension. METHODS: A sample size of 214 was planned with all sizes of varices. However, the trial was stopped due to increased bleeding in 52 patients in the ligation group. The baseline severity liver disease and endoscopic features were similar. Ligation group: 25 (M/F = 21/4, mean age: 60 +/- 9.37 years); 27 not-treated group: 27 (M/F = 17/10, mean age: 63 +/- 10.27). RESULTS: The mean follow-up period was 19.5 +/- 13.3 months: five bled in the ligation group (20%), three from varices (two after banding at 11 and 17 days; one during the procedure), and two from gastropathy; two bled in the not-treated group (7%- two both varices) (P = 0.24). There were seven deaths in the ligation group and 11 in the not-treated group (P = 0.39). CONCLUSION: Sixty per cent of the bleeding in the banding group was probably iatrogenic, requiring the study to be stopped. Endoscopic banding ligation was no better than no treatment. This study suggests that ligation may be harmful when used as primary prophylaxis, similar to prophylactic sclerotherapy in the past.

Endoscopic sclerotherapy plus propranolol versus propranolol alone in the primary prevention of bleeding in high risk cirrhotic patients with esophageal varices: a prospective multicenter randomized trial.

BACKGROUND: Analysis of primary prevention studies of the use of beta-blockers has shown clear reductions in variceal bleeding in cirrhotic patients with varices. In contrast, the usefulness of prophylactic endoscopic sclerotherapy, alone or in combination with propranolol, in the management of these patients is still under investigation. The present study compared the efficacy of combined sclerotherapy and propranolol versus propranolol alone in the primary prevention of hemorrhage in cirrhotic patients with varices and high (greater than 18 mm Hg) intraesophageal variceal pressure. METHODS: Patients were randomly assigned to propranolol (42 patients) or to propranolol plus sclerotherapy (44 patients). The mean duration of follow-up was 26.8 +/- 7.7 and 24.6 +/- 9.8 months, respectively. RESULTS: During this period 23% of the patients in the combination group experienced at least 1 episode of bleeding due to varices or congestive gastropathy as compared with 14% in the propranolol group (not significant). Twenty-three patients (52%) in the combination group developed complications as compared with 8 (19%) in the propranolol group (p = 0.002). The mortality rate was similar in both groups (14% and 18%, respectively). The only independent factor predictive of survival was the level of serum albumin. CONCLUSIONS: Endoscopic sclerotherapy should not be used for the primary prevention of hemorrhage in cirrhotic patients at high risk of variceal bleeding who are undergoing treatment with propranolol.

Single portal pressure measurement predicts survival in cirrhotic patients with recent bleeding.

BACKGROUND: Height of portal pressure correlates with severity of alcoholic cirrhosis. Portal pressure indices are not however used routinely as predictors of survival. AIMS: To examine the clinical value of a single portal pressure measurement in predicting outcome in cirrhotic patients who have bled. METHODS: A series of 105 cirrhotic patients who consecutively underwent hepatic venous pressure measurement were investigated. The main cause of cirrhosis was alcoholic (64.8%) and prior to admission all patients had bled from varices. RESULTS: During the follow up period (median 566 days, range 10-2555), 33 patients died, and 54 developed variceal haemorrhage. Applying Cox regression analysis, hepatic venous pressure gradient, bilirubin, prothrombin time, ascites, and previous long term endoscopic treatment were the only statistically independent predictors of survival, irrespective of cirrhotic aetiology. The predictive value of the pressure gradient was much higher if the measurement was taken within the first or the second week from the bleeding and there was no association after 15 days. A hepatic venous pressure gradient of at least 16 mm Hg appeared to identify patients with a greatly increased risk of dying. CONCLUSIONS: Indirectly measured portal pressure is an independent predictor of survival in patients with both alcoholic and non-alcoholic cirrhosis. In patients with a previous variceal bleeding episode this predictive value seems to be better if the measurement is taken within the first two weeks from the bleeding episode. A greater use of this technique is recommended for the prognostic assessment and management of patients with chronic liver disease.

Bacterial infection is independently associated with failure to control bleeding in cirrhotic patients with gastrointestinal hemorrhage.

