Prevention Of Recurrent Variceal Bleeding Research Articles

Prevention of Recurrent Variceal Bleeding: Pharmacologic Measures

Pharmacologic prevention of recurrent variceal bleeding is effective, and trials comparing drug regimens with other treatments such as injection sclerotherapy and surgery are awaited. The mechanism whereby drugs such as propranolol reduce the risk of variceal hemorrhage is unclear, and this remains a limiting factor in our ability to screen for other effective drugs. The frequency of adverse reactions and compliance is a significant problem, emphasizing the importance of patient selection.

The effects of alcohol use on rebleeding and mortality in patients with alcoholic cirrhosis following variceal haemorrhage

The effect of continued alcohol intake on prognosis in alcoholic cirrhotics who have already bled from varices is controversial. To investigate the effect of alcohol intake on prognosis we studied 189 consecutive alcoholic cirrhotics admitted, for the first time, to the Royal Free Hospital with variceal bleeding. Sixty-six died within 30 days of admission and 23 were excluded from the study for other reasons. Of the 100 remaining 15 remained 'probably abstinent' over long-term follow-up, 29 drank occasionally and 56 continued to misuse/abuse alcohol. The percentage survival probability at 2 years was 66% in the probable abstainers, 68% in the occasional drinkers and 63% in the alcohol abuse/misuse group. There were no significant differences in either mortality or rebleeding rates between the three groups. A rebleeding index (designed to take account of the number of rebleeds per patient and the total length of follow-up) also failed to show any significant difference between the three groups. The Cox proportional hazard model was used to study the effect of the following factors on rebleeding and mortality; age, sex, alcohol use, Pugh's score, acute treatment received for initial variceal bleed and long-term treatment received for prevention of recurrent variceal haemorrhage. Pugh's score was significantly related to risk of death during follow-up (p = 0.0122), but none of the other factors was significantly related to risk of rebleeding or mortality. Using conventional methods to determine alcohol use we were unable to demonstrate significant effects of alcohol intake on rebleeding or mortality in alcoholic cirrhotics who had bled from oesophageal varices.

Prevention of recurrent variceal bleeding in alcoholic cirrhotic patients: prospective controlled trial of propranolol and sclerotherapy

We conducted a prospective randomized controlled study to evaluate the effectiveness of propranolol and sclerotherapy, compared to a control group, in the prevention of variceal rebleeding in alcoholic cirrhotic patients. Among the 79 patients included, the distribution of patients according to Child-Pugh classification was: A, 22%; B, 40%; and C, 38%. Propranolol was given twice daily with a mean final dose of 54 +/- 16 mg/day, this resulted in a mean reduction in resting heart rate of 26 +/- 7%. Sclerotherapy was performed weekly using 1% polidocanol. End points were rebleeding or death. During the mean follow up of 19 +/- 16 months, 43 patients bled and 22 patients died. The cumulative percentages of patients free of rebleeding at 1 year were: propranolol, 81% (95% confidence interval (CI): 63-92); sclerotherapy, 64% (95% CI: 45-82); control, 54% (95% CI: 36-71); these differences did not reach statistical significance. The cumulative percentages of patients alive at 1 year were: propranolol, 92% (95% CI: 76-98); sclerotherapy, 79% (95% CI: 58-91); control, 81% (95% CI: 60-93); these differences were not statistically significant. Alcohol withdrawal, which occurred in 66% of patients, was an independent predictive factor associated with a decreased risk of rebleeding or death. In conclusion, a life table analysis of patients free of rebleeding, as well as of patients surviving, revealed a tendency in favour of propranolol. The lack of a statistical support for these two favorable effects could be due to poor statistical power.(ABSTRACT TRUNCATED AT 250 WORDS)

Nodular regenerative hyperplasia of the liver: an important cause of portal hypertension in non-cirrhotic patients

