Bacterial infections in patients with acute hemorrhage due to portal hypertension--personal experience

Acute haemorrhage from the upper gastrointestinal tract is a frequent and serious complication which affects 20-60% patients with cirrhosis of the liver and portal hypertension. It is assumed that bacterial infections can be the direct cause of haemorrhage but accurate data on the influence of infection on the development and course of haemorrhage are lacking. Acute haemorrhage as a result of portal hypertension has a very high mortality, 30-50%, and an early relapse of haemorrhage occurs in as many as 40% of these patients. Most recent meta-analyses indicate that bacterial infection is an independent prognostic factor in failure of haemostasis and has a significant impact on the mortality of these patients. The authors examined for the presence of bacterial infection (blood, urine, throat, ascites) 25 patients with cirrhosis of the liver and acute haemorrhage as a result of portal hypertension and compared the results with a group of 25 patients with cirrhosis of the liver and portal hypertension without acute haemorrhage. According to the results in patients with acute haemorrhage due to portal hypertension there is a significantly higher incidence of bacterial infections than in patients with cirrhosis of the liver and portal hypertension without acute haemorrhage. The results confirm the necessity to administer antibiotic prophylaxis to cirrhotic patients with varicose bleeding, not only to patients with symptoms and evidence of infection but also in their absence. Antibiotic prophylaxis extends the survival period of these patients.     

Peripapillary duodenal varices as a rare cause of severe bleeding in a patient with no other signs of portal hypertension--successful endoscopic treatment with cyanoacrylate injection

Duodenal varices (DVs) are a rare cause of upper gastrointestinal bleeding and rather suspected in patients with portal hypertension. Bleeding DVs are difficult to manage and often fatal due to delayed diagnosis. We report on a 71-year-old patient with massive upper gastrointestinal haemorrhage, who did not show any clinical signs of portal hypertension; however, he had a history of duodenal segmental resection 8 years before. The source of bleeding could not be detected with different imaging methods such as angiography and computed tomography. Upper gastrointestinal endoscopy finally revealed DVs, which were located just adjacent to the papilla. After endoscopic injection therapy with n-butyl 2-cyanoacrylate the bleeding stopped immediately and the patient soon stabilised. Despite the peripapillar localisation no signs of pancreatitis or cholestasis occurred; during 10-month follow-up a marked regression of the varices without further signs of variceal bleeding was observed.     

What's new in portal hypertension?

Portal hypertension is defined as increased pressure in the portal venous system. The most common cause of portal hypertension is cirrhosis. In this setting, there is an increase in intrahepatic resistance leading to an increase in portal pressure. By increasing portal blood flow, splanchnic vasodilation further aggravates portal hypertension. New pathogenic pathways are being established which might result in new therapeutic strategies. The presence of varices at endoscopy and/or other abdominal portosystemic collaterals confirms the diagnosis of portal hypertension. The role of non‐invasive and imaging tests in the diagnosis and prognosis of portal hypertension has been clarified. Non‐selective beta‐blockers decrease both the risk of variceal haemorrhage and hepatic decompensation. Terlipressin, somatostatin or octreotide, in combination with early endoscopic therapy, are recommended for the treatment of acute variceal haemorrhage. Early Transjugular intrahepatic portosystemic shunt (TIPS) is effective as salvage therapy in acute variceal bleeding in selected patients and prevents rebleeding more effectively than endoscopic and medical therapy resulting in an increased survival.     

Transhepatic Embolisation of Gastro-oesophageal Varices in the Management of Variceal Haemorrhage

Summary The difficulty of controlling variceal haemorrhage has led to the recent development of methods designed to sclerose the bleeding vessels. This study describes the application of percutaneous transhepatic portal catheterization with emboiisation and sclerosis of varices in eight consecutive patients admitted with bleeding oesophago-gastric varices. Portal hypertension was documented and varices demonstrated in each case. Bleeding ceased rapidly in seven patients, two patients rebled 1–3 weeks after the procedure, and five patients were subsequently discharged from hospital. In no instance was death related to continued gastrointestinal haemorrhage. Initial experience with transhepatic embolisation of bleeding oesophago-gastric varices indicates that this technique is effective in controlling variceal haemorrhage.     