Bacterial infection is frequently diagnosed in cirrhotic patients with variceal hemorrhage. The aim of this study was to assess the incidence of failure to control bleeding in cirrhotic patients during the first 5 days after the episode of variceal bleeding in relation to the diagnosis of bacterial infection and use of antibiotics. One hundred seventy-seven consecutive admissions for gastrointestinal bleeding in 151 patients were evaluated prospectively. From them, 163 admissions for variceal bleeding in 137 patients were included in the main analysis. Bleeding was managed in a standardized protocol using octreotide or terlipressin with sclerotherapy or band ligation for active bleeding at endoscopy. The end points were defined as in Baveno guidelines related to transfusion requirement or fresh hematemesis after 6 hours from time zero. The standardized screening protocol for bacterial infection consisted of chest radiograph and blood, urine, and ascitic fluid cultures. Active bleeding was reported at endoscopy in 86 admissions (53%). Failure to control bleeding occurred in 76 patient admissions (47%). Empirical antibiotic treatment was used in 113 admissions (69%), whereas in 81% of them (91 admissions, 56%) 102 bacterial infections were documented. Multivariate analysis showed that proven bacterial infection (P < .0001) or antibiotic use (P < .003) as well as active bleeding at endoscopy (P < .001) and Child-Pugh score (P < .02) were independent prognostic factors of failure to control bleeding. The results remained unchanged when all patient admissions with gastrointestinal bleeding of any source were included in the multivariate analysis. Bacterial infection is associated with failure to control variceal bleeding and needs to be evaluated in the planning and analysis of clinical trials.

Factors related to early mortality after transjugular intrahepatic portosystemic shunt for failed endoscopic therapy in acute variceal bleeding.

BACKGROUND: Uncontrolled variceal haemorrhage is the main indication for transjugular intrahepatic portosystemic shunt. However, mortality is 50% for this high-risk group. We have evaluated clinical and laboratory variables prior to transjugular intrahepatic portosystemic shunt in order to establish predictors of mortality, validated prospectively. METHOD: Over a 4-year period, 367 patients were admitted with variceal bleeding. In 54 patients endoscopic therapy for acute variceal bleeding failed and they had emergency transjugular intrahepatic portosystemic shunt. Failure of therapy was defined as continued bleeding after 2 endoscopy sessions (n=39) or vasoconstrictor-resistant bleeding from gastric/ectopic varices (n=15). Thirty-three variables were analysed from data available immediately prior to transjugular intrahepatic portosystemic shunt. RESULTS: Twenty-six patients died within 6 weeks. In a multivariate analysis, 6 factors had independent prognostic value: moderate/severe ascites, requirement for ventilation, white cell blood count (WBC), platelet count (PLT), partial thromboplastin time with kaolin (PTTK) and creatinine. A prognostic index (PI) score was derived, in which presence of moderate/severe ascites, or need for ventilation, scored 1: PI=1.54 (Ascites)+1.27 (Ventilation)+1.38 Ln (WBC)+2.48 ln (PTTK)+1.55 Ln (Creat)-1.05 Ln (PLT). Using this equation, 42% (n=10) of deaths occurred in the fifth quintile (PI > or = 18.52), where the mortality was 100%. The score was prospectively validated in a further 31 patients, giving 100% positive predictive value. Eleven further patients died, including all seven with a PI >18.5. No survivors had a PI >18.3. CONCLUSION: Despite immediate control of bleeding by transjugular intrahepatic portosystemic shunt, patients with uncontrolled variceal haemorrhage have a high mortality, particularly when associated with markers of advanced liver disease, sepsis and multi-organ failure. The use of transjugular intrahepatic portosystemic shunt is probably not justified in this subgroup. Our prognostic index can help identify such patients, and, if validated elsewhere, will help in deciding when to use transjugular intrahepatic portosystemic shunt.

Endoscopic sclerotherapy versus variceal ligation in the long-term management of patients with cirrhosis after variceal bleeding. A prospective randomized study.

BACKGROUND/AIMS: Long-term endoscopic injection sclerotherapy of oesophageal varices prevents rebleeding in patients with cirrhosis surviving an acute variceal bleeding episode. However, this treatment is associated with a substantial complication rate. Endoscopic band ligation is a newly developed technique in an attempt to provide a safer alternative. The aim of this study was to compare the efficacy and safety of injection sclerotherapy versus variceal ligation in the management of patients with cirrhosis after variceal haemorrhage. METHODS: Seventy-seven patients with cirrhosis who proved to have oesophageal variceal bleeding were studied. After initial control of haemorrhage by sclerotherapy, 40 of the patients were randomly assigned to sclerotherapy and 37 to ligation. Both procedures were performed under midazolam sedation at intervals of 7-14 days until all varices in the distal oesophagus were eradicated or were too small to receive further treatment. RESULTS: The eradication of varices required a lower mean number of sessions with ligation (3.7 +/- 1.9) than with sclerotherapy (5.8 +/- 2.7, p = 0.002). The mean duration of follow-up was similar in both groups (15.6 months +/- 7.3 and 15 +/- 7.4, respectively). The proportion of patients remaining free from recurrent bleeding against time was significantly higher in the ligation group as compared to the sclerotherapy group (chi 2 = 3.86, p = 0.05). Only 13 patients (35%) developed complications in the ligation group as compared to 24 (60%, p = 0.05) in the sclerotherapy group. The mortality rate was similar in both groups (20% and 21%, respectively). CONCLUSIONS: Variceal ligation is better than sclerotherapy in the long-term management of patients with cirrhosis after variceal haemorrhage which was initially controlled with sclerotherapy.