In our hospital over the last 10 years a diagnosis of nodular regenerative hyperplasia was made for 12 patients. Sixty-nine percent of these patients had portal hypertension, representing 27% of all our patients with portal hypertension and a noncirrhotic liver. Nodular regenerative hyperplasia was the second most frequent cause of portal hypertension in patients without cirrhosis. To make the diagnosis, a reticulin staining of a surgical biopsy is most helpful. However, the characteristic derangement of the liver architecture on histology may still be overlooked. In this study a suggestive relation was found between malignant disease (multiple myeloma, chronic myelogenous leukaemia, Leydig cell tumour and Hodgkin's disease), the use of cytotoxic or immunosuppressive drugs and nodular regenerative hyperplasia. Furthermore, a high rate of symptomatic nodular regenerative hyperplasia was observed in patients following kidney transplantation. Liver function abnormalities developed in these patients after a period ranging from 8 months to 3 years of immunosuppressive-or chemotherapy. These liver function abnormalities were, however, usually mild. Since hepatic encephalopathy is not likely to develop in these patients with nodular regenerative hyperplasia a decompressive shunt operation is a good alternative approach, if not the treatment of choice, for the prevention of recurrent variceal haemorrhage.

A hepatologist's view of variceal bleeding

Patients with cirrhosis and esophagogastric varices have a 25% to 33% risk of initial variceal bleeding, a risk of up to 70% for recurrent variceal bleeding, and an associated mortality of up to 50%. Based on a review of prospective randomized trials, control of acute variceal bleeding should involve vasopressin plus nitroglycerin as indicated for minor bleeding episodes, sclerotherapy for more severe bleeding episodes, and staple transection of the esophagus for patients who do not respond to these initial measures. Emergency portasystemic shunt surgery cannot be recommended at this time. For prevention of recurrent variceal hemorrhage, the data support the use of nonselective beta-adrenergic blockers (propranolol or nadolol) for patients with good liver function (Child's class A and B) and the use of chronic sclerotherapy to obliterate esophageal varices for patients with decompensated cirrhosis (Child's class C). Surgical procedures should be reserved for failures of medical management. The use of beta-adrenergic blockers offers the most promise for prevention of initial variceal bleeding.

A controlled trial of oral propranolol compared with injection sclerotherapy for the long-term magnagement of variceal bleeding

This trial was carried out to assess the value of propranolol for the prevention of recurrent variceal bleeding in patients with well-compensated cirrhosis. We also compared propranolol therapy to long-term injection sclerotherapy. One hundred and eight patients, in whom the original variceal hemorrhage stopped spontaneously (before diagnostic endoscopy) and without sclerotherapy or surgical intervention, were included. All were Pugh grade A or B; 55% had alcoholic cirrhosis. Patients were chosen randomly to receive oral propranolol (in a dosage to reduce resting pulse rate by 25%) or to undergo long-term injection sclerotherapy. In both groups, episodes of repeat bleeding that did not stop spontaneously were managed with sclerotherapy. Patients considered to have failed propranolol therapy were treated with long-term sclerotherapy. Follow-up ranged from 12 to 64 mo. In the propranolol group, 28 (54%) of the 52 patients had repeat bleeding from varices with a total of 57 episodes; 14 received long-term sclerotherapy. In the sclerotherapy group, 25 (45%) of the 56 patients had repeat bleeding, with a total of 40 episodes (p less than 0.20). On an intention-to-treat basis, the risk of bleeding expressed per patient-month of follow-up was similar for the two groups, at 0.05 and 0.037, respectively. Survival as assessed by cumulative life analysis was also similar, with 55% and 66% alive at 3 yr (p less than 0.40). Stepwise regression analysis of possible factors predicting further bleeding in patients taking propranolol selected only two variables--the pretreatment pulse rate and the extent of pulse-rate reduction in response to propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of Recurrent Variceal Bleeding—Is Surgical Rescue the Answer?

Excerpt Bleeding from esophageal varices continues to be a major complication of cirrhosis and portal hypertension, with the mortality for a bleeding episode close to 50% (1). Although the risk for...

