Gastrointestinal varices

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Gastrointestinal varices were initially described as “dilated veins that bulge into the lumen, producing uneven worm like surface of the inside of esophagus. Varices in the gastrointestinal tract are thought to arise due to increased pressure in the portal venous system, leading to establishment of porto-systemic shunts. In the 20th century, sclerotherapy became an important treatment option in the management of variceal haemorrhage, especially with the advent of fibre-optic endoscopy. In 1950, The Sengstaken-Blakemore tube’s use was first described by Sengstaken and Blakemore and later used as a treatment option. Gastrointestinal varices may be further classified into esophageal and gastric varices. Esophageal varices may be further divided according to various classification systems such as the Dagradi classification, Conn’s classification, Pachquet classification, Westaby classification, Soehendra classification and Cales classification. Gastric varices may be classified according to Hoskins and Johnson’s classification, Mathur’s classification, Hashizume classification and Sarin’s classification system. Varices arise from hemodynamic disturbance between the systemic and portal venous system. The majority of venous drainage of the gastrointestinal system occurs via the portal venous system. Whenever there is an interruption of drainage through the portal system (for example due to cirrhosis), the vessels contributing to the porto-caval shunts become more prominent due to increased pressure gradient. The interruption in blood flow leads to the creation collateral vessels that involve veins of the esophagus, stomach, pelvis (hemorrhoids), retroperitoneum, liver, abdominal wall, and other areas. Causes of gastointestinal varices include all the causes of increased portal venous pressure, which may be divided into cirrhotic and non-cirrhotic causes. Non-bleeding varices are asymptomatic. Ruptured esophageal and gastric varices may lead to upper gastrointestinal bleeding and present with hematemesis. They must be differentiated from other causes of upper gastrointestinal bleeding such as peptic ulcer disease, esophagitis, gastritis, angiodysplasia, Dieulafoy’s lesion, vascular ectasia, Mallory-Weiss tears, aorto-enteric fistulas and upper gastrointestinal tumors. Gastroesophageal varices are present in approximately 50,000 per 100,000 patients with cirrhosis, depending upon the clinical stage of the disease. The annual incidence of gastrointestinal varices ranges from a low of 7,000 per 100,000 individuals to a high of 8,000 per 100,000 individuals. Variceal hemorrhage occurs at a rate of around 10%-15% per year. If left untreated, recurrent variceal hemorrhage occurs in 60% of patients, usually within 1-2 years of the initial hemorrhage. Complications include, transient dysphagia, chest pain, esophageal ulceration, ulcerogenic bleeding, post-therapeutic hemorrhage, esophageal strictures, pleural effusions, pericarditis and portal vein thrombosis. Factors associated with a poor prognosis of presence of bacterial infections, HVPG >20 mm Hg, alcohol intake and obesity. The AIMS65 score is the best predictor of mortality in patients with variceal bleeding. Esophagogastroduodenoscopy (EGD) is the gold standard test for the diagnosis of gastrointestinal varices. EGD should be performed once the diagnosis of cirrhosis is established. Physical examination of patients with gastrointestinal varices is usually remarkable for ascites, pallor, jaundice, tachycardia, low blood pressure in case of shock, hepatomegaly or shrunken liver (in case of cirrhosis), splenomegaly, altered mental status, palmar erythema, cyanosis and clubbing. X-ray taken after a barium swallow in cases of gastrointestinal varices may show multiple radiolucent filling defects. On CT scan gastrointestinal varices may appear as well-defined, tubular structures that have a smooth appearance with homogeneous attenuation. Upper endoscopy may be helpful in the diagnosis of gasteroesophageal varices. Findings on an upper endoscopy diagnostic of esophageal varices include visible submucosal tortuous veins, congested veins without compression during air insufflation, and grape-like varicose veins that may occlude the lumen. Medical therapy in cases of gastrointestinal varices includes goal-directed management of the cause of portal hypertension along with specific management of varices after their development. The treatment is aimed at optimizing portal venous inflow, portal pressure and portal resistance. The pharmacological therapy includes vasoconstrictors (beta blockers) and venodilators (nitrates). These therapies may be employed alone or in combination with endoscopic variceal ligation/sclerotherapy and transjugular intrahepatic shunt (TIPS) therapy depending upon the condition of the patient.

In 1850s, Sappey for the first time, described esophageal varices. In 1877, well before the role of portal hypertension in the development of variceal disease was understood, Nikolai Eck had already established the role of port-caval shunts to relieve animals from ascites. Popularly known as the ‘Eck fistula’, these shunts were employed in the treatment of eight dogs, seven of which died post-operatively and one escaped the laboratory. In 1906 Gilbert and Villaret coined the term ‘portal hypertension’. In 1928, Wolf first showed esophageal varices on thin barium roentgenograms as small dilated structures with a lumen. In 1931, Schatzki published the first findings of gastric varices on roentgenograms of five patients, followed by 45 further patients with esophageal and gastric varices in 1933. Varices were initially described as “dilated veins that bulge into the lumen, producing uneven worm like surface of the inside of esophagus. In 1939, Crafoord and Freckner discovered sclerotherapy with the help of quinine for the management of esophageal varices. In the 20th century, sclerotherapy became an important treatment option in the management of variceal haemorrhage, especially with the advent of fibre-optic endoscopy. In 1950, The Sengstaken-Blakemore tube’s use was first described by Sengstaken and Blakemore and later used as a treatment option. Ethanolamine oleate, sodium tetradecyl sulphate, polidocanol, sodium morrhuate and ethanol have been used as treatment options in sclerotherapy. In 1988, endoscopic variceal band ligation (EVBL) was first used for the treatment of esophageal varices, based on the concept of banding haemorrhoids with elastic O-rings. EVBL became a treatment option for the treatment of esophageal varices in 1990s. Antibiotics were recently used for the first time during the management of varices. Antibiotics were found to decrease the rate of bacterial infections, recurrent bleeding and improve mortality in patients bleeding from esophageal varices.

Gastrointestinal varices may be further classified into esophageal and gastric varices. Esophageal varices may be further divided according to various classification systems such as the Dagradi classification, Conn’s classification, Pachquet classification, Westaby classification, Soehendra classification and Cales classification. Gastric varices may be classified according to Hoskins and Johnson’s classification, Mathur’s classification, Hashizume classification and Sarin’s classification system. These classificatication systems are based on morphological features, anatomical location, size and color of the varices.

Varices arise from hemodynamic disturbance between the systemic and portal venous system. The majority of venous drainage of the gastrointestinal system occurs via the portal venous system. Whenever there is an interruption of drainage through the portal system (for example due to cirrhosis), the vessels contributing to the porto-caval shunts become more prominent due to increased pressure gradient. The interruption in blood flow leads to the creation of collateral vessels that involve veins of the esophagus, stomach, pelvis (hemorrhoids), retroperitoneum, liver, abdominal wall, and other areas.

