Development of Gastroesophageal Varices and Risk of Variceal Bleeding in Patients With Cirrhosis

Abstract: We studied the relationships between portal pressure measured using the portal venous pressure gradient, the development of gastroesophageal varices, and the risk of variceal bleeding in 56 patients with cirrhosis. Portal pressure was higher in patients with varices than in those without (P>0.01), and 11 mmHg was the lowest portal pressure measured in the patients with varices. The size of the varices was not associated with the portal pressure. There was no difference in the value of portal pressure measurements for the patients with variceal bleeding and those without and there was no linear-relationship between the degree of portal hypertension and the rate of variceal bleeding. 12 mmHg was the lowest portal pressure measured in the patients with variceal bleeding. The size of the varices was related to the rate of variceal bleeding (P>0.05). We conclude that (a) a portal pressure of 11 mmHg is necessary for the formation of varices, (b) 12 mmHg of portal pressure is necessary for variceal bleeding to occur but the degree of portal hypertension has no predictive value for the risk of variceal bleeding, and (c) the size of the varices does not depend on the degree of portal hypertension but is associated with the risk of variceal bleeding.     

Risk factors for haemorrhage from oesophageal varices and acute gastric erosions

Rupture, versus erosion, is the most likely cause of variceal bleeding. The risk of rupture appears to be enhanced in large varices and varices with reddish discoloration. Incompetent perforating veins connecting varices to deeper venous systems may also be important in the pathogenesis of this event. Perhaps one-third of patients with large varices will bleed from them over a period of one to two years. Portal hypertension cannot be used to predict the future risk of bleeding among groups of patients. Nevertheless, it is possible that increases or decreases in portal pressure in individual patients may alter their bleeding risk. We and others have observed portal pressure as low as 10 mmHg in patients with clear-cut, recurrent variceal bleeding. Portal hypertension probably predisposes to gastric mucosal injury by enhancing, by an undefined mechanism, back-diffusion of acid. Consequently, haemorrhagic gastritis is more common in patients with portal hypertension than those without. Whether haemorrhagic gastritis is a more severe lesion in patients with portal hypertension is unclear.     

The management of portal hypertension: rational basis, available treatments and future options

Variceal bleeding is the last step in a chain of events initiated by an increase in portal pressure, followed by the development and progressive dilation of varices until these finally rupture and bleed. This sequence of events might be prevented - and reversed - by achieving a sufficient decrease in portal pressure. A different approach is the use of local endoscopic treatments at the varices. This article reviews the rationale for the management of patients with cirrhosis and portal hypertension, the current recommendations for the prevention and treatment of variceal bleeding, and outlines the unsolved issues and the perspectives for the future opened by new research developments.     

Beneficial long term effect of a phosphodiesterase-5-inhibitor in cirrhotic portal hypertension: A case report with 8 years follow-up

Non-selective beta-blockers are the mainstay of medical therapy for portal hypertension in liver cirrhosis. Inhibitors of phosphodiesterase-5(PDE-5-inhibitors) reduce portal pressure in the acute setting by 10% which may suggest a long-term beneficial effect. Currently, there is no available data on long-term treatment of portal hypertension with PDE-5-inhibitors. This case of a patient with liver cirrhosis secondary to autoimmune liver disease with episodes of bleeding from esophageal varices is the first documented case in which a treatment with a PDE-5-inhibitor for eight years was monitored. In the acute setting, the PDE-5-inhibitor Vardenafil lowered portal pressure by 13%. The portal blood flow increased by 28% based onDoppler sonography and by 16% using MRI technique. As maintenance medication the PDE-5-inhibitor Tadalafil was used for eight consecutive years with comparable effects on portal pressure and portal blood flow. There were no recurrence of bleeding and no formation of new varices. Influencing the NO-pathway by the use of PDE-5 inhibitors may have long-term beneficial effects in compensated cirrhosis.     