Endoscopic Variceal Sclerosis Compared with Distal Splenorenal Shunt To Prevent Recurrent Variceal Bleeding in Cirrhosis

To define the roles of endoscopic variceal sclerosis and distal splenorenal shunt in the prevention of recurrent variceal bleeding in patients with cirrhosis. A prospective, randomized clinical trial with crossover for those failing therapy. The median follow-up was 61 months. A private, tertiary-referral university hospital. Seventy-two patients fulfilling inclusion criteria were drawn from a total of 420 patients treated during a 4.5-year interval. Endoscopic variceal sclerosis or distal splenorenal shunt. Survival was significantly (P = 0.02) improved in patients randomly assigned to receive sclerotherapy: 13 of these 37 (35%) patients failed sclerotherapy and required surgical rescue. A survival advantage (P = 0.01) was seen in patients with alcoholic cirrhosis who had this combined therapy; however, in patients with nonalcoholic cirrhosis, survival for those receiving sclerotherapy and surgical rescue was not significantly (P = 0.36) different from that of patients receiving distal splenorenal shunt. Control of variceal bleeding was significantly (P less than 0.001) better in the distal splenorenal shunt group (34 of 35 [97%] compared with 15 of 37 [41%] in the sclerotherapy group). Using death, uncontrolled rebleeding, or shunt thrombosis as the endpoints resulted in no significant difference between treatment groups. Hepatocyte function and portal perfusion were significantly better maintained in patients with alcoholic cirrhosis who were managed by sclerotherapy rather than shunt (P = 0.01 and P = 0.001, respectively). Endoscopic sclerotherapy with surgical rescue for uncontrolled bleeding is the optimum therapy for patients with alcoholic cirrhosis and variceal bleeding. Survival is similar in nonalcoholic patients treated with either distal splenorenal shunt or endoscopic sclerotherapy, but shunting provides better control of variceal bleeding.

Propranolol in the prevention of recurrent variceal hemorrhage in cirrhotic patients: A controlled trial

A double-blind controlled study of long-acting propranolol in the secondary prevention of variceal hemorrhage was conducted in 81 cirrhotic patients. After the index hemorrhage, all patients were treated with injection sclerotherapy on one occasion to secure hemostasis and then randomized within 72 h to propranolol or placebo therapy which was continued for 2 yr. Study endpoints were severe recurrence of variceal hemorrhage or death. Forty-two patients did not fulfill the entry criteria for the study. Thirty-eight patients received propranolol of whom 18 (47%) had further hemorrhage, 14 died, eight had side-effects (2 withdrawals), and 3 did not complete follow-up. Forty-three patients received placebo of whom 33 (77%) had further hemorrhage, 19 died, 5 had side-effects (2 withdrawals), and 5 failed to complete follow-up. The median time from onset of hemorrhage to starting drug therapy was 6 days for both groups. Life table analysis showed an equivalent incidence of further hemorrhage in both groups over the first 60 days, following which the propranolol group did consistently better than the placebo group. There was a significantly lower incidence of rebleeding in modified Child's C patients receiving propranolol (39%) than those on placebo (90%). No statistically significant effect on mortality was seen. In this study, propranolol reduced the incidence of late recurrence of variceal hemorrhage in patients with cirrhosis.

Prospective controlled trial of elective endoscopic sclerotherapy in comparison with percutaneous transhepatic obliteration of esophageal varices in patients with nonalcoholic cirrhosis

The results of a prospective randomized controlled trial of elective endoscopic intravariceal sclerotherapy carried out over a 36-mo period in comparison with elective percutaneous transhepatic obliteration of varices (PTO, are presented. Sixty-six patients with nonalcoholic cirrhosis were randomized after they had stabilized, usually between 7 and 14 days after variceal bleeding had stopped following medical treatment (balloon tamponade and vasopressin infusion). Thirty-three patients were assigned to the sclerotherapy group and the other 33 patients were assigned to the PTO group. The mean follow-up period was similar in both groups. There was no significant difference in demographic, clinical, and laboratory data between the two groups. Six patients (18%) in the sclerotherapy group and 21 (64%) in the PTO group had at least one episode of gastrointestinal bleeding during the follow-up period (p < 0.005). Three patients in the sclerotherapy group and 1 patient in the PTO group bled from lesions other than varices; therefore the incidence of variceal bleeding was 9% in the former and 61% in the latter (p < 0.005). The cumulative variceal bleeding rate was significantly lower in the sclerotherapy group than the PTO group (p < 0.05). Five patients in the sclerotherapy group died during the follow-up period but none died of recurrent variceal bleeding. Nineteen patients in the PTO group died and 10 of them died of bleeding from varices. The cumulative survival rate was significantly better in the sclerotherapy group (p < 0.05). These results indicate that elective endoscopic intravariceal sclerotherapy is superior to elective PTO in the prevention of recurrent variceal hemorrhage and mortality in nonalcoholic cirrhosis.