Causes of gastointestinal varices include all the causes of increased portal venous pressure, which may be divided into cirrhotic and non-cirrhotic causes.

Non-bleeding varices are asymptomatic. Ruptured esophageal and gastric varices may lead to upper gastrointestinal bleeding and present with hematemesis. They must be differentiated from other causes of upper gastrointestinal bleeding such as peptic ulcer disease, esophagitis, gastritis, angiodysplasia, Dieulafoy’s lesion, vascular ectasia, Mallory-Weiss tears, aorto-enteric fistulas and upper gastrointestinal tumors.

Gastroesophageal varices are present in approximately 50,000 per 100,000 patients with cirrhosis, depending upon the clinical stage of the disease. The annual incidence of gastrointestinal varices ranges from a low of 7,000 per 100,000 individuals to a high of 8,000 per 100,000 individuals. Variceal hemorrhage occurs at a rate of around 10%-15% per year and depends on the severity of liver disease, size of varices, and presence of red wale marks (areas of thinning of the variceal wall).

The most potent risk factor for the development of gastrointestinal varices is increased portal venous pressure. Conditions that predispose an individual to development of increased portal venous pressure and consequently leading to varices can be divided into those leading to development of varices, those involved in progression of varices from small to large size and those leading to variceal hemorrhage.

Screening esophagogastroduodenoscopy (EGD) for the diagnosis of esophageal and gastric varices is recommended after the diagnosis of cirrhosis is made.

If left untreated, recurrent variceal hemorrhage occurs in 60% of patients, usually within 1-2 years of the initial hemorrhage. Gastrointestinal varices are an indication of increased portal venous pressure, especially in cirrhotic patients. The progressive increase in portal pressure leads to a progressive increase in size of the varices and an increased vascular wall tension. Variceal hemorrhage resulting from rupture occurs when the expanding force exceeds the maximal wall tension. Complications include, transient dysphagia, chest pain, esophageal ulceration, ulcerogenic bleeding, post-therapeutic hemorrhage, esophageal strictures, pleural effusions, pericarditis and portal vein thrombosis. Factors associated with a poor prognosis of presence of bacterial infections, HVPG >20 mm Hg, alcohol intake and obesity. The AIMS65 score is the best predictor of mortality in patients with variceal bleeding.

Esophagogastroduodenoscopy (EGD) is the gold standard test for the diagnosis of gastrointestinal varices. EGD should be performed once the diagnosis of cirrhosis is established.

Patients suffering from gastrointestinal varices may present with other co-morbid conditions which lead to portal hypertension. Chronic liver disease and portal vein thrombosis commonly lead to the development of gastrointestinal varices. Patients with a family history of venous abnormalities, hypercoaguable states, autosomal recessive polycystic kidney disease (may lead to hepatic fibrosis), nephronophthisis 1, Joubert syndrome and related disorders 5, cranioectodermal dysplasia (Sensenbrenner syndrome), Ellis-van Creveld syndrome, Jeune asphyxiating thoracic dystrophy, renal–hepatic–pancreatic dysplasia, autosomal dominant polycystic kidney disease have an increased risk of developing gastrointestinal varices. Non-bleeding gastrointestinal varices do not produce any symptoms, however bleeding gastrointestinal varices may lead to hematemesis, abdominal pain, lightheadedness, loss of consciousness, melena, bloody stools (in severe cases), shock (in case of loss of a large volume of blood).

Physical examination of patients with gastrointestinal varices is usually remarkable for ascites, pallor, jaundice, tachycardia, low blood pressure in case of shock, hepatomegaly or shrunken liver (in case of cirrhosis), spleenomegaly, altered mental status, palmar erythema, cyanosis and clubbing.

Cirrhosis of the liver is the most common cause of portal hypertension worldwide. A range of laboratory values may be obtained in the evaluation of cirrhosis, in order to determine disease severity and causation. Liver function tests, complete blood count, basic metabolic panel and coagulation factors are standard in the evaluation of cirrhosis. More specific testing for markers and serum enzymes may be performed when certain etiologies are suspected.

Electrocardiogram (EKG) in case of variceal bleeding after rupture may show sinus tachycardia.

Echo-Doppler may be helpful in the diagnosis of portal hypertension. Findings on an echo-doppler suggestive of portal hypertension include lack of increase in portal vein diameter in response to meals, increased portal blood flow velocity, and decreased portal vein cross-sectional area. Color-Doppler ultrasound may be helpful in the diagnosis of portal hypertension. Findings on a color-doppler ultrasound suggestive of portal hypertension include increased diameter of left gastric vein, increased diameter of portal vein, and increased flow velocity in left gastric vein. Biphasic and reverse flow in portal vein along with re-canalization of umbilical vein are pathognomonic for portal hypertension.

X-ray taken after a barium swallow in cases of gastrointestinal varices may show multiple radiolucent filling defects.

On CT scan gastrointestinal varices may appear as well-defined, tubular structures that have a smooth appearance with homogeneous attenuation.

There are no abnormal MRI findings associated with gastrointestinal varices.

Upper endoscopy may be helpful in the diagnosis of gasteroesophageal varices. Findings on an upper endoscopy diagnostic of esophageal varices include visible submucosaltortuous veins, congested veins without compression during air insufflation, and grape-like varicose veins that may occlude the lumen. Three dimensional portal venography may be helpful in the diagnosis of gasteroesophageal varices. Findings on a portal venography diagnostic of esophageal varices include reverse flow in porto-systemic shunts, collateral veins draining into inferior vena cava (IVC), and other collateral veins.

Hepatic venous pressure gradient (HVPG) is the difference between hepatic venous wedge pressure (HVWP) and free hepatic venous pressure (FHVP). HVPG reflects the intra-sinusoidal pressure. HVPG is measured through insertion of a catheter in right internal jugular vein.

Medical therapy in cases of gastrointestinal varices includes goal-directed management of the cause of portal hypertension along with specific management of varices after their development. The treatment is aimed at optimizing portal venous inflow, portal pressure and portal resistance. The pharmacological therapy includes vasoconstrictors (beta blockers) and venodilators (nitrates). These therapies may be employed alone or in combination with endoscopic variceal ligation/sclerotherapy and transjugular intrahepatic shunt (TIPS) therapy depending upon the condition of the patient.