Rectal varices in extrahepatic portal hypertension

Abstract Rectal varices, as distinct from haemorrhoids, occur due to high pressure in the inferior mesenteric venous system in patients with portal hypertension. The exact prevalence of rectal varices in extrahepatic portal hypertension is unknown. To determine this, 116 patients with extrahepatic portal hypertension were studied for the presence of rectal varices. These lesions were found in 103 (88.8%) patients. Bleeding from rectal varices occurred in 14.6% of patients. Massive bleeding requiring hospitalization and blood transfusion was not encountered. It is concluded that rectal varices are common in extrahepatic portal hypertension. Bleeding from them is uncommon, and often mild and self-limiting. The available literature is reviewed and the importance of recognizing the condition stressed.     

Gastric Varices: Profile, Classification, and Management

Development of gastric varices is an important manifestation of portal hypertension. In segmental portal hypertension, gastric varices originate from short gastric and gastroepiploic veins. In generalized portal hypertension, intrinsic veins at cardia participate in the formation of gastric varices. Endoscopy and/or splenoportovenography and a high index of suspicion are required for the diagnosis of gastric varices. The incidence of gastric varices in patients with portal hypertension has been variably reported (2-70%), probably due to difficulties in diagnosis. In a small proportion of patients with gastric varices, chronic portal-systemic encephalopathy or significant variceal bleeding develops. Gastric varices can be classified, depending on their anatomical location, into gastroesophageal varices (a continuation of esophageal varices) or "isolated" gastric varices (fundal or ectopic varices). This distinction is necessary for management. Whereas surgery is recommended for bleeding fundal varices, in acute bleeding from gastroesophageal varices, sclerotherapy could be attempted successfully. In more than a quarter of patients, gastric varices disappear after obliteration of esophageal varices. Prophylactic sclerotherapy of gastric varices is not recommended.     

Indications for portal pressure measurement in chronic liver disease

Abstract Portal hypertension leads to development of serious complications such as esophageal varices, ascites, renal and cardiovascular dysfunction. The importance of the degree of portal hypertension has been substantiated within recent years. Measurement of the portal pressure is simple and safe and the hepatic venous pressure gradient (HVPG) independently predicts survival and development of complications such as ascites, HCC and bleeding from esophageal varices. Moreover, measurements of HVPG can be used to guide pharmacotherapy for primary and secondary prophylaxis for variceal bleeding. Assessment of HVPG should therefore be considered as a part of the general characterization of patients with portal hypertension in departments assessing and treating this condition.     

3 Natural history. Clinical-haemodynamic correlations. Prediction of the risk of bleeding

Promoting the development of oesophageal varices and ascites, portal hypertension dominates the clinical course of cirrhosis. Varices appear in patients with portal pressure gradient above 10 mmHg and enlarge in 10–20% within 1–2 years of their detection. Bleeding occurs in patients with portal pressure gradient above 12 mmHg when the wall tension causes the rupture of varices, with an incidence of about 10% per year. Indicators of bleeding risk are portal pressure gradient, variceal pressure, large varices and liver dysfunction. Mortality per bleeding episode is 30–50%. Among survivors 60% will rebleed and 30% will die in the following year. The risk of rebleeding decreases in patients with spontaneous or treatment induced reduction of portal pressure gradinent or variceal pressure. Ascites develops in almost all patients along the course of the disease. Median survival after its appearance is less than 2 years. Less than 5% of cirrhotic patients die without ascites or without a previous bleeding. Thus portal hypertension is a major determinant of survival in cirrhosis.     