The Prevention of Recurrent Variceal Haemorrhage by Chronic Injection Sclerotherapy

Forty eight patients who have survived admission with acute variceal haemorrhage have been readmitted and entered into a programme of chronic injection sclerotherapy to prevent recurrent variceal haemorrhage. Two hundred and nineteen elective courses of injections were performed at fibreoptic endoscopy with minor complications occurring in six patients. Twenty three patients rebled on 33 occasions but in only five instances did haemorrhage occur following variceal obliteration. With 67 per cent of patients surviving one year, this treatment option offers a satisfactory means of preventing recurrent haemorrhage when variceal obliteration is achieved.

12 - Prevention of Recurrent Variceal Bleeding: Non-surgical Procedures

Patients with cirrhosis, who have survived an episode of variceal bleeding, often have far-advanced liver disease and therefore, on average, a severely restricted life expectancy. Still, the prognosis for the individual patient varies greatly depending on the presence or absence of large varices and the Child classification. Centres evaluating treatment of variceal bleeding often attract different patient populations. Comparison of the outcome of the complete series of patients is usually meaningless since results reflect the composition of the patient population rather than the applied therapy. The natural history of patients with variceal bleeding should be defined by Child category, allowing more precise definition of the therapeutic aims and subsequently assessment of the results. Persistent lowering of the portal pressure by pharmacological modulation of the portal haemodynamic system is now feasible due to the availability of long-acting oral medication. Propranolol is still the leading drug and, in one centre, its use in predominantly Child A patients was associated with a marked reduction in recurrent gastrointestinal bleeding and subsequently mortality rate. These results could not be reproduced in another centre. Both the restricted indication as well as the uncertain efficacy limit the current use of propranolol, but further pharmacological developments are bound to appear. Endoscopic sclerotherapy has become the treatment of choice in the prevention of recurrent variceal haemorrhage. The proponents of paravasal injection report excellent efficacy in combination with a low incidence of side-effects, whereas mainly theoretical reasons are advanced by users of intravariceal injections. Still, variceal haemorrhage remains an important clinical problem in the period between the start of sclerotherapy and the eradication of varices. Combination of sclerotherapy with portal antihypertensive medication might become the treatment of choice until eradication of varices has been achieved; thereafter either continued medication or repeated endoscopy will maintain an avariceal state and effective prevention of recurrent variceal bleeding.

13 - Prevention of Recurrent Variceal Bleeding: Surgical Procedures

Anastomoses portocaves de differents types. Abord direct des varices œsophagiennes. Operations diverses. Particularites de l'hypertension portale extra-hepatique

Controlled Trial of Propranolol for the Prevention of Recurrent Variceal Hemorrhage in Patients with Cirrhosis

We conducted a prospective randomized trial of propranolol for the prevention of recurrent variceal bleeding in 48 patients with cirrhosis of the liver. During a follow-up period of up to 21 months, 12 of 26 patients in the propranolol group and 11 of 22 in the control group had rebleeding from esophageal varices. There was no significant difference in rebleeding between the two groups. This contrasts with a previous report of the efficacy of propranolol in preventing recurrent gastrointestinal bleeding in alcoholic cirrhosis. The difference in results may be due to the inclusion in our study of patients with other causes of cirrhosis and more severe liver disease. Propranolol may not be indicated for the prophylaxis of variceal rebleeding in such patients, and we advocate that its use be limited at present to controlled clinical trials.