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1.  Management of Variceal Hemorrhage in Children with Extrahepatic Portal Venous Obstruction-Shunt Surgery Versus Endoscopic Sclerotherapy 
The Indian Journal of Surgery  2011;73(6):409-413.
Extrahepatic portal venous obstruction (EHPVO) is a common cause of portal hypertention in children. Esophageal variceal hemorrhage is a major cause of morbidity and mortality in these patients. For many decades, portal systemic shunts were considered as the most effective treatment of variceal hemorrhage. Endoscopic injection sclerotherapy (EIS) was first introduced for emergency management of bleeding varices and subsequently as definitive treatment to prevent recurrent hemorrhage. The purpose of the study was to compare the safety and efficacy of shunt surgery and endoscopic sclerotherapy for patients with proven esophageal variceal bleeding due to EHPVO. The study was a prospective randomized study of 61 children with bleeding esophageal varices due to EHPVO carried out jointly by the department of General Surgery and Gastroenterology at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, between March 2001 and September 2003. Thirty patients received surgery and other 31 patients received EIS. Overall incidence of rebleeding was 22.6% in sclerotherapy group and 3.3% in shunt surgery group. Treatment failure occurred in 19.4% patients in sclerotherapy group and 6.7% in shunt surgery group. The rebleeding rate of sclerotherapy is significantly higher than that of shunt surgery. However, the therapy failure rate of sclerotherapy is not significantly different from that of shunt surgery.
doi:10.1007/s12262-011-0345-z
PMCID: PMC3236262  PMID: 23204696
Variceal bleeding; Endoscopic sclerotherapy; Shunt surgery; Rebleeding
2.  Variceal Band Ligation in the Prevention of Variceal Bleeding: A Multicenter Trial 
Background/Aim:
Variceal bleeding is a life-threatening complication of portal hypertension with a high probability of recurrence. Treatment to prevent first bleeding or rebleeding is mandatory. The study has been aimed at investigating the effectiveness of endoscopic band ligation in preventing upper gastrointestinal bleeding in patients with portal hypertension and to establish the clinical outcome of patients.
Patients and Methods:
We analyzed in a multicenter trial, the efficacy and side effects of endoscopic band ligation for the primary and secondary prophylaxis of esophageal variceal bleeding. We assigned 603 patients with portal hypertension who were hospitalized to receive treatment with endoscopic ligation. Sessions of ligation were repeated every two to three weeks until the varices were eradicated. The primary end point was recurrent bleeding.
Results:
The median follow-up period was 32 months. A total of 126 patients had recurrent bleeding. All episodes were related to portal hypertension and 79 to recurrent variceal bleeding. There were major complications in 51 patients (30 had bleeding esophageal ulcers). Seventy-eight patients died, 26 deaths were related to variceal bleeding and 1 to bleeding esophageal ulcers.
Conclusions:
A great improvement in the prevention of variceal bleeding has emerged over the last years. However, further therapeutic options that combine higher efficacy, better tolerance and fewer side effects are needed.
doi:10.4103/1319-3767.77238
PMCID: PMC3099054  PMID: 21372346
Endoscopic band ligation; esophageal varices; portal hypertension
3.  Portal hypertension and gastrointestinal bleeding: Diagnosis, prevention and management 
Bleeding from esophageal varices is a life threatening complication of portal hypertension. Primary prevention of bleeding in patients at risk for a first bleeding episode is therefore a major goal. Medical prophylaxis consists of non-selective beta-blockers like propranolol or carvedilol. Variceal endoscopic band ligation is equally effective but procedure related morbidity is a drawback of the method. Therapy of acute bleeding is based on three strategies: vasopressor drugs like terlipressin, antibiotics and endoscopic therapy. In refractory bleeding, self-expandable stents offer an option for bridging to definite treatments like transjugular intrahepatic portosystemic shunt (TIPS). Treatment of bleeding from gastric varices depends on vasopressor drugs and on injection of varices with cyanoacrylate. Strategies for primary or secondary prevention are based on non-selective beta-blockers but data from large clinical trials is lacking. Therapy of refractory bleeding relies on shunt-procedures like TIPS. Bleeding from ectopic varices, portal hypertensive gastropathy and gastric antral vascular ectasia-syndrome is less common. Possible medical and endoscopic treatment options are discussed.
doi:10.3748/wjg.v19.i31.5035
PMCID: PMC3746375  PMID: 23964137
Portal hypertension; Esophageal varices; Gastric varices; Portal hypertensive gastropathy; Gastric antral vascular ectasia-syndrome; Variceal bleeding; Endoscopy; Band ligation; Beta-blocker
4.  Longterm outcome after injection sclerotherapy for oesophageal varices in children with extrahepatic portal hypertension. 