Endoscopic procedures along with pharmacotherapy is the first line management of gastrointestinal varices. During endoscopic procedures the rate of hemostasis failure is almost 10%-20%, and mortality is approximately 60% if a second unsuccessful endoscopic treatment is performed without further intervention. In such situation surgical intervention may be required to achieve hemostasis and to stop the bleeding. Surgical shunts used for the management of bleeding gastrointestinal varices include pericardial devascularization plus proximal splenorenal shunt, Warren shunt, interposition shunts, caval-mesenteric shunts, end-to-end portacaval shunts with hepatic arterialization, left gastric vena-caval shunt and conventional splenorenal shunt. Non-shunting surgical procedures include ligation of varices and esophageal transection, splenic artery ligation and splenectomy.

Primary prevention of variceal bleeding may be achieved via rigorous surveillance of varices after their development and via the use non-selective beta blockers and/or endoscopic band ligation (EBL). Liver disease is the most common cause of portal hypertension and effective measures for the primary prevention of liver diseases includehepatitis B vaccination, avoidance from unprotected sexual intercourse, precise screening of the blood products before infusion, reducing alcohol consumption, obesityprevention, and diabetes mellitus prevention.

Secondary prevention of gastrointestinal varices involves prevention of rebleeding. The choice of method chosen for secondary prevention of gastrointestinal varices depends upon the condition of the patient, medication history and response to treatment. Methods used for secondary prevention include the use of beta blockers, band ligation, TIPS and liver transplantation.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

In 1850s, Sappey for the first time, described esophageal varices. In 1877, well before the role of portal hypertension in the development of variceal disease was understood, Nikolai Eck had already established the role of port-caval shunts to relieve animals from ascites. Popularly known as the ‘Eck fistula’, these shunts were employed in the treatment of eight dogs, seven of which died post-operatively and one escaped the laboratory. In 1906 Gilbert and Villaret coined the term ‘portal hypertension’. In 1928, Wolf first showed esophageal varices on thin barium roentgenograms as small dilated structures with a lumen. In 1931, Schatzki published the first findings of gastric varices on roentgenograms of five patients, followed by 45 further patients with esophageal and gastric varices in 1933. Varices were initially described as “dilated veins that bulge into the lumen, producing uneven worm like surface of the inside of esophagus. In 1939, Crafoord and Freckner discovered sclerotherapy with the help of quinine for the management of esophageal varices. In the 20th century, sclerotherapy became an important treatment option in the management of variceal haemorrhage, especially with the advent of fibre-optic endoscopy. In 1950, The Sengstaken-Blakemore tube’s use was first described by Sengstaken and Blakemore and later used as a treatment option. Ethanolamine oleate, sodium tetradecyl sulphate, polidocanol, sodium morrhuate and ethanol have been used as treatment options in sclerotherapy. In 1988, endoscopic variceal band ligation (EVBL) was first used for the treatment of esophageal varices, based on the concept of banding haemorrhoids with elastic O-rings. EVBL became a treatment option for the treatment of esophageal varices in 1990s. Antibiotics were recently used for the first time during the management of varices . Antibiotics were found to decrease the rate of bacterial infections, recurrent bleeding and improve mortality in patients bleeding from esophageal varices.

• In 1543, Vesalius discovered the mapping of the portal venous system.
• In the 1700s, Morgagni descried the process of “portal hypertensive bleeding”.^[1]
• In 1805, Philip Bozzini created a special tube, naming it the ‘Lichtleiter’ or ‘light-guiding instrument’ for examining the urinary tract. This was later termed as ‘endoscope’ by a French surgeon named Antoine Jean Desormeaux. In 1868, Adolph Kussmaul first used the endoscope to examine the stomach of a patient.^[2]
• In 1841, Raciborski was the first to discover collateral blood circulation between systemic and portal systems, specifically the short gastric and hemorrhoidal veins.^[3]
• In 1850s, Sappey for the first time, described esophageal varices.^[4]
• In 1877, well before the role of portal hypertension in the development of variceal disease was understood, Nikolai Eck had already established the role of port-caval shunts to relieve animals from ascites. Popularly known as the ‘Eck fistula’, these shunts were employed in the treatment of eight dogs, seven of which died post-operatively and one escaped the laboratory.^[3]
• In 1881, Johann von Mikulicz, a Polish-Austrian surgeon, invented and used ‘gastroscope’, for examination of the esophagus, stomach and small intestine.^[5]
• In 1903 Vidal, successfully created an Eck fistula was used a treatment option in a human suffering from ascites.
• In 1906 Gilbert and Villaret coined the term ‘portal hypertension’.^[6]
• In 1928, Wolf first showed esophageal varices on thin barium roentgenograms as small dilated structures with a lumen.^[3]
• This was further confirmed by case reports and series by Berg (1931), Hjelm (1931), Kirklin (1931), Beutel (1932) and Oppenheimer (1937), demonstrating the presence of esophageal varices on barium studies
• In 1931, Schatzki published the first findings of gastric varices on roentgenograms of five patients, followed by 45 further patients with esophageal and gastric varices in 1933.^[3]
• Varices were initially described as “dilated veins that bulge into the lumen, producing uneven worm like surface of the inside of esophagus.
• In 1936, Rousselot on patients with ‘Banti’s syndrome’ shed light on elevated portal pressure.^[7]
• During the same year, Crafoord and Freckner, two Swedish surgeons, first reported their use of rigid gastroscopes to visualize bleeding varices and stop the bleeding process via sclerotherapy with quinine-urethane.^[3]
• In 1937, Thomson and colleagues confirmed these findings by measuring portal pressures during celiotomy procedures, further stressing the importance of portal hypertension in the development of varices.^[3]

• In 1939, Crafoord and Freckner discovered sclerotherapy with the help of quinine for the management of esophageal varices.^[8]
• In the 20th century, sclerotherapy became an important treatment option in the management of variceal haemorrhage, especially with the advent of fibre-optic endoscopy.
• Prior to the 1970s, surgery was the mainstay of therapy for variceal hemorrhage.
• Esophageal stapling or esophagectomy were previously being used for management of gastrointestinal varices but were associated with high mortality rates from sepsis, hepatic failure and renal failure.^[9]
• In the 1980s, in patients with portal hypertension, devascularisation procedures were associated with decreased mortality in patients.
• In the late 20th century, splenectomy became a famous procedure for management of gastrointestinal varices.
• Surgical therapies are employed in patients who have failed endoscopic procedures.
• In 1950, The Sengstaken-Blakemore tube’s use was first described by Sengstaken and Blakemore and later used as a treatment option.
• It has been largely replaced by endoscopic therapies.