Variceal pressure is a strong predictor of variceal haemorrhage in patients with cirrhosis as well as in patients with non-cirrhotic portal hypertension

BACKGROUND: Variceal pressure is a strong predictor for a first variceal bleed in patients with cirrhosis. AIMS: To evaluate whether variceal pressure is also a determinant of the risk of a first variceal bleed in patients with non-cirrhotic portal hypertension. METHODS: Variceal pressure was measured non-invasively in 25 patients with non-cirrhotic portal hypertension and large varices while receiving a stable therapeutic regimen. Factors predictive of bleeding were compared with those observed in 87 cirrhotics. RESULTS: The one year incidence of variceal bleeding was 32% (n=28) for the cirrhotic and 20% (n=5) for the non-cirrhotic patients. There was no difference in factors predicting the risk of bleeding between the groups, except for variceal pressure. For the same level of variceal pressure, the risk of variceal bleeding was lower in patients with non-cirrhotic portal hypertension. Multiple logistic regression analysis revealed the following variables as having a significant predictive power: variceal pressure (p=0.0001), red spots (p=0.004), and the time interval between the first observation of the varices and the moment of variceal pressure measurement (p=0. 0046). For the non-cirrhotics the risk of bleeding increased with higher Child-Pugh score (p=0.0024); this was not the case for the cirrhotic patients (p=0.9521). CONCLUSION: Variceal pressure is a major predictor of variceal bleeding in patients with cirrhosis as well as in patients with non-cirrhotic portal hypertension. The risk of bleeding in non-cirrhotics is less than in cirrhotics for the same level of variceal pressure. In patients with non-cirrhotic portal hypertension the risk of variceal bleeding increases more with advancing disease.     

The effects of transjugular intrahepatic portosystemic shunt on portal hypertensive gastropathy

In addition to variceal bleeding, haematemesis may occur due to haemorrhagic gastritis in patients with portal hypertension. This has been known as portal hypertensive gastropathy (PHG). We have evaluated the effects of the transjugular intrahepatic portosystemic shunt (TIPS) on portal venous pressure (PVP) and endoscopic gastric mucosal changes observed in patients with portal hypertension. We performed TIPS in 12 patients with complications due to portal hypertension as follows: variceal bleeding in nine patients (bleeding from oesophageal varices in seven and gastric varices in two), refractory ascites in three and haemorrhage from severe PHG in one. Endoscopic examinations were performed before and after TIPS for all patients. Changes of PVP and gastric mucosal findings on endoscopy were analysed. Before TIPS, PHG was seen in 10 patients. Portal venous pressure decreased from an average of 25.1 ± 8.8 to 17.1 ± 6.2 mmHg after TIPS ( P < 0.005). On endoscopy, PHG improved in nine of 10 patients. Oesophagogastric varices improved in eight of 11 patients. In one patient with massive haematemesis, haemorrhage from severe PHG completely stopped after TIPS. Because TIPS effectively reduced PVP, this procedure appeared to be effective for the treatment of uncontrollable PHG.     

门脉高压性小肠病

小肠改变是门脉高压门静脉高压症是一组由门静脉压力持续增高引起的症候群,最常见表现是消化道出血,特别是食管胃静脉曲张破裂出血.随着小肠检查手段的发展,特别是胶囊内镜和双气囊小肠镜,发现门脉高压下小肠发生了病变,被定义为门脉高压性小肠病(PHE),这种改变也是消化道出血的重要原因.消化道出血的患者,胃或食管没有静脉曲张情况...     

Evaluation of esophageal varices in liver disease by splenic-pulp manometry,splenoportography, and esophagogastroscopy