Gut  1994;35(2):257-259.
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.
PMCID: PMC1374504  PMID: 8307479
5.  Prevention and Management of Gastroesophageal Varices in Cirrhosis 
Variceal hemorrhage is one of the major complications of liver cirrhosis associated with significant mortality and morbidity. Its management has evolved over the past decade and has substantially reduced the rate of first and recurrent bleeding while decreasing mortality. In general, treatment of esophageal varices can be divided into three categories: primary prophylaxis (prevention of first episode of bleeding), management of acute bleeding, and secondary prophylaxis (prevention of recurrent hemorrhage). The goal of this paper is to describe the current evidence behind the management of esophageal varices. We will discuss indications for primary prophylaxis and the different modes of therapy, pharmacological and interventional treatment in acute bleeding, and therapeutic options in preventing recurrent bleeding. The indications for TIPS will also be reviewed including its possible benefits in acute variceal hemorrhage.
doi:10.1155/2012/750150
PMCID: PMC3346976  PMID: 22577563
6.  The news of treatment of variceal upper gastrointestinal bleeding  
Journal of Medicine and Life  2011;4(4):395-398.
Variceal bleeding is one of the dreaded complications of portal hypertension. Although its prognosis has improved over the last several decades, it still carries substantial mortality. Although most portal hypertensive bleeds result from the ruptured distal esophageal varices, bleeding from other sources such gastric varices, portal hypertensive gastropathy, and ectopic varices can lead to clinically significant bleeding.
Variceal bleeding typically presents as massive gastrointestinal (GI) bleeding with hematemesis, melena or hematochezia. In general, the terapeutic aims of management are to initially correct hypovolemia, to control bleeding, to prevent complications of bleeding, such as infection and renal failure and to prevent early rebleeding.
The treatment of bleeding esophageal varices differs substantially foom the treatment of other lesions of the upper gastrointestinal tract. Moreover, patients with esophageal varices typically have severe liver disease and thus are likely from poor nutrition, blood clotting disorders, and encephalopathy, all of which can adversaly affect morbidity and mortality.
PMCID: PMC3227155  PMID: 22514572
stabilization of the patient’s hemodynamic status; severe liver disease; encephalopathy; rebleeding; mortality
7.  Pathophysiology of Portal Hypertension and Esophageal Varices 
Esophageal varices are the major complication of portal hypertension. It is detected in about 50% of cirrhosis patients, and approximately 5–15% of cirrhosis patients show newly formed varices or worsening of varices each year. The major therapeutic strategy of esophageal varices consists of primary prevention, treatment for bleeding varices, and secondary prevention, which are provided by pharmacological, endoscopic, interventional and surgical treatments. Optimal management of esophageal varices requires a clear understanding of the pathophysiology and natural history. In this paper, we outline the current knowledge and future prospect in the pathophysiology of esophageal varices and portal hypertension.
doi:10.1155/2012/895787
PMCID: PMC3362051  PMID: 22666604
8.  Use of ß-blocker therapy to prevent primary bleeding of esophageal varices 
Purpose: The purpose of this article is to educate nurse practitioners about the pathophysiology surrounding the development of portal hypertension and the effective use of nonselective ß-blockers to prevent primary bleeding and decrease the mortality risk.
Data sources: The articles included were retrieved via ISI Web of Science using the years 2004–2009 and key words cirrhosis, portal hypertension, esophageal varices, and beta-blockers. This information included scholarly books, journal reviews, retrospective chart reviews, and prospective randomized studies.
Conclusions: Cirrhosis is the leading cause of portal hypertension in Europe and North America. Esophageal varices are a result of the portosystemic collaterals the body develops to decompress the portal system. Hemorrhage from esophageal varices is a major cause of morbidity and mortality. Prevention of a primary bleed is the goal of therapy and is accomplished with nonselective ß-blockers.