• In the early 1970s, the first reported case series of endoscopic sclerotherapy was published with its use becoming more widespread in the 1980s.
• Ethanolamine oleate, sodium tetradecyl sulphate, polidocanol, sodium morrhuate and ethanol have been used as treatment options in sclerotherapy.
• In Europe the most commonly used agents were ethanolamine oleate and polidocanol, whereas in the United States sodium morrhuate was employed as a treatment strategy.
• Para-variceal injection consisted of injection in the vicinity of the varix causing variceal occlusion by tamponade resulting in submucosal fibrosis of tissue around the varix, on the other hand, intra-variceal injection lead to thrombosis and resultant occlusion of the lumen.
• Sclerotherapy when compared to placebo and baloon tamponade has been shown to significantly control bleeding from varices
• In 1988, endoscopic variceal band ligation (EVBL) was first used for the treatment of esophageal varices, based on the concept of banding hemorrhoids with elastic O-rings. EVBL became a treatment option for the treatment of esophageal varices in 1990s

• In the 1990s, sclerotherapy became a popular treatment option not only for esophageal varices but gastric varices as well.
• EVBL became increasingly popular treatment modality for esophageal varices in the 1990s.
• To achieve higher success rates in endoscopic therapies, pharmacological therapies for example, the use of octreotide, telipressin and somatostatin were developed for better control of variceal hemorrhage.
• Transjugular intrahepatic portosystemic shunt (TIPSS) which involves placement of a stent between the portal vein and hepatic vein to reduce portal pressure, was used as a radiological treatment option for varices for the first time in 1990s.

• During the 21st century, pharmacological, endoscopic and radiological therapies for variceal haemorrhage became optimized.
• Antibiotics were used for the first time during the management of varices. Antibiotics were found to decrease the rate of bacterial infections, recurrent bleeding and improve mortality in patients bleeding from esophageal varices.
• Cyanoacrylate glue was shown to have a faster rate of variceal obliteration when compared to ethanol injection in sclerotherapy.
• In the early 2000s, thrombin was also used for variceal obliteration.
• In 2004, the use of a covered TIPS stent (covered with polytetrafluoroethylene) was approved by the United States Food and Drug Administration
• In the 2000s, interventional radiological procedures for the treatment of gastric varices included the use of balloon-occluded retrograde transvenous obliteration (BRTO) as rescue therapy when endoscopic obturation therapy failed.
• Although, liver transplantation is the only curative treatment for liver cirrhosis at this point in time, its role in the management of varices is unknown.
• Another new area of interest that has been the development of haemostatic powders/sprays. TC-325 (Hemospray, Cook Technology™) is a granular non absorbable mineral powder used in the management of arterial wounds

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Gastrointestinal varices may be further classified into esophageal and gastric varices. Esophageal varices may be further divided according to various classification systems such as the Dagradi classification, Conn’s classification, Pachquet classification, Westaby classification, Soehendra classification and Cales classification. Gastric varices may be classified according to Hoskins and Johnson’s classification, Mathur’s classification, Hashizume classification and Sarin’s classification system. These classificatication systems are based on morphological features, anatomical location, size and color of the varices.

The following table outlines the major classification schemes for esophageal varices, based on grades, taking into account morphological features, size and anatomical location:^{[1][2][3][4][5][6][7][8][9][10][11][12][13]}

Classification system	Grade	Interpretation of grade
Dagradi classification	1	Blue or red discoloration of varices Become prominent on compression of esophageal wall by esophagoscope Linear/sigmoid shaped < 2 mm in diameter
	2	Bluish in color 2–3 mm in diameter Mildly tortuous or straight Elevated above the surface or the relaxed esophagus
	3	Prominently elevated bluish veins 3–4 mm in diameter Straight or tortuous
	4	Bluish varices > 4 mm in diameter, which completely surround the esophageal lumen and almost meet in the mid-lumen Tortuous Closely packed around the wall With or without mucosal cover
	5	Grape-like appearance Occlude the lumen of the advancing esophagoscope Presence of small, cherry-red varices on top of a base of bluish varices
Conn’s classification	I	Varices visible during only one phase of respiration
	II	Varices visible during both phases of respiration
	III	3-6 mm in diameter
	IV	> 6 mm in diameter
Paquet’s classification	I	Microcapillaries located in : Distal esophagus Esophago–gastric junction
	II	1-2 variceal vessels located in the distal esophagus
	III	Medium-sized varices of any number
	IV	Large-sized varices in any part of esophagus
Westaby classification	1	Varices protruded above mucosa May be depressed with insufflations.
	2	Varices covering <50% of the lumen
	3	Varices covering >50% of the lumen
Soehendra classification	I	Mild dilatation Diameter <2 mm More prominent on flexing the neck forward
	II	Moderate dilatation Tortuous Diameter 3–4 mm Located in the lower part of the esophagus
	III	Total dilatation Diameter >4 mm Thin-walled Varices superimposed on varices Located in the gastric fundus
	IV	Total dilatation Found in the entire esophagus Simultaneous presence of gastric or duodenal varices
Calès classification	1	Varices flattened by insufflations
	2	Varices not flattened by insufflations
	3	Confluent esophageal varices not flattened by insufflations

The following table outlines the major classification systems adapted for classifying gastric varices:^{[14][15][16][17][18][19]}

Classification system	Grade	Interpretation of grade
Hoskins and Johnson’s classification	1	Extension of esophageal varices across the squamo–columnar junction
	2	Varices located in gastric fundus Overlap with esophageal varices in the esophagus at cardiac end
	3	Gastric varices in gastric fundus or body No esophageal varices
Mathur’s classification	1	Esophageal varices with lesser curvature varices
	2	Esophageal varices with gastric fundal varices 2a – Subcardiac 2b – Diffuse fundal
	3	Isolated fundal varix 3a – Secondary to splenic vein thrombosis 3b – Secondary to generalized portal hypertension
	4	Lesser curvature gastric varices Esophageal varices along with varices located in the gastric fundus
	5	Varices in the gastric antrum
Hashizume’s classification	Form	Three forms: F1: Tortuous F2: Nodular F3: Tumorous
	Location	Five common locations: La: Anterior Lp: Posterior Ll: Lesser curvature of the stomach L: Greater curvature cardiac of the stomach Lf: Fundic areas of the stomach
	Color	Three colors: Cr: Red Cw: White RCS: Thin-walled focal redness on the varix as red colored spot
Sarin’s classification	Gastro-esophageal type 1	Esophageal varices spreading into the lesser curvature of the stomach
	Gastro-esophageal type 2	Esophageal varices spreading into the greater curvature of the stomach
	Isolated gastric type 1	Varices in the gastric fundus and cardia without esophageal varices
	Isolated gastric type 2	Varices outside of cardio–fundal region or first part of duodenum

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Varices arise from hemodynamic disturbance between the systemic and portal venous system. The majority of venous drainage of the gastrointestinal system occurs via the portal venous system. Whenever there is an interruption of drainage through the portal system (for example due to cirrhosis), the vessels contributing to the porto-caval shunts become more prominent due to increased pressure gradient. The interruption in blood flow leads to the creation collateral vessels that involve veins of the esophagus, stomach, pelvis (hemorrhoids), retroperitoneum, liver, abdominal wall, and other areas.

