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      Recent advances in the management of variceal bleeding

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          Abstract

          Acute haemorrhage from ruptured gastroesophageal varices is perhaps the most serious consequence of uncontrolled portal hypertension in cirrhotic patients. It represents a medical emergency and is associated with a high morbidity and mortality. In those who survive the initial bleeding event, the risks of further bleeding and other decompensated events remain high. The past 30 years have seen a slow evolution of management strategies that have greatly improved the chances of surviving a variceal haemorrhage. Liver cirrhosis is a multi-staged pathological process and we are moving away from a one-size-fits-all therapeutic approach. Instead there is an increasing recognition that a more nuanced approach will yield optimal survival for patients. This approach seeks to risk stratify patients according to their disease stage. The exact type and timing of treatment offered can then be varied to suit individual patients. At the same time, the toolbox of available therapy is expanding and there is a continual stream of emerging evidence to support the use of endoscopic and pharmacological therapies. In this review, we present a summary of the treatment options for a variety of different clinical scenarios and for when there is failure to control bleeding. We have conducted a detailed literature review and presented up-to-date evidence from either primary randomized–controlled trials or meta-analyses that support current treatment algorithms.

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          Transfusion strategies for acute upper gastrointestinal bleeding.

          The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy. We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis. A total of 225 patients assigned to the restrictive strategy (51%), as compared with 61 assigned to the liberal strategy (14%), did not receive transfusions (P<0.001) [corrected].The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy. As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding. (Funded by Fundació Investigació Sant Pau; ClinicalTrials.gov number, NCT00414713.).
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            Prevalence, classification and natural history of gastric varices: a long-term follow-up study in 568 portal hypertension patients.

            To determine the prevalence and natural history of gastric varices, we prospectively studied 568 patients (393 bleeders and 175 nonbleeders) with portal hypertension (cirrhosis in 301 patients, noncirrhotic portal fibrosis in 115 patients, extrahepatic portal vein obstruction in 117 patients and hepatic venous outflow obstruction in 35 patients). Primary (present at initial examination) gastric varices were seen in 114 (20%) patients; more were present in bleeders than in non-bleeders (27% vs. 4%, respectively; p < 0.001). Secondary (occurring after obliteration of esophageal varices) gastric varices developed in 33 (9%) patients during follow-up of 24.6 +/- 5.3 mo. Gastric varices (compared with esophageal varices) bled in significantly fewer patients (25% vs. 64%, respectively). Gastric varices had a lower bleeding risk factor than did esophageal varices (2.0 +/- 0.5 vs. 4.3 +/- 0.4, respectively) but bled more severely (4.8 +/- 0.6 vs. 2.9 +/- 0.3 transfusion units per patient, respectively). Once a varix bled, mortality was more likely (45%) in gastric varix patients. Gastric varices were classified as gastroesophageal or isolated gastric varices. Type 1 gastroesophageal varices (lesser curve varices) were the most common (75%). After obliteration of esophageal varices, type 1 gastroesophageal varices disappeared in 59% of patients and persisted in the remainder; bleeding from persistent gastroesophageal varices was more common than it was from gastroesophageal varices that were obliterated (28% vs. 2%, respectively; p < 0.001). Type 2 gastroesophageal varices, which extend to greater curvature, bled often (55%) and were associated with high mortality. Type 1 isolated gastric varices patients had only fundal varices, with a high (78%) incidence of bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)
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              Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators.

              Several treatments have been proven to be effective for variceal bleeding in patients with cirrhosis. The aim of this multicenter, prospective, cohort study was to assess how these treatments are used in clinical practice and what are the posttherapeutic prognosis and prognostic indicators of upper digestive bleeding in patients with cirrhosis. A training set of 291 and a test set of 174 bleeding cirrhotic patients were included. Treatment was according to the preferences of each center and the follow-up period was 6 weeks. Predictive rules for 5-day failure (uncontrolled bleeding, rebleeding, or death) and 6-week mortality were developed by the logistic model in the training set and validated in the test set. Initial treatment controlled bleeding in 90% of patients, including vasoactive drugs in 27%, endoscopic therapy in 10%, combined (endoscopic and vasoactive) in 45%, balloon tamponade alone in 1%, and none in 17%. The 5-day failure rate was 13%, 6-week rebleeding was 17%, and mortality was 20%. Corresponding findings for variceal versus nonvariceal bleeding were 15% versus 7% (P =.034), 19% versus 10% (P =.019), and 20% versus 15% (P =.22). Active bleeding on endoscopy, hematocrit levels, aminotransferase levels, Child-Pugh class, and portal vein thrombosis were significant predictors of 5-day failure; alcohol-induced etiology, bilirubin, albumin, encephalopathy, and hepatocarcinoma were predictors of 6-week mortality. Prognostic reassessment including blood transfusions improved the predictive accuracy. All the developed prognostic models were superior to the Child-Pugh score. In conclusion, prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades. Initial treatment stops bleeding in 90% of patients. Accurate predictive rules are provided for early recognition of high-risk patients.
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                Author and article information

                Journal
                Gastroenterol Rep (Oxf)
                Gastroenterol Rep (Oxf)
                gastro
                Gastroenterology Report
                Oxford University Press
                2052-0034
                May 2017
                07 April 2017
                07 April 2017
                : 5
                : 2
                : 113-126
                Affiliations
                Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, UK
                Author notes
                [* ] Corresponding author. Liver Unit, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2TH, UK. Tel: +44-121–371–4645; Fax: +44-121–414–1833; Email: Dhiraj.Tripathi@ 123456uhb.nhs.uk
                Article
                gox007
                10.1093/gastro/gox007
                5421505
                28533909
                286e85c5-bbb3-456b-9bd9-1c34c6602fbd
                © The Author(s) 2017. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-Sen University.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.

                History
                : 21 February 2017
                : 22 February 2017
                Page count
                Pages: 14
                Categories
                Review Articles

                varices,acute varices haemorrhage,cirrhosis,prophylaxis,non-selective beta-blockers,variceal band ligation

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