Overt gastrointestinal bleeding in haematologic neoplasms

BACKGROUND AND AIM: Patients with acute leukaemia suffer from various haemorrhages, most frequently due to thrombocytopenia. We could not reach any information regarding the frequency of gastrointestinal bleeding in acute leukaemia and decided to search this complication in patients with acute and chronic leukaemias and myeloproliferative disorders, retrospectively. PATIENTS AND METHODS: During a 6-year period, 291 patients with acute leukaemia, 52 patients with chronic leukaemia and 108 patients with myeloproliferative disorders had been followed. Thirty-two cases of overt gastrointestinal haemorrhage episodes (25 upper, 7 lower) were observed during the mentioned period. RESULTS: The frequency of bleeding episodes was 7.1% (32/451) in haematologic malignancies as a whole, 5.8% (17/291) for acute leukaemia, 1.9% (1/52) for chronic leukaemia and 13% (14/108) for myeloproliferative disorders. If the patients with myeloproliferative disorders in blastic phase were analysed separately, the ratio was 30% (6/20). Oesophagogastroduodenoscopy, which could be performed in 8 of 25 upper gastrointestinal haemorrhage episodes, revealed erosive gastritis in five patients and duodenal ulcers in three patients. Neutropenic enterocolitis was the underlying cause in all of the seven patients with lower gastrointestinal haemorhage. Five out of the seven patients had acute leukaemia. In 7 bleeding attacks, out of 32, the ultimate result was death. Generally, the haemorrhage was only a contributing cause of mortality. All of the mortality cases were patients with acute leukaemia. CONCLUSION: Especially, the patients with myeloproliferative disorders are prone to develop gastrointestinal haemorrhage. The manifestation is generally as upper gastrointestinal bleeding due to gastric erosions and duodenal ulcers. Lower gastrointestinal bleeding is frequently a problem of the patients with acute leukaemia. It is commonly a sign of neutropenic enterocolitis.     

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.     

Duplex sonography study in schistosomiasis portal hypertension: characterization of patients with and without a history of variceal bleeding

BACKGROUND: Presinusoidal portal hypertension with frequent episodes of upper gastrointestinal variceal bleeding are hallmarks of hepatosplenic Mansons schistosomiasis; a clinical form that affects about 5% of Brazilians who are infected by Schistosoma mansoni. AIMS: To evaluate duplex sonography findings in patients with hepatosplenic Mansons schistosomiasis with and without upper gastrointestinal variceal hemorrhage. METHODS: A cross-sectional study was performed whereby 27 consecutive patients with hepatosplenic Mansons schistosomiasis were divided into two groups: group I (six men and six women; mean age 48.7 years) with a past history of bleeding and group II (four men and eight women; mean age 44.7 years) without a past history of upper gastrointestinal bleeding, underwent duplex sonography examination. All patients underwent the same upper gastrointestinal endoscopy and laboratory examinations. Those with signs of mixed chronic liver disease or portal vein thrombosis (three cases) were excluded. RESULTS: Group I showed significantly higher mean portal vein flow velocity than group II (26.36 cm/s vs 17.15 cm/sec). Although, as a whole it was not significant in all forms of collateral vessels (83% vs 100%), there was a significantly higher frequency of splenorenal collateral circulation type in group II compared with group I (17% vs 67%). The congestion index of the portal vein was significantly lower in group I than in group II (0.057 cm vs 0.073 cm/sec). CONCLUSION: Our duplex sonography findings in hepatosplenic Mansons schistosomiasis support the idea that schistosomotic portal hypertension is strongly influenced by overflow status, and that collateral circulation seems to play an important role in hemodynamic behavior.     

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 de-cades with improved survival from an often-terminating event in recent past.     