Implications for practice: Very few patients with portal hypertension and esophageal varices are on ß-blockers. Use of nonselective ß-blockers has been found to lower portal pressure and decreases the risk of bleeding from esophageal varices and therefore decreases mortality. Patients unable to use ß-blockers can undergo endoscopic variceal ligation as an alternate method to reduce risk of bleeding.
doi:10.1111/j.1745-7599.2010.00567.x
PMCID: PMC3017746  PMID: 21129071
Beta-blocker; hepatology; gastroenterology; patient education
9.  Treatment of portal hypertension 
Portal hypertension is the main complication of cirrhosis and is defined as an hepatic venous pressure gradient (HVPG) of more than 5 mmHg. Clinically significant portal hypertension is defined as HVPG of 10 mmHg or more. Development of gastroesophageal varices and variceal hemorrhage are the most direct consequence of portal hypertension. Over the last decades significant advancements in the field have led to standard treatment options. These clinical recommendations have evolved mostly as a result of randomized controlled trials and consensus conferences among experts where existing evidence has been reviewed and future goals for research and practice guidelines have been proposed. Management of varices/variceal hemorrhage is based on the clinical stage of portal hypertension. No specific treatment has shown to prevent the formation of varices. Prevention of first variceal hemorrhage depends on the size/characteristics of varices. In patients with small varices and high risk of bleeding, non-selective β-blockers are recommended, while patients with medium/large varices can be treated with either β-blockers or esophageal band ligation. Standard of care for acute variceal hemorrhage consists of vasoactive drugs, endoscopic band ligation and antibiotics prophylaxis. Transjugular intrahepatic portosystemic shunt (TIPS) is reserved for those who fail standard of care or for patients who are likely to fail (“early TIPS”). Prevention of recurrent variceal hemorrhage consists of the combination of β-blockers and endoscopic band ligation.
doi:10.3748/wjg.v18.i11.1166
PMCID: PMC3309905  PMID: 22468079
Cirrhosis; Portal hypertension; Varices; Variceal hemorrhage; Primary prophylaxis; Secondary prophylaxis
10.  Long Term Variceal Sclerotherapy: Is Endoscopic Sclerosis a Unique Therapeutic Approach and a True Alternative to Surgery? 
HPB Surgery  1991;4(1):11-25.
Endoscopic sclerotherapy has been used to control acute variceal haemorrhage which persists despite conservative therapy, prevent recurrent variceal haemorrhage in patients with a history of oesophageal haemorrhage, and to prevent a haemorrhage in patients with oesophageal varices who never bled.
In this short paper I will cover our personal experience with more than 2000 patients receiving particularly paravariceal endoscopic sclerotherapy of bleeding esophageal varices, and especially present the results of our prospective and controlled randomized trials (Table 1) and underline the thesis that endoscopic sclerotherapy and surgical procedures for patients with portal hypertension are complementary supporting measures or options.
doi:10.1155/1991/32191
PMCID: PMC2423627  PMID: 1911473
11.  Prevention and Management of Variceal Hemorrhage 
Variceal hemorrhage is a common and devastating complication of portal hypertension and is a leading cause of death in patients with cirrhosis. The management of gastroesophageal varices has evolved over the last decade resulting in improved mortality and morbidity rates. Regarding the primary prevention of variceal hemorrhaging, nonselective β-blockers should be the first-line therapy in all patients with medium to large varices and in patients with small varices associated with high-risk features such as red wale marks and/or advanced cirrhosis. EVL should be offered in cases of intolerance or side effects to β-blockers, or for patients at high-risk for variceal bleeding who have medium or large varices with red wale marks or advanced liver cirrhosis. In acute bleeding, vasoactive agents should be initiated along with antibiotics followed by EVL or endoscopic sclerotherapy (if EVL is technically difficult) within the first 12 hours of presentation. Where available, terlipressin is the preferred agent because of its safety profile and it represents the only drug with a proven efficacy in improving survival. All patients surviving an episode of bleeding should undergo further prophylaxis to prevent rebleeding with EVL and nonselective β-blockers.
