Historical overview and review of current day treatment in the management of acute variceal haemorrhage

Variceal haemorrhage is one of the most devastating consequences of portal hypertension, with a 1-year mortality of 40%. With the passage of time, acute management strategies have developed with improved survival. The major historical treatment landmarks in the management of variceal haemorrhage can be divided into surgical, medical, endoscopic and radiological breakthroughs. We sought to provide a historical overview of the management of variceal haemorrhage and how treatment modalities over time have impacted on clinical outcomes. A PubMed search of the following terms: portal hypertension, variceal haemorrhage, gastric varices, oesophageal varices, transjugular intrahepatic portosystemic shunt was performed. To complement this, Google™ was searched with the aforementioned terms. Other relevant references were identified after review of the reference lists of articles. The review of therapeutic advances was conducted divided into pre-1970s, 1970/80s, 1990s, 2000-2010 and post-2010. Also, a summary and review on the pathophysiology of portal hypertension and clinical outcomes in variceal haemorrhage was performed. Aided by the development of endoscopic therapies, medication and improved radiological interventions; the management of variceal haemorrhage has changed over recent decades with improved survival from an often-terminating event in recent past.

Mortality and rebleeding following variceal haemorrhage in liver cirrhosis and periportal fibrosis

AIMTo investigate mortality and rebleeding rate and identify associated risk factors at 6 wk and 5 d following acute variceal haemorrhage in patients with liver cirrhosis and schistosomal periportal fibrosis. METHODSThis is a prospective study conducted during the period from March to December 2014. Patients with portal hypertension presenting with acute variceal haemorrhage secondary to either liver cirrhosis (group A) or schistosomal periportal fibroses (group B) presenting within 24 h of the onset of the bleeding were enrolled in the study and followed for a period of 6 wk. Analysis of data was done by Microsoft Excel and comparison between groups was done by Statistical Package of Social Sciences version 20 to calculate means and find the levels of statistical differences and define the mortality rates, the P value of RESULTSA total of 94 patients were enrolled in the study. Thirty-two patients (34%) had liver cirrhosis (group A) and 62 (66%) patients had periportal fibrosis (group B). Mortality: The 6-wk and 5-d mortality were 53% and 16% respectively in group A compared to 10% and 0% in group B (P value P value P value P value P value P value P value CONCLUSIONThe 6-wk and 5-d mortality and rebleeding rate were significantly higher in patients with liver cirrhosis compared to patients with schistosomal periportal fibrosis.

Human thrombin for the treatment of gastric and ectopic varices

AIM:To evaluate the efficacy of human thrombin in the treatment of bleeding gastric and ectopic varices.METHODS:Retrospective observational study in a Tertiary Referral Centre.Between January 1999-October 2005,we identified 37 patients who were endoscopically treated with human thrombin injection therapy for bleeding gastric and ectopic varices.Patient details including age,gender and aetiology of liver disease/segmental portal hypertension were documented.The thrombin was obtained from the Scottish National Blood Transfusion Service and prepared to give a solution of 250 IU/mL which was injected via a standard injection needle.All patient case notes were reviewed and the total dose of thrombin given along with the number of endoscopy sessions was recorded.Initial haemostasis rates,rebleeding rates and mortality were catalogued along with the incidence of any immediate complications which could be attributable to the thrombin therapy.The duration of follow up was also listed.The study was conducted according to the United Kingdom research ethics guidelines.RESULTS:Thirty-seven patients were included.33 patients(89%) had thrombin(250 U/mL) for gastric varices,2(5.4%) for duodenal varices,1 for rectal varices and 1 for gastric and rectal varices.(1) Gastric varices,an average of 15.2 mL of thrombin was used per patient.Re-bleeding occurred in 4 patients(10.8%),managed in 2 by a transjugular intrahepatic portosystemic shunt(TIPSS)(one unsuccessfully who died) and in other 2 by a distal splenorenal shunt;(2) Duodenal varices(or type 2 isolated gastric varices),an average of 12.5 mL was used per patient over 2-3 endoscopy sessions.Re-bleeding occurred in one patient,which was treated by TIPSS;and(3) Rectal varices,an average of 18.3 mL was used per patient over 3 endoscopy sessions.No re-bleeding occurred in this group.CONCLUSION:Human thrombin is a safe,easy to use and effective therapeutic option to control haemorrhage from gastric and ectopic varices.

Non-selective beta-blockers in cirrhosis:Current concepts and controversies

Non-selective beta-blockers(NSBBs) have been at the forefront in the management of portal hypertension in liver cirrhosis for the last three decades, a trusty component in the armamentarium of the Hepatologist. The role of beta-blockers has been cemented for years in cardiac disease including angina, hypertension and in heart failure, however NSBBs with their non-selective effects on β1 and β2 receptors have led to them fondly being termed "the hepatologist's aspirin". NSBBs' role in reduction of portal pressure in the setting of primary and secondary prophylaxis for variceal haemorrhage has been well established. NSBBs include propranolol, nadolol and carvedilol- with the latter having been shown to be effective in patients who often fail to demonstrate a haemodynamic response to propranolol. Recent observational studies however have served for the Hepatology community to question the beneficial role of NSBBs in portal hypertension, especially in advanced cases with refractory ascites. The deleterious effect in patients with refractory ascites in a few studies led to a U-turn in clinical practice, with some in the Hepatology community withdrawing their usage in patients with advanced cirrhosis. This also led to the "window hypothesis" suggesting there may be only be a finite time frame when NSBBs have a beneficial effect in portal hypertension. The window hypothesis proposed the window for the benefits of NSBBs is closed in early portal hypertension, opening as portal hypertension progresses with it closing in advanced liver disease. The window was proposed to close in conditions such as refractory ascites or spontaneous bacterial peritonitis when patients may not necessarily mount a compensatory haemodynamic response when on NSBBs. Some centres however have continued the practice of NSBBs in advanced cirrhosis with published data challenging the scepticisms of other groups who stop NSBBs. Thus the debate, like the window hypothesis has opened, with more questions to be answered about NSBB's mechanism of action not only in reducing portal hypertension but also their effects on systemic haemodynamics and on the pro-inflammatory pathways often activated in cirrhosis especially in advanced disease. This article serves to review the role of NSBBs in the management of portal hypertension/cirrhosis and concentrate on current concepts and controversies in this field.

Recent advances in the management of variceal bleeding

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.