Non-cirrhotic portal hypertension versus idiopathic portal hypertension

Portal hypertension occurs in a number of disorders other than cirrhosis and they are collectively called non-cirrhotic portal hypertension (NCPH). The common causes of NCPH include idiopathic portal hypertension (IPH), non-cirrhotic portal fibrosis (NCPF) and extrahepatic portal venous thrombosis (EHPVT). Other causes include schistosomiasis, hepatic venous outflow tract obstruction, veno-occlusive disease and congenital hepatic fibrosis. Patients with IPH and EHPVT present with upper gastrointestinal bleeding, splenomegaly, ascites after gastrointestinal bleeding, features of hypersplenism, growth retardation and jaundice due to portal biliopathy. The diagnosis is usually made by abdominal ultrasound, upper gastrointestinal endoscopy, normal liver function tests and normal liver histology. Variceal bleeding in NCPH has lower mortality as compared with cirrhosis because of better liver functions in NCPH. Treatment for NCPH includes primary prophylaxis for variceal bleeding and prevention of repeat bleeding using drugs like beta-blockers, endoscopic sclerotherapy and endoscopic band ligation of varices. In patients with uncontrolled variceal bleeding or symptomatic hypersplenism, porto-systemic shunt surgery or splenectomy are required.     

The use of hemospray in portal hypertensive bleeding; a case series

Hemospray is a haemostatic agent licensed for endoscopic haemostasis of non-variceal upper gastrointestinal bleeding (NVUGIB) in Europe and Canada. Hemospray has been shown to be safe and effective in achieving haemostasis in bleeding peptic ulcers in a prospective clinical study and several further case series have described the use of hemospray in other non-variceal causes of gastrointestinal bleeding. Portal hypertensive gastropathy and colopathy are common in patients with portal hypertension. As hemospray is an easy to apply, non-contact method, which can cover large areas of mucosa, it may be of benefit in acute non-variceal portal hypertensive bleeding. We present data from the first four consecutive patients presenting to our institution with acute haemorrhage secondary to non-variceal diffuse portal hypertensive bleeding treated with hemospray.     

Transjugular intrahepatic portasystemic stent shunting for control of acute and recurrent upper gastrointestinal haemorrhage related to portal hypertension.

The insertion of a transjugular intrahepatic portasystemic stent shunt (TIPSS) was evaluated in 22 patients with recurrent upper gastrointestinal haemorrhage related to portal hypertension (bleeding from oesophageal varices 10, gastric varices six, portal hypertensive gastropathy six). TIPSS was successfully performed electively in 15 patients and as an emergency in three patients. Twelve patients have had no further admissions with bleeding after TIPSS. Single episodes of bleeding were noted in six patients after TIPSS associated with shunt thrombosis (two), intimal hyperplasia within the shunt (two), and shunt migration (one). Another patient presented with reaccumulated ascites suggesting poor shunt function but died from massive variceal haemorrhage before further assessment could be performed. There was one death related to the procedure. Two patients developed encephalopathy after TIPSS, in one patient this was controlled by the insertion of a smaller diameter stent within the existing TIPSS. Several complications arose in earlier patients that have not recurred after modification of the initial technique. TIPSS can be life saving and is effective in controlling variceal haemorrhage and rebleeding from oesophageal or gastric varices and portal hypertensive gastropathy. Larger and longer term studies are required, however, to define the role of TIPSS in the overall management of such patients.     

Improving prognosis following a first variceal haemorrhage over four decades

BACKGROUND: Variceal bleeding is a frequent cause of death in patients with cirrhosis and portal hypertension. Over the past 40 years a number of new techniques have been introduced to control active variceal haemorrhage. Many randomised controlled trials were performed to evaluate these new therapies. While most have demonstrated efficacy in controlling haemorrhage few showed improved survival. AIM: The aim of this study was to investigate whether the prognosis for cirrhotic patients following a first variceal haemorrhage has improved over the past four decades. PATIENTS AND METHODS: A total of 1475 patients included in the control or untreated arms of randomised controlled prophylactic trials for the primary prevention of variceal haemorrhage between 1960 and 2000. Twenty eight eligible randomised controlled studies were included. Over the 40 year period of observation there was a reduction in bleeding related mortality over time from approximately 65% to approximately 40% (p=0.024). CONCLUSION: This study suggests that there has been a significant reduction in bleeding related mortality in patients with cirrhosis and portal hypertension over the past 40 years.     