Variceal and portal pressure measurement: techniques and applications.

Variceal and portal pressure measurements are currently the most widely used invasive techniques for the haemodynamic evaluation of portal hypertension in cirrhotic patients. Variceal pressure can be measured during endoscopy either directly by variceal puncture or indirectly by using a pressure sensitive gauge. More recently, an indirect technique which uses a plastic balloon attached to the end of the endoscope has been described. Variceal pressure appears to be an important risk factor for the occurrence of variceal haemorrhage as most studies concluded that variceal pressure tends to be higher in patients with previous bleeding than those without. Hepatic venous catheterization with measurements of the wedged and free hepatic pressures has become the method of choice in the estimation of portal pressure as it is a simple, fast and safe procedure, less invasive and more reproducible than the other techniques. Information obtained from hepatic vein catheterization gives a significant prognostic value in predicting survival. Despite the lack of a linear relationship between portal pressure and risk of variceal bleeding most prospective studies have concluded that the height of portal pressure is an important and independent predictive factor for bleeding. Hepatic venous catheterization is currently the best method of assessing the haemodynamic response to drug treatment and prediction of therapeutic response for the prevention of bleeding.

Somatostatin and octreotide in the management of acute variceal hemorrhage.

In recent years, somatostatin and its long-acting analogue octreotide have been used as the initial treatment in acute variceal hemorrhage, with conflicting results. The aim of this study was to meta-analyse all the randomised controlled trials published in English, in which somotostatin or octreotide was compared with other vasoactive drugs, balloon tamponade and endoscopic sclerotherapy in variceal hemorrhage. Concerning the control of bleeding, somatostatin or octreotide therapy was shown to be significantly better than the other vasoactive drugs (p < 0.0012, x2 = 10.55). In contrast, the effectiveness of both agents appeared to be similar to that of balloon tamponade and sclerotherapy in arresting acute variceal hemorrhage during the infusion period. Regarding the complication rate, it appears that treatment with somatostatin or octreotide is followed by a significantly lower complication rate as compared with the other vasoactive drugs (p < 0.0001, x2 = 16.47) as well as than endoscopic sclerotherapy (p, 0.0002, x2 = 14.16). In conclusion, the results of this study suggest that in acute variceal hemorrhage, somatostatin or octreotide is better than any other combination of vasoactive drugs. As regards comparison with sclerotherapy or balloon tamponade, further evidence of benefit is needed before a recommendation can be made for the use of instead of these two kind of treatments of the former procedures.

Balloon tamponade technique and efficacy in variceal haemorrhage.

BACKGROUND: The option of using direct compression to arrest haemorrhage from an oesophageal varix was introduced by Westphal in 1930. Since then, different types of oesophageal and or gastric balloons have become available for use. The published data concerning the efficacy and complications of the balloon tamponade in the treatment of variceal haemorrhage is evaluated. METHOD-RESULTS: Balloon tamponade as a single therapy may control initial variceal haemorrhage in more than 80% of cases. However, haemostasis is usually transient and is associated with a high rate of complications. As regards the comparison of balloon tamponade with vasoactive drugs such as vasopressin alone or vasopressin + terlipressin or terlipressin + nitroglycerin, it appears that both regimens are comparable in respect to initial control of bleeding, rebleeding, mortality, and complications. There is also evidence suggesting that balloon tamponade is as equally effective as octreotide and somatostatin in the initial control of variceal haemorrhage, but early rebleeding and complications are significantly less with the administration of both drugs. Finally, it appears that balloon tamponade is inferior to endoscopic sclerotherapy in both the acute and the long-term control of variceal haemorrhage. CONCLUSIONS: Balloon tamponade should be reserved for those patients with variceal haemorrhage in whom bleeding continues despite conservative treatment, or as the first form of treatment only if sclerotherapy is not available.