Gastroesophageal Varices

7 Interesting Facts of Gastroesophageal Varices 

1. Gastroesophageal varices are major venous collaterals between the portal venous system and systemic venous system located superficially on the distal esophagus and/or stomach; they form when clinically significant portal hypertension develops, most commonly owing to hepatic cirrhosis
2. All patients with cirrhosis should undergo screening esophagogastroduodenoscopy at diagnosis to identify the presence of varices; if varices with high-risk characteristics are identified, bleeding prophylaxis with either medical therapy (nonselective β-blocker) or endoscopic therapy (variceal ligation accomplished with repeated endoscopies) is recommended
3. Varices themselves are often asymptomatic until they bleed, in which case they present with hematemesis and potentially life-threatening blood loss
4. Management of an acute variceal hemorrhage requires resuscitation using a restrictive transfusion strategy (transfuse when hemoglobin is 7 g/dL and maintain at 7-8 g/dL), administration of a vasoactive agent (usually octreotide), and endoscopic variceal ligation; bleeding from varices that extend into (or are located entirely within) the stomach may require alternative interventions 
5. After an acute variceal hemorrhage, secondary bleeding prophylaxis (with nonselective β-blockers plus repeated endoscopic variceal ligation of all remaining varices) is recommended
6. Transjugular intrahepatic portosystemic shunt is usually the treatment of choice after failure of combination treatment with nonselective β-blockers plus endoscopic variceal ligation
7. 6-week mortality is 15% to 25% after an acute variceal hemorrhage; 5-year mortality is 20% when variceal hemorrhage (as an isolated decompensating event) heralds decompensated cirrhosis; 5-year mortality is more than 80% when variceal hemorrhage occurs in the setting of preexisting ascites and/or encephalopathy 

Pitfalls

• Do not use fixed dosing for nonselective β-blockers for primary or secondary prevention of variceal hemorrhage; drug effect may be optimized, and risk of hemorrhage lowered, by upward dose titration to the desired hemodynamic response 
• Data are lacking to support correction of coagulopathy with fresh frozen plasma or factor VIIa in the setting of acute variceal hemorrhage. There is risk of volume overload and transfusion-related reactions without clear benefit 
• In patients with refractory ascites or spontaneous bacterial peritonitis, avoid high doses of nonselective β-blockers; reduce dose or discontinue if there are signs of severe circulatory dysfunction (eg, systolic blood pressure below 90 mm Hg, serum sodium level below 130 mEq/L, unexplained deterioration in renal function) 

• Gastroesophageal varices are major venous collaterals between the portal venous system and systemic venous system located superficially on the distal esophagus and/or stomach
  • Formed when clinically significant portal hypertension develops, most commonly owing to hepatic cirrhosis
• Varices begin to develop as portal pressure becomes elevated above 10 mm Hg; these vessels slowly enlarge and may eventually rupture when portal pressure exceeds 12 mm Hg 
  • Presents as an acute upper gastrointestinal hemorrhage, which may be life-threatening
• Variceal hemorrhage is one of several defining decompensatory events in hepatic cirrhosis (others include onset of ascites and/or hepatic encephalopathy) and is associated with greatly increased mortality risk (15%-25% within 6 weeks) 