doi:10.1155/2013/434609
PMCID: PMC3626177  PMID: 23606973
12.  Application of Endoscopy in Improving Survival of Cirrhotic Patients with Acute Variceal Hemorrhage 
Playing a central role in the modern multidisciplinary management of acute gastroesophageal variceal hemorrhage, endoscopy is essential to stratify patient at risk, control active hemorrhage, and prevent first as well as recurrent bleeding. Before endoscopic procedure, antibiotic prophylaxis along with vasoactive medication is now routine practice. Intravenous erythromycin effectively cleanses stomach and may improve the quality of endoscopy. The timing of endoscopy should be on an urgent basis as delay for more than 15 hours after presentation is associated with mortality. Active variceal bleeding on endoscopy in a patient with hepatic decompensation heralds poor prognosis and mandates consideration of aggressive strategy with early portosystemic shunting. Band ligation has become the preferred modality to control and prevent bleeding from esophageal varices, although occasionally sclerotherapy may still be used to achieve hemostasis. Addition of pharmacotherapy with nonselective beta blockade to endoscopic ligation has become the current standard of care in the setting of secondary prophylaxis but remains controversial with inconsistent data for the purpose of primary prophylaxis. Gastric varices extending from esophagus may be treated like esophageal varices, whereas variceal obliteration by tissue glue is the endoscopic therapy of choice to control and prevent bleeding from fundic and isolated gastric varices.
doi:10.4061/2011/893973
PMCID: PMC3170849  PMID: 21994875
13.  Massive gastrointestinal bleeding due to isolated jejunal varices in a patient without portal hypertension 
INTRODUCTION
Isolated ectopic varices located in the small bowel are uncommon. Portal hypertension caused by liver cirrhosis is the most common predisposing risk factor.
PRESENTATION OF CASE
We present an unusual case of massive gastrointestinal bleeding from idiopathic jejunal varices in a 73-year-old Caucasian male without portal hypertension. Exploratory laparotomy disclosed ectopic varices located in the small intestine. Segmental resection of the jejunum with end to end anastomosis resulted in a complete resolution of the haemorrhage. During a 5 year follow up, the patient is stable with no bleeding recurrence.
DISCUSSION
Information on aetiology, diagnosis and management of jejunal varices is reviewed.
CONCLUSION
Diagnosis and management of isolated jejunal varices is challenging. Surgeons as well as acute care physicians have to consider idiopatic form of jejunal varices as a potential cause of gastrointestinal bleeding when gastroduodenoscopy and colonoscopy are negative.
doi:10.1016/j.ijscr.2013.01.029
PMCID: PMC3731695  PMID: 23528981
Jejunal varices; Gastrointestinal haemorrhage; Diagnosis; Management
14.  Medical and Endoscopic Management of Gastric Varices 
In the past 20 years, our understanding of the pathophysiology and management options among patients with gastric varices (GV) has changed significantly. GV are the most common cause of upper gastrointestinal bleeding in patients with portal hypertension after esophageal varices (EV) and generally have more severe bleeding than EV. In the United States, the majority of GV patients have underlying portal hypertension rather than splenic vein thrombosis. The widely used classifications are the Sarin Endoscopic Classification and the Japanese Vascular Classifications. The former is based on the endoscopic appearance and location of the varices, while the Japanese classification is based on the underlying vascular anatomy. In this article, the authors address the current concepts of classification, epidemiology, pathophysiology, and emerging management options of gastric varices. They describe the stepwise approach to patients with gastric varices, including the different available modalities, and the pearls, pitfalls, and stop-gap measures useful in managing patients with gastric variceal bleed.
doi:10.1055/s-0031-1284453
PMCID: PMC3312167  PMID: 22942544
Gastric varices; portal hypertension; liver cirrhosis; BRTO; TIPS; splenorenal shunt; cyanoacrylate
15.  Update on gastric varices 
Although less common than oesophageal variceal haemorrhage, gastric variceal bleeding remains a serious complication of portal hypertension, with a high associated mortality. In this review we provide an update on the aetiology, classification and management of gastric varices, including acute bleeding, prevention of rebleeding and primary prophylaxis. We describe the optimum management strategies for gastric varices including drug, endoscopic and radiological therapies, focusing on recent published evidence.