Management of upper gastrointestinal haemorrhage

Abstract Endoscopic therapy is the first treatment modality in the management algorithm of upper gastrointestinal haemorrhage. In treating bleeding peptic ulcers, diluted epinephrine is first injected followed by targeted treatment to the vessel. Combination therapy adding thermocoagulation or thrombin/fibrin products has been shown to further improve the rate of haemostasis. There is also some evidence to suggest that adjuvant use of optimal acid suppression using high-dose proton pump inhibitors can reduce recurrent bleeding after initial endoscopic control. In treating acute variceal haemorrhage, early administration of vasoactive agents facilitates endoscopic treatment. These drugs should be continued during and after endoscopic therapy to prevent recurrent in-hospital bleeding. Firm evidence exists to date that band ligation is the endoscopic treatment of choice in the acute control of bleeding varices and their secondary prophylaxis against recurrent bleeding. The role of band ligation as primary prophylaxis for first bleeding remains controversial. Transjugular intrahepatic porto-systemic shunts are used as a rescue procedure when endoscopic treatment fails. In selected patients with recurrent variceal haemorrhage and good hepatic reserves, surgical shunts may be indicated.     

Fibreoptic endoscopy and the use of the Sengstaken tube in acute gastrointestinal haemorrhage in patients with portal hypertension and varices.

The value of emergency upper gastrointestinal fibre-endoscopy, followed where required by the use of a modified Sengstaken tube, was studied during 84 episodes of acute bleeding in 75 patients who had evidence of portal hypertension with varices. The portal hypertension was due to alcoholic cirrhosis in 80% and to cryptogenic cirrhosis in 9% of the patients. By definition, varices were present in all patients, but in only 66% of episodes were the varices the cause of the bleed. The correct diagnosis of the source of bleeding was made at endoscopy in 89%. A Boyce modification of the Sengstaken-Blakemore tube was passed in 73% of the episodes of variceal bleeding. It effectively stopped the bleeding primarily in 85% of patients but was successful as a final definitive measure only in 46%. Furthermore, only 40% of the patients in whom the tube was passed, survived. Mortality rate could be related to the severity of the bleed and to hepatocellular dysfunction. Survival increased from 23% in those patients with jaundice, ascites, and encephalopathy on admission to 92% in those without these manifestations. The in-hospital survival rate was 52% in patients bleeding from varices and 64% in those bleeding from other causes, with an overall survival rate of 56%, indicating the poor prognosis in cirrhotic patients with gastrointestinal bleeding, irrespective of the cause.     

Upper gastrointestinal bleeding in patients with portal hypertension: a reappraisal

The current medical literature states that upper gastrointestinal bleeding in patients with cirrhosis and portal hypertension originates from a variety of sources. Although variceal bleeding has been recognized as the principal source, acute erosive gastritis and peptic ulcer are said to be the bleeding site in a large percentage of cases. In 140 consecutive patients with endoscopically documented esophageal varices who came to our service with upper gastrointestinal hemorrhage, varices were the source of bleeding in approximately 90%, regardless of whether the underlying liver disease was due to alcoholism or not. We conclude that: 1) patients with varices almost always bleed from varices, and 2) the incidence of erosive gastritis and peptic ulcer as a cause of bleeding in this group has been overemphasized.     

Non-cirrhotic portal fibrosis: current concepts and management

Non-cirrhotic portal hypertension (NCPH) comprises diseases having an increase in portal pressure (PP) due to intraheptic or prehepatic lesions, in the absence of cirrhosis. The lesions are generally vascular, either in the portal vein, its branches or in the perisinusoidal area. Because the wedged hepatic venous pressure is near normal, measurement of intravariceal or intrasplenic pressure is needed to assess PP. The majority of diseases included in the category of NCPH are well-characterized disease entities where portal hypertension (PHT) is a late manifestation and, hence, these are not discussed. Two diseases that present only with features of PHT and are common in developing countries are non-cirrhotic portal fibrosis (NCPF) and extrahepatic portal vein obstruction (EHPVO). Non-cirrhotic portal fibrosis is a syndrome of obscure etiology, characterized by 'obliterative portovenopathy' leading to PHT, massive splenomegaly and well-tolerated episodes of variceal bleeding in young adults from low socioeconomic backgrounds, having near normal hepatic functions. In some parts of the world, NCPF is called idiopathic portal hypertension (IPH) or 'hepatoportal sclerosis'. Because 85-95% of patients with NCPF and EHPVO present with variceal bleeding, treatment involves management with endoscopic sclerotherapy (EST) or variceal ligation (EVL). These therapies are effective in approximately 90-95% of patients. Gastric varices are another common cause of upper gastrointestinal bleeding in these patients and these can be managed with cyanoacrylate glue injection or surgery. Other indications for surgery include failure of EST/EVL, and symptomatic hypersplenism. The prognosis of patients with NCPF is good and 5 years survival in patients in whom variceal bleeding can be controlled has been reported to be approximately 95-100%.     