Classification of Gastroesophageal Varices

• Several classification systems are relevant to the diagnosis and management of gastroesophageal varices
  • Classification of varices by anatomic location 
    • Esophageal varices
    • Gastric varices (present in 20% of patients with cirrhosis) 
      • Sarin classification
        • Cardiofundal varices
          • Gastroesophageal varices type 1 (most common): extending from distal esophagus to below the gastric cardia into the lesser curvature
          • Gastroesophageal varices type 2: extending from distal esophagus into the gastric fundus
          • Isolated gastric varices type 1: located in the gastric fundus
        • Varices located elsewhere in the stomach
          • Isolated gastric varices type 2 (extremely uncommon)
  • Classification of hepatic cirrhosis (Related: Hepatic Cirrhosis)
    • By presence or absence of decompensation
      • Compensated cirrhosis: cirrhosis without complications; patient has not yet developed ascites or other associated complications 
      • Decompensated cirrhosis: portal hypertension and decreased hepatocellular synthetic dysfunction have caused 1 or more of the following complications: 
        • Ascites
          • Most common of these complications; its appearance is an important marker of rapid deterioration and increased mortality for patients with cirrhosis
        • Variceal bleeding
        • Hepatic encephalopathy
        • Nonobstructive jaundice is also sometimes considered a decompensating event
        • Additional complications may develop after the onset of ascites (eg, hepatorenal syndrome, hepatopulmonary syndrome, spontaneous bacterial peritonitis)
    • By prognostic stage
      • Child-Pugh score classifies patients into 3 stages (also known as Child-Turcotte-Pugh score/class)
        • Child-Pugh class A corresponds to compensated cirrhosis; patients with Child-Pugh class B/C are mostly decompensated 
        • Based on sum of scores: bilirubin and albumin levels, INR, and the presence and severity of ascites and encephalopathy 
          • Class A: 5 to 6 points
          • Class B: 7 to 9 points
          • Class C: 10 to 15 points
          • Points are assigned as follows:
            • Bilirubin level
              • Less than 2 mg/dL: 1 point
              • 2 to 3 mg/dL: 2 points
              • Greater than 3 mg/dL: 3 points
            • Albumin level
              • Greater than 3.5 g/dL: 1 point
              • 2.8 to 3.5 g/dL: 2 points
              • Less than 2.8 g/dL: 3 points
            • INR
              • Less than 1.7: 1 point
              • 1.7 to 2.3: 2 points
              • Greater than 2.3: 3 points
            • Ascites
              • None: 1 point
              • Mild: 2 points
              • Severe: 3 points
            • Hepatic encephalopathy
              • None: 1 point
              • Stage 1 to 2: 2 points
              • Stage 3 to 4: 3 points

Clinical Presentation

History

• Varices themselves are often asymptomatic until they bleed
  • Hematemesis can range from minor to massive and life-threatening
  • Melena may occur
  • Typically there is no chest or abdominal pain associated with bleeding
• Patients may complain of dyspnea associated with anemia and/or lightheadedness (especially on standing) resulting from hypotension secondary to variceal hemorrhage; the latter may result in loss of consciousness and collapse

Physical examination

• Physical signs may be absent until acute bleeding occurs in patients whose varices are due to prehepatic portal hypertension
• In patients with cirrhosis and those with posthepatic portal hypertension, there are often signs of chronic liver disease, including:
  • Jaundice
  • Palmar erythema, clubbing, and silver-white proximal nail plates (Terry nails), most commonly involving thumb and index finger
  • Scratch marks due to pruritus, bruising from impaired clotting function, and spider angiomas on the torso
  • Distended abdomen due to ascites and/or hepatosplenomegaly
  • Gynecomastia and testicular atrophy in men
  • With low-grade hepatic encephalopathy: lethargy or confusion
  • With higher-grade encephalopathy: muscle rigidity, asterixis, clonus, and eventually coma
• Splenomegaly and dilated veins in the abdominal wall that show downward flow away from the umbilicus (caput medusae) are suggestive of portal hypertension
• With an acute variceal hemorrhage:
  • Depending on degree of blood loss, tachycardia and hypotension may be present
  • Patient may be actively vomiting bright red blood or have coffee-ground emesis
  • Melena/heme-positive stool result on rectal examination

Causes and Risk Factors

Causes

• In adults, portal hypertension due to hepatic cirrhosis is the most common cause; cirrhosis results in hepatic sinusoidal obstruction from these processes:
  • Viral cirrhosis (chronic hepatitis B or C)
  • Alcoholic cirrhosis
  • Nonalcoholic fatty liver disease
• Less commonly, noncirrhotic portal hypertension is the cause of gastroesophageal varices
  • Prehepatic obstruction
    • Portal vein thrombosis
    • Splenic vein thrombosis
    • Mesenteric vein thrombosis
  • Intrahepatic, presinusoidal obstruction
    • Schistosomiasis (becomes sinusoidal in more advanced stages)
    • Biliary cirrhosis
  • Posthepatic obstruction
    • Budd-Chiari syndrome (hepatic vein obstruction)
    • Inferior vena cava obstruction
    • Right-sided heart failure
    • Restrictive pericarditis
• In children, portal hypertension due to portal vein thrombosis or secondary biliary cirrhosis (from biliary atresia) is the most common cause of gastroesophageal varices