doi:10.4253/wjge.v6.i5.168
PMCID: PMC4024489  PMID: 24891929
Varices; Gastric; Portal hypertension; Tissue glue; Transjugular intrahepatic portosystemic shunt
16.  Management of Portal Hypertension in Children 
Management of portal hypertension in children has evolved over the past several decades. Portal hypertension can result from intrahepatic or extrahepatic causes. Management should be tailored to the child based on the etiology of the portal hypertension and on the functionality of the liver. The most serious complication of portal hypertension is gastroesophageal variceal bleeding, which has a mortality of up to 30%. Initial treatment of bleeding focuses on stabilizing the patient. Further treatment measures may include endoscopic, medical, or surgical interventions as appropriate for the child, depending on the cause of the portal hypertension. β-Blockers have not been proven to effectively prevent primary or secondary variceal bleeding in children. Sclerotherapy and variceal band ligation can be used to stop active bleeding and can prevent bleeding from occurring. Transjugular intrahepatic portosystemic shunts and surgical shunts may be reserved for those who are not candidates for transplant or have refractory bleeding despite medical or endoscopic treatment.
doi:10.1007/s11894-010-0151-y
PMCID: PMC3026674  PMID: 20927620
Portal hypertension; Pediatric; Variceal hemorrhage; Variceal ligation; Sclerotherapy; Balloon tamponade; Transjugular intrahepatic portosystemic shunt (TIPS); Surgical shunts; Octreotide; β-Blockers; Liver transplantation
17.  Treatment of Rare Gastric Variceal Bleeding in Acute Pancreatitis Using Embolization of the Splenic Artery Combined with Short Gastric Vein 
Case Reports in Gastroenterology  2012;6(3):741-746.
In the acute stage of pancreatitis, sinistral portal hypertension is a rare reason for gastric variceal bleeding. Here we report a 20-year-old female patient with massive upper gastrointestinal hemorrhage 7 days after an episode of severe acute pancreatitis. Computed tomography showed gastric varices caused by splenic venous thrombosis. Emergency endoscopic examination was performed, however tissue adhesive utilized to restrain the bleeding was not successful. Although interventional therapy was controversial to treat the gastric variceal hemorrhage resulting from sinistral portal hypertension, the bleeding was successfully treated by embolization of the splenic artery combined with short gastric vein. Two weeks after the interventional the patient was discharged from our hospital without recurrence of bleeding. Embolization of the splenic artery combined with short gastric vein proved to be an effective emergency therapeutic method for gastric variceal bleeding caused by sinistral portal hypertension in the acute stage of pancreatitis.
doi:10.1159/000345962
PMCID: PMC3531947  PMID: 23275766
Severe acute pancreatitis; Gastric varices; Splenic artery embolization
18.  Cerebral and splenic infarctions after injection of N-butyl-2-cyanoacrylate in esophageal variceal bleeding 
Variceal bleeding is the most serious complication of portal hypertension, and it accounts for approximately one fifth to one third of all deaths in liver cirrhosis patients. Currently, endoscopic treatment remains the predominant method for the prevention and treatment of variceal bleeding. Endoscopic treatments include band ligation and injection sclerotherapy. Injection sclerotherapy with N-butyl-2-cyanoacrylate has been successfully used to treat variceal bleeding. Although injection sclerotherapy with N-butyl-2-cyanoacrylate provides effective treatment for variceal bleeding, injection of N-butyl-2-cyanoacrylate is associated with a variety of complications, including systemic embolization. Herein, we report a case of cerebral and splenic infarctions after the injection of N-butyl-2-cyanoacrylate to treat esophageal variceal bleeding.
doi:10.3748/wjg.v19.i34.5759
PMCID: PMC3769917  PMID: 24039373
Cerebrum; Esophageal varix; Infarction; N-butyl-2-cyanoacrylate; Spleen
19.  Balloon-Occluded Retrograde Transvenous Obliteration of Gastric Varices: Concept, Basic Techniques, and Outcomes 
Patients with gastric variceal bleeding require a multidisciplinary team approach including hepatologists, endoscopists, diagnostic radiologists, and interventional radiologists. Upper gastrointestinal endoscopy is the first-line diagnostic and management tool for bleeding gastric varices, as it is in all upper gastrointestinal bleeding scenarios. In the United States when endoscopy fails to control gastric variceal bleeding, a transjugular intrahepatic portosystemic shunt (TIPS) traditionally is performed along the classic teachings of decompressing the portal circulation. However, TIPS has not shown the same effectiveness in controlling gastric variceal bleeding that it has with esophageal variceal bleeding. For the past 2 decades, the balloon-occluded retrograde transvenous obliteration (BRTO) procedure has become common practice in Asia for the management of gastric varices. BRTO is gaining popularity in the United States. It has been shown to be effective in controlling gastric variceal bleeding with low rebleed rates. BRTO has many advantages over TIPS in that it is less invasive and can be performed on patients with poor hepatic reserve and those with encephalopathy (and may even improve both). However, its by-product is occlusion of a spontaneous hepatofugal (TIPS equivalent) shunt, and thus it is contradictory to the traditional American doctrine of portal decompression. Indeed, BRTO causes an increase in portal hypertension, with potential aggravation of esophageal varices and ascites. This article discusses the concept, technique, and outcomes of BRTO within the broader management of gastric varices.