Antibiotic prophylaxis in patients with acute hemorrhage due to portal hypertension--personal experience

Acute bleeding from upper part of gastrointestinal tract is a frequent and serious complication affecting 20 to 60% of patients with liver cirrhosis and portal hypertension. It is associated with a high death rate of 30 to 50% and a frequent relapse of bleeding occurs in up to 40% of these patients. The most recent meta-analyses have shown that bacterial infection is an independent factor in the failure of blood hemostasis and significantly influenced mortality in these patients. The authors investigated 25 patients with acute bleeding from the upper part of gastrointestinal tract due to portal hypertension in patients with liver cirrhosis. Irrespective of the proved bacterial infection the patients were given antibiotic prophylaxis. In 13 patients the authors administered norfloxacin orally and 12 patients were treated intravenously with ampicilin/sulbactam. The prophylaxis of the bleeding cirrhotic patients by norfloxacin (orally) resulted in a statistically significant prevention of early relapse as compared with the therapy by ampicilin/sulbactam (intravenously). The death rate reached 40% in spite of the antibiotic prophylaxis. There was no significant difference in the death rate between the two groups with different treatments.     

Results of the management of upper gastrointestinal bleeding from gastroesophageal varices.

INTRODUCTION: The management of upper gastrointestinal bleeding caused by rupture of gastric and/or esophageal varices in patients with liver cirrhosis must focus on the initial control of the haemorrhage avoiding further worsening of an already poor liver function and the prevention of early relapsing bleeding. Therapeutic options include endoscopic, pharmacological and surgical methods. MATERIAL AND METHODS: Prospective study of the results obtained after the follow-up of 90 bleeding episodes in a total of 54 patients, 35 men and 19 women, with a mean age of 58 years (range 32-77), to which a therapeutic protocol for acute bleeding secondary to portal hypertension was applied over a 22-months period. Patient classification according to Child-Pugh upon admission was 57% Child A, 34% Child B and 9% Child C. RESULTS: Mean hospital length of stay was 9 days (2-50). Of the 90 bleeding episodes, 15 were early relapsing bleeding episodes (16.7%). Twelve patients died (mortality rate of 22.2% by patients and 13.4% by bleeding episodes). Twelve emergency surgical procedures were performed because of the persistence of haemorrhage. Forty one per cent of patients were readmitted because of relapsing bleeding at least once during the follow-up period. CONCLUSIONS: Management of upper gastrointestinal bleeding due to gastroesophageal varices in patients with liver cirrhosis requires a combined therapy in order to attain maximum effectiveness in acute haemorrhagic episodes and to address all potential later consequences. Such therapy should be provided in a hospital fully equipped and with specialists in this pathology. Based on our experience, emergency surgery as rescue treatment for persistent or short-term relapsing bleeding should be restricted to patients with good hepatic function because of its high morbidity and mortality.     

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.     

经颈静脉肝内门体分流术在肝硬化静脉曲张出血防治中的地位

静脉曲张出血是肝硬化门静脉高压常见的致死性并发症,大约50%的肝硬化患者在诊断为肝硬化时既已合并静脉曲张。自从1988年经颈静脉肝内门体分流术(TIPS)首次应用于临床以来,大量的临床研究不断的更新与完善了TIPS的相关知识。本文主要对TIPS在肝硬化门静脉高压静脉曲张出血的防治中的地位作一综述,包括TIPS在肝硬化门脉高压静脉曲张出血的初级预防、急性静脉曲张出血的治疗以及肝硬化静脉曲张再出血的预防中的应用。TIPS是肝硬化门静脉高压静脉曲张的有效疗法,随着技术的不断进步,将有越来越多的患者成为TIPS的适应证,TIPS在肝硬化门脉高压静脉曲张出血的防治中将发挥越来越重要的作用。