Risk factors and/or associations

Other risk factors/associations

• For presence of varices:
  • Compensated cirrhosis: varices are present in 30% to 40% of patients with clinically significant portal hypertension 
  • Decompensated cirrhosis: varices present in up to 85% of patients 
• For variceal hemorrhage: 
  • More advanced stages of cirrhosis
  • Larger varices (greater than 5 mm diameter) 
  • Presence of red wale marks (areas of thinning of the variceal wall) noted endoscopically

Diagnostic Procedures

Primary diagnostic tools

• For patient presenting with active hematemesis or suspected upper gastrointestinal bleeding: 
  • Perform urgent laboratory testing to assess and manage blood loss, coagulopathy, and hydration status, and to evaluate liver function
  • Perform endoscopy as soon as patient is stable (and within 12 hours of presentation) to determine bleeding source
    • Infusion of the vasoactive drug octreotide, and administration of prophylactic antibiotic is indicated after fluid resuscitation
    • If there is active hematemesis, intubate the patient to protect the airway
• For stable patient with cirrhosis, determine if varices are present and if they are at high risk for hemorrhage
  • Perform screening esophagogastroduodenoscopy at the time of cirrhosis diagnosis in all patients 
  • Although not widely accepted for this purpose, noninvasive testing may be able to identify patients with low probability of high-risk varices, obviating the need for screening esophagogastroduodenoscopy at cirrhosis diagnosis 
    • Noninvasive strategies include: 
      • Combination of liver stiffness on ultrasonic elastography plus platelet count: when liver stiffness is less than 20 kPa and platelet count is above 150,000 cells/mm³, there is a very low probability (below 5%) of having high-risk varices 
      • Platelet count to spleen length ratio may identify patients with liver disease who are at high risk of having esophageal varices, but it does not accurately identify varices at high risk of bleeding that require primary prophylaxis 
      • Spleen stiffness measured by ultrasonic elastography 
  • Risk for variceal hemorrhage is high in the presence of any of the following: 
    • Decompensated cirrhosis
    • Larger varices (greater than 5 mm diameter) 
    • Presence of red wale marks (areas of thinning of the variceal wall) noted endoscopically

Laboratory

• For patient presenting with hematemesis:
  • CBC
  • Prothrombin time/INR and partial thromboplastin time
  • Blood typing and crossmatch
  • Electrolyte, glucose, BUN, and creatinine levels
  • Liver function tests: ALT, AST, alkaline phosphatase, γ-glutamyltransferase, bilirubin, and albumin levels
• For noninvasive assessment of probability of high-risk varices (in combination with transient elastography):
  • Platelet count
    • Used in combination with results of transient elastography to noninvasively predict low likelihood of high-risk varices 
    • Liver stiffness less than 20 kPa and platelet count above 150,000 cells/mm³ confer a very low probability (below 5%) of having high-risk varices 

Imaging

• Imaging elastography
  • Detects hepatic fibrosis and provides an estimate of the stage of cirrhosis using liver stiffness as a proxy; it is recommended by the American Gastroenterological Association over other noninvasive means (eg, blood tests) to assess for fibrotic changes 
    • Ultrasonographic elastography (transient elastography or acoustic radiation force impulse)
      • Uses physical or acoustic force applied externally over the liver to produce shear waves in liver tissue
      • Fibrosis alters elastic properties of hepatic tissue, which are measured by ultrasonography
      • Transient elastography is the most extensively studied technique 
      • Acoustic radiation force impulse elastography (also known as shear wave elastography) may be more reliable in patients who are obese or have ascites
    • Magnetic resonance elastography
      • MRI-based technique has higher sensitivity and accuracy than transient elastography 
      • May be more appropriate for obese patients, and allows sampling of a much larger section of the liver
  • Either acoustic radiation force impulse (shear wave) elastography or magnetic resonance elastography are preferred for initial diagnosis and staging of hepatic fibrosis 
  • Elastography can be used in combination with results of platelet count to predict low likelihood of high-risk varices 
    • Liver stiffness below 20 kPa and platelet count greater than 150,000 cells/mm³ confer a very low probability (less than 5%) of having high-risk varices
      • In these patients, it may be reasonable to omit screening endoscopy
      • Noninvasive testing is not sensitive enough to rule out the presence of all varices, but it is sensitive enough to rule out high-risk varices
      • Data behind this noninvasive testing recommendation are primarily obtained from patients with cirrhosis due to untreated viral hepatitis