doi:10.1055/s-0032-1312573
PMCID: PMC3444869  PMID: 23729982
BRTO; transvenous obliteration; gastric; varices; TIPS; portal hypertension
20.  Balloon-occluded Retrograde Transvenous Obliteration (BRTO): Technical Results and Outcomes 
Variceal bleeding is one of the major complications of portal hypertension. Gastric variceal (GV) bleeding is less common than esophageal variceal (EV) bleeding, however, is associated with a high morbidity and mortality. Balloon-occluded retrograde transvenous obliteration (BRTO) is an established procedure for the management of gastric varices in Japan and has shown promising results in the past decade. The technical success rate, intent-to-treat (including technically failed BRTO-procedures) obliteration rate, and the obliteration rate of gastric varices of technically successful BRTO procedures was 91% (79–100%), 86% (73–100%), and 94% (75–100), respectively. BRTO is successful in controlling active gastric variceal bleeding in 95% of cases (91–100%) and in significantly reducing or resolving encephalopathy in 100% of cases. However, BRTO diverts blood into the portal circulation and increases the portal hypertension, thus aggravating esophageal varices with their potential for bleeding. The 1-, 2-, and 3-year esophageal variceal aggravation rates are 27–35%, 45–66%, and 45–91%, respectively. The gastric variceal rebleed rate of successful BRTO procedures, the intent-to-treat gastric variceal rebleed rate, and the global (all types of varices) variceal rebleed rate are 3.2–8.7%, 10–20%, and 19–31%, respectively. However, the advantage of diverting blood into the portal circulation and potentially toward the liver is improved hepatic function and possible patient survival. Unfortunately, the improved hepatic function is transient (for 6–12 months); however, it is preserved in the long-term (1–3 years). Patient 1-, 2-, 3-, and 5-year survival rates are 83–98%, 76–79%, 66–85%, and 39–69%, respectively. Patient survival is determined by baseline hepatic reserve and the presence of hepatocellular carcinoma.
doi:10.1055/s-0031-1284460
PMCID: PMC3312162  PMID: 22942551
BRTO; transvenous obliteration; varices; rebleeding; hepatic function; survival
21.  Update on the management of cirrhosis – focus on cost-effective preventative strategies 
Cirrhosis is a chronic liver disease stage that encompasses a variety of etiologies resulting in liver damage. This damage may induce secondary complications such as portal hypertension, esophageal variceal bleeding, spontaneous bacterial peritonitis, and hepatic encephalopathy. Screening for and management of these complications incurs substantial health care costs; thus, determining the most economical and beneficial treatment strategies is essential. This article reviews the economic impact of a variety of prophylactic and treatment regimens employed for cirrhosis-related complications. Prophylactic use of β-adrenergic blockers for portal hypertension and variceal bleeding appears to be cost-effective, but the most economical regimen for treatment of initial bleeding is unclear given that cost comparisons of pharmacologic and surgical regimens are lacking. In contrast, prophylaxis for spontaneous bacterial peritonitis cannot be recommended. Standard therapy for spontaneous bacterial peritonitis includes antibiotics, and the overall economic impact of these medications depends largely on their direct cost. However, the potential development of bacterial antibiotic resistance and resulting clinical failure should also be considered. Nonabsorbable disaccharides are standard therapies for hepatic encephalopathy; however, given their questionable efficacy, the nonsystemic antibiotic rifaximin may be a more cost-effective, long-term treatment for hepatic encephalopathy, despite its increased direct cost, because of its demonstrated efficacy and prevention of hospitalization. Further studies evaluating the cost burden of cirrhosis and cirrhosis-related complications, including screening costs, the cost of treatment and maintenance therapy, conveyance to liver transplantation, liver transplantation success, and health-related quality of life after transplantation, are essential for evaluation of the economic burden of hepatic encephalopathy and all cirrhosis-related complications.