Varices arise from hemodynamic disturbance between the systemic and portal venous system. The majority of venous drainage of the gastrointestinal system occurs via the portal venous system. Whenever there is an interruption of drainage through the portal system (for example due to cirrhosis), the vessels contributing to the porto-caval shunts become more prominent due to increased pressure gradient. The interruption in blood flow leads to the creation collateral vessels that involve veins of the esophagus, stomach, pelvis (hemorrhoids), retroperitoneum, liver, abdominal wall, and other areas.^[1][2]

Esophageal varices are a major complication of portal hypertension (increased blood pressure in the portal venous system). In order to understand the mechanism leading to the development of esophageal varices, it is important to understand the normal vascular architecture and venous drainage of the esophagus.^[3]

Vascular architecture and venous drainage of esophagus

• Vascular resistance increases against portal blood flow in cirrhosis, non-cirrhotic portal fibrosis, idiopathic portal hypertension, extra-hepatic portal vein obstruction, Budd-Chiari syndrome, and other portal hypertensive disorders, inducing congestion of blood in the splenic and mesenteric veins that lie upstream of the portal trunk^[4][5][6]
• The major vessels draining blood from the esophagus include, the left gastric and less frequently short gastric veins^[7][8]

Porto-caval collaterals in esophagus

• Portal hypertension develops due to the formation of porto-collateral circulation^[9]
• Dilatation and hypertrophy of preexisting vascular channels lead to the formation of these collateral channels^[10]
• Collaterals develop according to the increased portal pressure, and minimum threshold level of hepatic–venous portal gradient may be 10 mmHg for the development of porto-systemic collaterals and esophageal varices^[11]

Role of hepatic vasodilators

(a) Nitric Oxide (NO)

• Nitric oxide (NO) acts as an intra-hepatic vasodilator^[12][13]
• The levels of NO are decreased in patients suffering from chronic liver disease^[14]
• This leads to an imbalance between the endogenous vasodilators and vasoconstrictors inside the hepatic vascular tree
• Reduced levels of hepatic NO production may contribute to the increased intra-hepatic vascular resistance in cirrhosis, thereby worsening portal hypertension^[15]
• NO-dependent apoptosis maintains the hepatic sinusoidal homeostasis
• NO also leads to apoptosis of hepatic stellate cells through a signaling mechanism that involves mitochondria, and a decreased level of NO may lead to a disturbance of the intra-hepatic homeostasis^[16]

(b) Glucagon

• Glucagon is a hormonal vasodilator which is associated with increased blood flow in the splanchnic bed and portal hypertension^[17]
• Plasma glucagon levels are increased in cirrhotic patients due to decreased hepatic clearance of glucagon as well as an increased secretion of glucagon by pancreatic alpha cells^[17][18] 
• Hyperglucagonemia may play a part in splanchnic vasodilatation of chronic portal hypertension^[19][20][21]

(c) Prostacyclin

• Prostacyclin is an endogenous vasodilator^[22][23]
• Prostacyclin levels are inversely related to the size of varices^[24][25]
• Decreased prostacyclin levels are found in cirrhotic patients

Role of hepatic vasoconstrictors

(a) Endothelin

• Endothelin is involved in changes in the vascular tone in cirrhotic patients^[26]
• Endothelin leads to increased vascular tone (vasoconstriction)
• Endothelin 1 and endothelin 3 are increased in cirrhosis^[27][28]

(b) Angiotensin II

• Angiotensin II leads to increased intra-portal resistance via vasoconstriction^[29]

(c) Norepinephrine

• Norepinephrine is also a vasoconstrictor, which controls the intra-hepatic vascular tone, including portal vessels^[30][31]

Role of endothelial dysfunction

• Vascular endothelium harbors a number of vasocontrictive substance such as, prostaglandin H2(PGH2), thromboxane A2 (TXA2) and anion superoxide, which contribute to portal hypertension^[32]
• Cirrhosis leads to endothelial dysfunction^[33]
• Increased production of prostanoids, most likely thromboxane A2 (TXA2) has been known to be associated with endothelial dysfunction^[34]

Mechanism leading to variceal hemorrhage

• The wall tension of the vessel determines if there will be rupture of the varices^[35]
• The wall tension depends upon the variceal pressure, luminal pressure and radius of the vessel^[35]
• The wall tension is calculated by using the “Laplace’s law”:
  • Wall tension = (variceal pressure – luminal pressure) × radius/thickening of variceal wall.
  • The result is the force which is generated by the variceal wall opposing further dilation
• When the wall tension overcomes the elastic limit of the varices, rupture occurs^[36]

Gastric varices may form secondary to chronic liver disease or splenic vein obstruction; splenic vein obstruction may be caused by pancreatitis, pancreatic pseudocysts, pancreatic carcinoma, other retroperitoneal tumors, or intrinsic thrombosis of the splenic vein

• Vascular architecture and venous drainage of stomach

• Gastric varices consist of dilated veins present in the submucosa of the stomach in areas of port-caval anastomosis (fundus and cardia)
• The splenic vein and superior mesenteric vein join together to form the portal vein. The anastomosis contributing to gastric varices consists of short gastric vein, left gastric vein and esophageal branches
• Cardiac varices are supplied majorly by left gastric vein
• Fundic varices are supplied by short gastric or posterior gastric veins^[37]
• Cardiac and fundic varices differ in the degree of anastomosis (more common in cardiac varices) and the caliber of the varicose veins

Mechanism of development of gastric varices

• Increased pressure in two main venous pathways are responsible development of gastric varices

(a) Cardiac varices

• First, through the right and left gastric veins, which drain varices around the distal esophagus and cardia (EV and GOV1) into the portal vein, or when flow is reversed the blood flows backwards into the azygous system

(b) Fundic varices

• Blood from the fundus of the stomach is drained via the short gastric and posterior gastric veins, these veins give rise to the fundic varices
• In portal hypertension, the flow often is reversed and blood drains from the spleen toward the stomach into fundal varices (GOV2 and IGV1)
• IGV2 often are caused by dilation of branches of the gastroepiploic veins

Mechanism leading to variceal hemorrhage

• The wall tension of the vessel determines if there will be rupture of the varices^[35]
• The wall tension depends upon the variceal pressure, luminal pressure and radius of the vessel^[35]
• The wall tension is calculated by using the “Laplace’s law”:
  • Wall tension = (variceal pressure – luminal pressure) × radius/thickening of variceal wall.
  • The result is the force which is generated by the variceal wall opposing further dilation
• When the wall tension over comes the elastic limit of the varices, rupture occurs^[36]
• The vessel wall of the varix is covered by a thinned out serosa and mucosa, and the varix comes to be seen through from the serosa as well as from the mucosa. When such a large varix ruptures, bleeding is profuse and difficult to manage, and the mortality rate is high