Summary and Conclusion Esophagogastroscopy, splenic-pulp manometry, and splenoportography were combined in a prospective study of 60 patients with documented liver disease and suspected portal hypertension. All three procedures were performed on each of the patients within a 6-day period. Twenty patients were actively bleeding at the time of endoscopic examination.Esophagogastroscopy demonstrated varices in 90% of the patients studied. Splenoportography, however, demonstrated collateral circulation in only 50% of the patients with endoscopically demonstrated varices. In no instance did splenoportography demonstrate collateral circulation not previously seen on endoscopy. Splenoportography failed to demonstrate collateral circulation in all patients whose splenic-pulp pressure was less than 270 mm. water.In 20 patients with upper gastrointestinal bleeding, the height of the splenic-pulp pressure was a poor index of the site of bleeding. Eight patients with portal hypertension and esophageal varices were found to be bleeding from nonvariceal sites. Conversely, 5 patients with active bleeding from endoscopically demonstrated varices had no collateral circulation revealed by splenoportography.It is evident from this study that splenic-pulp manometry, splenoportography, and esophagogastroscopy will frequently yield divergent results in the evaluation of portal hypertension and portosystemic collateral circulation in patients with liver disease. While splenoportography may be useful in determining the patency of the portal vein and demonstrating large spontaneous or surgical portosystemic shunts, esophagogastroscopy is a better method for detecting esophageal varices and determining whether they are bleeding. The height of the splenic-pulp pressure is of little value in indicating the site of upper gastrointestinal bleeding.Supported in part by Graduate Training Grant TI-AM-5237 and Clinical Research Center Grant AM-05576-02 from the National Institute of Arthritis and Metabolic Diseases, N.I.H., U. S. Public Health Service, and Contract U 1373 of the Health Research Council of the City of New York.     

Indications for portal pressure measurement in chronic liver disease

Abstract

Portal hypertension leads to development of serious complications such as esophageal varices, ascites, renal and cardiovascular dysfunction. The importance of the degree of portal hypertension has been substantiated within recent years. Measurement of the portal pressure is simple and safe and the hepatic venous pressure gradient (HVPG) independently predicts survival and development of complications such as ascites, HCC and bleeding from esophageal varices. Moreover, measurements of HVPG can be used to guide pharmacotherapy for primary and secondary prophylaxis for variceal bleeding. Assessment of HVPG should therefore be considered as a part of the general characterization of patients with portal hypertension in departments assessing and treating this condition.     

Arterioportal Fistula: A Role for Pre-TIPSS Arteriography and Hepatic Venous Pressure Measurements

A 70-yr-old male presented with massive upper gastrointestinal bleeding secondary to esophageal varices. Because the bleeding was not controlled by sclerotherapy or vasopressin and nitroglycerin, the patient was evaluated for a transjugular intrahepatic portosystemic shunt. Preprocedure arteriography was performed because the etiology of the portal hypertension was uncertain. The arteriogram revealed a hepatic artery to portal vein fistula. Hepatic venous pressure measurements documented an elevated hepatic venous pressure gradient, which diminished dramatically upon embolization of the fistula. Rebleeding from the varices was associated with reestablishment of the fistula via collaterals and elevation of the hepatic venous pressure gradient. The case is presented to establish a role for arteriography prior to transjugular intrahepatic portosystemic shunting, especially in patients with unexplained portal hypertension, and to establish the potential value of hepatic venous pressure measurements in the treatment of arterioportal fistulas.     

Long-term follow-up study of adult patients with non-cirrhotic obstruction of the portal system: comparison with cirrhotic patients.

Thirty-two patients with non-cirrhotic portal system obstruction and oesophageal varices of non-malignant etiology were recruited over 13 years. Diagnosis was based on the presence of oesophageal varices at endoscopy, minor alterations in liver function tests and liver histology, a low hepatic venous pressure gradient, and pertinent angiographic patterns. Twenty-three had portal vein thrombosis, nine had splenic vein thrombosis. Twenty-one had idiopathic portal vein obstruction, 11 had secondary obstruction. The outcome was compared with a group of 32 patients with cirrhosis and portal hypertension, matched for age, Child-Pugh class, previous history of gastrointestinal bleeding, and size of oesophageal varices. Patients with non-cirrhotic obstruction of the portal system were followed for up to 171 months (mean 94 months). During follow-up ten patients had gastrointestinal bleeding, and eight died (five of gastrointestinal bleeding). After 6 years of follow-up, the cumulative risk of gastrointestinal bleeding was 24%, the cumulative risk of death was 17%, and the cumulative risk of death from gastrointestinal bleeding was 14%. Cumulative probability of death by any cause and the probability of gastrointestinal bleeding were significantly lower in patients with non-cirrhotic obstruction of the portal system than in patients with cirrhosis comparable for liver function and portal hypertension (p = 0.04 for both). The cumulative probability of death by gastrointestinal bleeding was not significantly different. In conclusion, the prognosis for non-cirrhotic obstruction of the portal system is significantly better than for patients with cirrhosis with comparable levels of liver function impairment and severity of portal hypertension.     