doi:10.2147/CEOR.S30675
PMCID: PMC3632499  PMID: 23626470
hepatic encephalopathy; maintenance of remission; rifaximin; lactulose; cost
22.  Carvedilol in the Treatment of Portal Hypertension 
Variceal bleeding is a major event in the natural history of end-stage liver disease with a subsequent high mortality rate. Non-selective β-blockers are currently the drugs of choice for preventing first variceal bleeding. Endoscopic rubber band ligation of high risk varices features as a first line option if cirrhotic patients cannot tolerate β-blockers. Despite adequate β-blockade, some patients may still present with variceal bleeding. The effect of carvedilol, a non-selective β and α-1 receptor-blocker, on lowering portal pressure has been investigated in several clinical trials and found to be superior to propranolol in both acute and chronic hemodynamic studies. Recently, carvedilol has also been compared with band ligation for primary prophylaxis against variceal bleeding with equivalent results to band ligation. Patient tolerance to carvedilol in advanced liver disease remains a source of concern. This review examines the place of carvedilol as an alternative to the currently recommended pharmacological therapy in prophylaxis against variceal bleeding.
doi:10.4103/1319-3767.77251
PMCID: PMC3099066  PMID: 21372358
Band ligation; bleeding; carvedilol; portal hypertension; treatment; varices
23.  Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver 
Hepatology International  2008;2(4):429-439.
The Asian Pacific Association for the Study of the Liver (APASL) set up a Working Party on Portal Hypertension in 2002, with a mandate to develop consensus guidelines on various clinical aspects of portal hypertension relevant to disease patterns and clinical practice in the Asia-Pacific region. Variceal bleeding is a consequence of portal hypertension, which, in turn, is the major complication of liver cirrhosis. Primary prophylaxis to prevent the first bleed from varices is one of the most important strategies for reducing the mortality in cirrhotic patients. Experts predominantly from the Asia-Pacific region were requested to identify the different aspects of primary prophylaxis and develop the consensus guidelines. The APASL Working Party on Portal Hypertension evaluated the various therapies that have been used for the prevention of first variceal bleeding. A 2-day meeting was held on January 12 and 13, 2007, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and were subsequently presented at the annual conference of the APASL at Kyoto, Japan, in March 2007.
doi:10.1007/s12072-008-9096-8
PMCID: PMC2716901  PMID: 19669318
Varices; Cirrhosis; GI bleed; Guidelines
24.  Primary Prophylaxis of Variceal Hemorrhage in Children With Portal Hypertension: A Framework for Future Research 
Nonselective β-blocker therapy and endoscopic variceal ligation reduce the incidence of variceal hemorrhage in cirrhotic adults, but their use in children is controversial. There are no evidence-based recommendations for the prophylactic management of children at risk of variceal hemorrhage due to the lack of appropriate randomized controlled trials. In a recent gathering of experts at the American Association for the Study of Liver Diseases annual meeting, significant challenges were identified in attempting to design and implement a clinical trial of primary prophylaxis in children using either of these therapies. These challenges render such a trial unfeasible, primarily due to the large sample size required, inadequate knowledge of appropriate dosing of β-blockers, and difficulty in recruiting to a trial of endoscopic variceal ligation. Pediatric research should focus on addressing questions of natural history and diagnosis of varices, prediction of variceal bleeding, optimal approaches to β-blocker and ligation therapy, and alternative study designs to explore therapeutic efficacy in children.
doi:10.1097/MPG.0b013e318205993a
PMCID: PMC3728696  PMID: 21336158
endoscopic variceal ligation; esophageal varices; nonselective β-blockers; portal hypertension; primary prophylaxis; variceal bleeding
25.  Variceal pressure is a strong predictor of variceal haemorrhage in patients with cirrhosis as well as in patients with non-cirrhotic portal hypertension 
Gut  1999;45(4):618-621.
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.


Keywords: variceal haemorrhage; variceal pressure; non-cirrhotic portal hypertension
PMCID: PMC1727662  PMID: 10486375

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