Congenital syndromes leading to gastrointestinal varices may involve genetic mutations in the following genes:^[38][39][40]

Pattern of inheritance	Disease	Locus	Gene
Autosomal recessive	Autosomal recessive polycystic kidney disease (ARPKD)	PKHD1	PKHD1
	Nephronophthisis 1	NPHP1 2	NPHP1
		NPHP2	INVS
		NPHP3	NPHP3
		NPHP4	NPHP4
		NPHP5 (SLSN5)	IQCB1
		NPHP6 3 (SLSN6)	CEP290
		NPHP7	GLIS2
		NPHP8 4	RPGRIP1L
		NPHP9	NEK8
		NPHP11	TMEM67
		NPHP12	TTC21B
		NPHP13	WDR19
		NPHP14	ZNF423
		NPHP15	CEP164
		NPHP16	ANKS6
	Joubert syndrome and related disorders 5	JBTS1	INPP5E
		JBTS2	TMEM216
		JBTS3	AHI1
		JBTS4 2	NPHP1
		JBTS5 3	CEP290
		JBTS6 6	TMEM67
		JBTS7 4	RPGRIP1L
		JBTS8	ARL13B
		JBTS9	CC2D2A
		JBTS10	OFD1
		JBTS11	TTC21B
		JBTS12	KIF7
		JBTS13	TCTN1
		JBTS14	TMEM237
		JBTS15	CEP41
		JBTS16	TMEM138
		JBTS17	C5orf42
		JBTS18	TCTN3
		JBTS19	ZNF423
		JBTS20	TMEM231
			TCTN2
	Bardet-Biedl syndrome 7	BBS1	BBS1
		BBS2	BBS2
		BBS3	ARL6
		BBS4	BBS4
		BBS5	BBS5
		BBS6	MKKS
		BBS7	BBS7
		BBS8	TTC8
		BBS9	BBS9
		BBS10	BBS10
		BBS11	TRIM32
		BBS12	BBS12
		BBS13 8	MKS1
		BBS14 3	CEP290
	Meckel syndrome 9	MKS1 8	MKS1
		MKS2	TMEM216
		MKS3 5	TMEM67
		MKS4 3	CEP290
		MKS5 4	RPGRIP1L
		MKS6	CC2D2A
		MKS7	NPHP3
		MKS8	TCTN2
		MKS9	B9D1
		MKS10	B9D2
		MKS11	TMEM231
	Cranioectodermal dysplasia		IFT122
	Ellis-van Creveld syndrome	EVC 10	EVC
EVC2
Jeune asphyxiating thoracic dystrophy	JATD1	Unknown
	JATD2	IFT80
Renal–hepatic–pancreatic dysplasia		NPHP3
X-linked	OFD1		OFD1
Autosomaldominant	Autosomal dominant polycystic kidney disease (ADPKD)	PKD1	PKD1
		PKD2	PKD2

On gross examination, the following findings may be observed in gastrointestinal varices:

• Linear dark blue submucosal dilated veins
• In case of bleeding the varix may be colored dark red

On microscopic examination the following findings may be observed:^[41][42]

• Very thin parallel veins in the lamina propria mucosae in the palisade zone become enlarged in portal hypertension and join the few larger submucosal veins to form esophageal varices
• The location of esophageal and gastric varices within the wall of gastrointestinal tract is different:
  • Esophageal varices: Lamina propria mucosae and submucosa
  • Gastric varices: Submucosa
• The wall of the varix (vein) may show deficiency in smooth muscle cells and elastic fibers and disproportionate increase in fibrous tissue

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Causes of gastointestinal varices include all the causes of increased portal venous pressure, which may be divided into cirrhotic and non-cirrhotic causes.

• Gastrointestinal varices (especially esophageal and gastric) are due to increased pressure in the portal venous system
• The major causes of portal hypertension may be broadly categorized into cirrhotic and non-cirrhotic^{[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]}

• Chronic hepatitis (B or C)

Pre-hepatic causes

• Portal vein thrombosis
• Splenic vein thrombosis
• Splanchnic arteriovenous fistula
• Splenomegaly (eg, from lymphoma, Gaucher’s disease)

Intrahepatic causes^{[1][5][6][7][8][9][10][11][12][13][14][17][18][19][20]}

• Presinusoidal:
  • Schistosomiasis
  • Idiopathic non-cirrhotic portal hypertension (including nodular regenerative hyperplasia)
  • Primary biliary cirrhosis
  • Sarcoidosis
  • Congenital hepatic fibrosis
  • Primary sclerosing cholangitis
  • Hepatic arteriopetal fistula
  • Adult polycystic liver disease
  • Arteriovenous fistulas
  • Autoimmune cholangiopathy
  • Vinyl chloride toxicity
  • Neoplastic occlusion of the intra-hepatic portal vein
  • Mineral oil granuloma
• Sinusoidal:
  • Arsenic poisoning
  • Vinyl chloride toxicity
  • Drugs (eg, amiodarone, methotrexate)
  • Alcoholic liver disease
  • Nonalcoholic fatty liver disease
  • Gaucher’s disease
  • Zellweger syndrome
  • Viral hepatitis
  • Chronic Q fever
  • Schistosomiasis
  • Amyloid or light-chain deposition in the space of Disse
  • Acute hepatic injury
  • Mastocytosis
  • Agnogenic myeloid metaplasia
  • Acute fatty liver of pregnancy
• Postsinusoidal:
  • Sinusoidal obstruction syndrome (venoocclusive disease)
  • Budd-Chiari syndrome
  • Alcoholic liver disease
  • Chronic radiation injury
  • Vitamin A toxicity
  • Epithelioid hemangioendothelioma
  • Angiosarcoma
  • Sarcoidosis
  • Mycobacterium avium or M. intracellulare infection
  • Mineral oil granuloma

Post-hepatic:^[3][4]

• Inferior vena cava (IVC) obstruction (eg, Budd-Chiari syndrome)
• Cardiac disease (constrictive pericarditis, restrictive cardiomyopathy)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Non-bleeding varices are asymptomatic. Ruptured esophageal and gastric varices may lead to upper gastrointestinal bleeding and present with hematemesis. They must be differentiated from other causes of upper gastrointestinal bleeding such as peptic ulcer disease, esophagitis, gastritis, angiodysplasia, Dieulafoy’s lesion, vascular ectasia, Mallory-Weiss tears, aorto-enteric fistulas and upper gastrointestinal tumors.