Chronic lymphocytic leukemia with portal hypertension and without liver involvement: a case report underlining the roles of increased spleno-portal blood flow and "protective" sinusoidal vasoconstriction

We report the case of a 72-year-old woman with well-controlled chronic lymphocytic leukemia (CLL) and splenomegaly who developed portal hypertension with bleeding oesophageal varices in the absence of liver fibrosis or regenerative nodular hyperplasia at surgical wedge liver biopsy. The hepatic venous pressure gradient (HVPG) was elevated and splenectomy resulted in both its normalisation and the regression of oesophageal varices. This case shows the potential for an increased spleno-poral flow to generate severe portal hypertension likely through a "protective" sinusoidal vasoconstriction.     

Percutaneous transarterial embolization of extrahepatic arteroportal fistula

INTRODUCTION Extrahepatic arteroportal fistula is a rare disorderof hepatic vasculature characterized by anomalous communication between arteries and portal vein system most commonly caused by abdominal trauma, and iatrogenic damage induced by procedures …     

Varizenblutung

Esophageal variceal bleeding remains the most feared complication of portal hypertension and is associated with a significant mortality; thus, endoscopic screening of these patients is recommended. To date, neither medical nor interventional therapy can prevent the development of varices. However, the risk of variceal bleeding can be reduced using nonselective beta-blockers. Endoscopic prophylaxis is only recommended for patients with large varices that do not tolerate sufficient beta-blocker therapy. Endoscopic variceal ligation in combination with antibiotic prophylaxis as well as vasoactive agents, such as terlipressin, are the treatment of choice in acute variceal hemorrhage. If these measures fail to stop variceal bleeding, alternatives that include local compression of varices using special self-expanding stents or by reducing portal venous pressure with transjugular portosystemic shunts should be evaluated. Secondary prophylaxis consists of endoscopic variceal ligation and medical reduction of portal venous pressure.     

Contrast-Enhanced Three-Dimensional Magnetic Resonance Angiography for Visualization of Ectopic Varices

We report the case of a 62-year-old male with portal hypertension and recurrent bleeding refractory to surgical intervention from varices in a sigmoid stoma. Although stomal varices were detected neither by physical examination, stomal endoscopy, nor duplex sonography, contrast-enhanced three-dimensional magnetic resonance angiography of the portal vein and its collateral branches demonstrated their presence. Surgical revisions of the stoma failed to prevent bleeding, but implantation of a transjugular intrahepatic shunt successfully prevented recurrent hemorrhage. This case indicates that contrast-enhanced, three-dimensional magnetic resonance angiography is useful to detect this rare complication of portal hypertension and helps to tailor adequate treatment in patients with recurrent bleeding from stomal varices.     

Longterm outcome after injection sclerotherapy for oesophageal varices in children with extrahepatic portal hypertension.

A consecutive series of 36 children with bleeding from oesophageal varices secondary to extrahepatic portal hypertension was successfully treated by endoscopic injection sclerotherapy and followed up over a mean period of 8.7 years after variceal obliteration. There were no deaths from portal hypertension or its treatment and morbidity related to oesophageal sclerotherapy was minimal. Endoscopic injection sclerotherapy alone proved safe and effective in controlling variceal bleeding from portal hypertension in over 80% of the children. Recurrent variceal bleeding developed in 10 (31%) patients but half of these were effectively treated by further sclerotherapy. Gastric variceal bleeding unresponsive to sclerotherapy necessitated successful portosystemic shunt surgery in four (13%) patients. Two children required splenectomy for painful splenomegaly. In most children injection sclerotherapy is the best treatment for the primary management of bleeding oesophageal varices, reserving portosystemic shunting or other surgical procedures for those with bleeding from gastrointestinal varices.