Ruptured esophageal and gastric varices may lead to upper gastrointestinal bleeding and present with hematemesis. It must be differentiated from other causes of upper gastrointestinal bleeding. The following table outlines the differentials:^{[1][2][3][4][5][6][7]}

Disease/Cause	Bleeding manifestations				Symptoms				Risk factors	Endoscopic findings
	Hematemesis	Melena	Hematochezia	Occult blood	Abdominal pain	Dysphagia	Dyspepsia	Weighloss
Ulcerative or erosive
Peptic ulcer disease	+	+	+	+	+	–	+	+/-	NSAIDs Infections: Helicobacter pylori CMV HSV Stress ulcer ZES	Ulcer with smooth, regular, rounded edges Ulcer base often filled with exudate Examination of the ulcer may reveal: Active bleeding Nonbleeding visible vessel Adherent clot Flat pigmented spot Clean ulcer base
Esophagitis	+	+	–	+	–	+	–	–	Gastroesophageal reflux disease Medications: Tetracycline Doxycycline Clindamycin Trimethoprim-sulfamethoxazole NSAIDs Bisphosphonates Potassium chloride Quinidine Iron supplements  Infections: HSV CMV Candida albicans HIV	Peptic esophagitis The ulcerations are usually irregularly shaped or linear, multiple, and distal. Pill-induced Ulcerations are usually singular and deep, occurring at points of stasis (especially near the carina), with sparing of the distal esophagus Infectious esophagitis: HSV – Discrete, superficial ulcers, with well-demarcated borders that tend to involve the upper or mid-esophagus; vesicles may be seen CMV – Ulcers range from small and shallow to large (>1 cm) and deep; most patients have multiple lesions Candida – Diffuse white plaques HIV – Tends to involve the mid to distal esophagus, ulcers may be shallow or deep, and may be large
Gastritis/gastropathy	+	+	–	+	+	–	+	–	Risk factors: H. pylori NSAIDs Excessive alcohol consumption Radiation injury Physiologic stress Weight loss surgery Bile reflux Risk factors for bleeding: Anticoagulant use	Erythematous mucosa Superficial erosions Nodularity Diffuse oozing
Complications of portal hypertension
Esophagogastric varices	+	+	+	–	+	–	–	–	Portal hypertension from: Cirrhosis Portal vein thrombosis	Vascular structures that protrude into the esophageal and/or gastric lumen Findings associated with an increased risk of hemorrhage: Longitudinal red streaks on the varices (red wale marks) Cherry-colored spots that are flat and overlie varices Raised, discrete red spots
Ectopic varices	+	+	+	–	–	–	–	–		Vascular structures that protrude into areas of the gastrointestinal tract lumen other than the esophagus or stomach (eg, small bowel, rectum)
Portal hypertensive gastropathy	+	+	+	+	+	–	–	–		Mosaic-like pattern that gives the gastric mucosa a “snakeskin” appearance
Vascular lesions
Angiodysplasia	+	+	+	+	–	–	–	–	End-stage renal disease Aortic stenosis Hereditary hemorrhagic telangiectasia Von Willebrand disease Radiation therapy	Small (5 to 10 mm), flat, cherry-red lesions, often with a fern-like pattern of arborizing, ectatic blood vessels radiating from a central vessel.
Dieulafoy’s lesion	+	+	+	–	+	–	–	–	Bleeding may be associated with NSAIDs use Hypertension Chronic kidney disease Diabetes Alcohol abuse	Usually located in the proximal stomach May have active arterial spurting from the mucosa without an associated ulcer or mass If the bleeding has stopped, there may be a raised nipple or visible vessel without an associated ulcer
Gastric antral vascular ectasia	+	+	+	+	+	–	–	–	Cirrhosis with portal hypertension Chronic kidney disease Diabetes mellitus Scleroderma Bone marrow transplantation	Longitudinal rows of flat, reddish stripes radiating from the pylorus into the antrum.
Traumatic or iatrogenic
Mallory-Weiss syndrome	+	+	+	–	–	–	–	–	Vomiting/retching (often related to alcohol consumption) Straining at stool or lifting Coughing Seizures Blunt abdominal trauma Hiatal hernia	Tear in the esophagogastric junction. Usually singular and longitudinal, but may be multiple. The tear may be covered by an adherent clot.
Foreign body ingestion	+	+	+	+	–	+	–	–	Psychiatric disorders Dementia Loose dentures	Visualization of the foreign body endoscopically.
Post-surgical anastomotic hemorrhage (marginal ulcers)	+	+	+	+	+	–	+	–	Gastric bypass surgery NSAID use H. pylori infection Smoking	Ulceration/friable mucosa at an anastomotic site.
Aortoenteric fistula	+	+	+	–	+	–	–	–	Infectious aortitis Prosthetic aortic graft Atherosclerotic aortic aneurysm Penetrating ulcers Tumor invasion Trauma Radiation injury Foreign body perforation	Endoscopy may reveal a graft, an ulcer or erosion at the site Adherent clot, or an extrinsic pulsatile mass in the distal duodenum or esophagus.
Tumors
Upper GI tumors	+	+	+	+	+	+	+	+	History of alcoholism, smoking	Ulcerated mass in the esophagus, stomach, or duodenum. In gastric malignancies: The folds surrounding the ulcer crater may be nodular, clubbed, fused, or stop short of the ulcer margin The margins may be overhanging, irregular, or thickened Bleeding lymphoma may appear as An ulcerated mass Polypoid lesion As a gastric ulcer
Miscellaneous
Hemobilia	+	+	+	–	+	–	–	–	History of: Cholecystectomy Endoscopic biliary biopsies or stenting TIPS placement Angioembolization Blunt or penetrating abdominal trauma Gallstones Cholecystitis Hepatic or bile duct tumors Intrahepatic stents Hepatic artery aneurysms Hepatic abscesses	Blood or clot emanating from the ampulla. ERCP may reveal a filling defect in the bile duct
Hemosuccus pancreaticus	+	+	+	–	+	–	+	–	Chronic pancreatitis Pancreatic pseudocysts Pancreatic tumors Pancreatic pseudoaneurysm Therapeutic endoscopy of the pancreas or pancreatic duct: Pancreatic stone removal Pancreatic duct sphincterotomy Pseudocyst drainage Pancreatic duct stenting	Blood or clot emanating from the ampulla. Cross-sectional imaging or angiography is often required to confirm the diagnosis.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Gastroesophageal varices are present in approximately 50,000 per 100,000 patients with cirrhosis, depending upon the clinical stage of the disease. The annual incidence of gastrointestinal varices ranges from a low of 7,000 per 100,000 individuals to a high of 8,000 per 100,000 individuals. Variceal hemorrhage occurs at a rate of around 10%-15% per year and depends on the severity of liver disease, size of varices, and presence of red wale marks (areas of thinning of the variceal wall).

• Gastroesophageal varices are present in approximately 50,000 per 100,000 patients with cirrhosis, depending upon the clinical stage of the disease^[1]
• In patients with compensated cirrhosis, gastroesophageal varices are present in 30,000 – 40,000 patients per 100,000 patients, whereas they can be present in up to 85,000 per 100,000 patients with decompensated cirrhosis^[2]

• The annual incidence of gastrointestinal varices ranges from a low of 7,000 per 100,000 individuals to a high of 8,000 per 100,000 individuals^[3]
• Progression from small varices to large varices occurs at a rate of 10%- 12% annually^[4]
• Variceal hemorrhage occurs at a rate of around 10%-15% per year and depends on the severity of liver disease, size of varices, and presence of red wale marks (areas of thinning of the variceal wall)^[5][6]

• African Americans are significantly more likely to be older than Caucasians or Hispanics, when patients with cirrhosis are studied^[7]
• White patients have equal proportions of cirrhotics in the younger and older age groups^[8]

• Hispanic and White patients were more likely to have cirrhosis due to alcohol than African American patients^[9]
• The prevalence of HCV appears to be the greatest in African American patients, compared to all other ethnic groups in the United States^[10]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

The most potent risk factor for the development of gastrointestinal varices is increased portal venous pressure. Conditions that predispose an individual to development of increased portal venous pressure and consequently leading to varices can be divided into three. Those leading to development of varices, those involved in progression of varices from small to large size and those leading to variceal hemorrhage.

The following are the common risk factors that lead to gastrointestinal varices:^[1]

• High hepatic venous portal gradient (HPVG > 10 mm Hg)

• Decompensated varices
• Alcoholic cirrhosis
• Red sign of endoscopy (dilated vessels on the surface of varices)

• Large varices ( > 5 mm)
• Red sign
• High MELD score
• HVPG > 16 mmHg
• Coagulopathy

• Thrombocytopenia
• Increasing bilirubin
• Increased international normalized ratio (INR)
• Red marks on the varices
• Severe cirrhosis or liver failure
• Continued alcohol use

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Screening esophagogastroduodenoscopy (EGD) for the diagnosis of esophageal and gastric varices is recommended after the diagnosis of cirrhosis is made.

Screening esophagogastroduodenoscopy (EGD) for the diagnosis of esophageal and gastric varices is recommended after the diagnosis of cirrhosis is made.^[1][2][3]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

If untreated, recurrent variceal hemorrhage occurs in 60% of patients, usually within 1-2 years of the initial hemorrhage. Gastrointestinal varices are an indication of increased portal venous pressure, especially in cirrhotic patients. The progressive increase in portal pressure leads to a progressive increase in size of the varices and an increased vascular wall tension. Variceal hemorrhage resulting from rupture occurs when the expanding force exceeds the maximal wall tension. Complications include, transient dysphagia, chest pain, esophageal ulceration, ulcerogenic bleeding, post-therapeutic hemorrhage, esophageal strictures, pleural effusions, pericarditis and portal vein thrombosis. Factors associated with a poor prognosis of presence of bacterial infections, HVPG >20 mm Hg, alcohol intake and obesity. The AIMS65 score is the best predictor of mortality in patients with variceal bleeding.

If untreated, recurrent variceal hemorrhage occurs in 60% of patients, usually within 1-2 years of the initial hemorrhage.^[1] Gastrointestinal varices are an indication of increased portal venous pressure, especially in cirrhotic patients. The progressive increase in portal pressure leads to a progressive increase in size of the varices and an increased vascular wall tension. Variceal hemorrhage resulting from rupture occurs when the expanding force exceeds the maximal wall tension. The following sequence of events typically summarizes the natural history of gastrointestinal varices:

• Early stages of chronic liver disease, where the hepatic venous portal pressure gradient (HPVG) is less than 10mmHg (normal)

• Middle to late stages of chronic liver disease, where the hepatic venous portal pressure gradient (HPVG) is greater than equal to 10mmHg
• Development rate is 8 % per year

• The size increases with progression of cirrhosis and due to hyperdynamic circulation
• Progression from small to large varices is 8 % per year^[2]

• Intravascular pressure in varices greater than the variceal wall tension leads to variceal rupture
• Rate of rupture of esophageal varices is 5 – 15 % per year
• Rate of rupture of gastric varices is 25 % (greater in IGV1 and GOV2)^[3]

• Persistent increase in portal pressure leads to recurrence after treatment if the underlying cause is not addressed

The following factors are associated with progression from small to large varices, at the time of baseline endoscopy:^[4][5]

• Severe cirrhosis (Child-Pugh class B and C)
• Alcoholic cirrhosis
• Presence of red wale marks (defined as longitudinal dilated venules resembling whip marks on the variceal surface)

Child-Pugh Classification of the Severity of Cirrhosis

Clinical feature/laboratory finding	Points*
	1	2	3
Encephalopathy	None	Grade 1–2    (or precipitant-induced)	Grade 3–4    (chronic)
Ascites	None	Mild/Moderate    (diuretic-responsive)	Tense    (diuretic-refractory)
Bilirubin (mg/dL)	<2	2–3	>3
Albumin (g/dL)	>3.5	2.3–3.5	<2.8
Prothrombin time or international normalized ratio (INR)	<4	4–6	>6
	<1.7	1.7–2.3	>2.3

Interpretation of Child-Pugh score

 5–6 points: Child A

7–9 points: Child B

10–15 points: Child C

Gastrointestinal varices may be complicated by the following:

• Variceal hemorrhage
• Post-sclerotherapy complications:^[6][7][8]
  • Transient dysphagia
  • Chest pain
  • Esophageal ulceration
  • Ulcerogenic bleeding
  • Post-therapeutic hemorrhage
  • Esophageal strictures
  • Pleural effusions
  • Pericarditis
  • Portal vein thrombosis

Six-week mortality is used as a predictor of prognosis for variceal hemorrhage^[9] The six-week mortality for variceal hemorrhage ranges from a low of 15% to a high of 25%^[10][11]

• Factors associated with a poor prognosis include:^{[12][13][14][15][16][17]}
  • Presence of bacterial infections
  • HVPG >20 mm Hg
  • Alcohol intake
  • Obesity

The AIMS65 score is best predictor of mortality in patients with variceal bleeding. The score is calculated as follows:

Variable	Score
Albumin	1
INR	1
Systolic blood pressure	1
Altered mental status	1
Age > 65 years	1

Score 0 = No risk

Score 1-2 = Moderate risk

Score > 2 = High risk