Procedures

• Esophagogastroduodenoscopy involves passage of an upper gastrointestinal endoscope to allow visualization and/or biopsy of the distal esophagus and gastric area (and duodenum if source of bleeding is not evident), with or without adjunctive delivery of ligating bands if varices are detected
• Acute upper gastrointestinal bleeding
• Screening tool in all patients with cirrhosis to determine presence and size of esophageal varices
• Risk of aspiration pneumonia, especially in a patient with hematemesis who is actively vomiting; consider protecting the airway first by elective endotracheal intubation
• Risk of esophageal perforation (very rare)
• Endoscopic evidence of variceal bleeding includes: 
  • Active bleeding visualized from a varix
  • “White nipple sign” overlying a varix
  • Clots overlying a varix
  • Varices with no other potential source of bleeding

Other diagnostic tools

• Hepatic venous pressure gradient
  • Difference obtained by directly measuring the free hepatic venous pressure and by obtaining a wedged hepatic venous pressure measurement via an occlusion balloon
  • Hepatic venous pressure gradient = wedged hepatic venous pressure − free hepatic venous pressure 
    • Reference range: 3 to 5 mm Hg
    • Mild portal hypertension: above 5 but below 10 mm Hg
    • Clinically significant portal hypertension: 10 mm Hg or above
    • Variceal bleeding tends to occur when gradient is greater than 12 mm Hg
    • When exceeding 20 mm Hg, risk of variceal hemorrhage is very high
• Ratio of platelet count to spleen length (as assessed by abdominal ultrasonography)
  • Ratio of platelet count to spleen length (in mm) above 909: (cells/mm³)/mm 
    • Presence of esophageal varices of any size can be excluded (would miss only 7% of adults with varices of any size)
  • Increased spleen length in patients with chronic liver disease is generally caused by increased portal pressure; spleen length increases with increasing portal pressure
  • Thrombocytopenia is caused by splenic pooling in portal hypertension, immune-mediated mechanisms, or decreased synthesis of thrombopoietin; with portal hypertension, platelet count decreases with increasing portal pressure

Differential Diagnosis

Most common

• Upper gastrointestinal bleeding from nonvariceal source
  • In the presence of advanced hepatic disease, evidence of portal hypertension, or prior known variceal hemorrhage, upper gastrointestinal bleeding is likely due to variceal hemorrhage; other sources of upper gastrointestinal bleeding in this same population include:
    • Portal hypertensive gastropathy
      • Mucosal and submucosal vascular ectasia caused by portal hypertension
      • 20% to 80% prevalence in patients with hepatic cirrhosis 
      • Responsible for 2% to 12% of acute gastrointestinal bleeding in cirrhosis; more commonly presents as chronic iron deficiency anemia 
      • Endoscopy will usually differentiate from bleeding varices; typically appears as a snakeskin-like mosaic pattern in the gastric fundus or as flat or raised red or brown spots in more advanced stages
      • Initial medical management of acute bleeding from portal hypertensive gastropathy is the same as for esophageal varices; endoscopic management may be successful
    • Gastric antral vascular ectasia
      • Occurs in small percentage of patients with decompensated cirrhosis
      • Acute bleeding is uncommon (responsible for 4% of upper gastrointestinal bleeds in patients with or without cirrhosis); more commonly presents as chronic iron deficiency anemia due to ongoing low-level blood loss 
      • Endoscopy will differentiate from bleeding varices
        • “Watermelon stomach”: reddish spots arranged in stripes projecting proximally and radially from pylorus, or
        • “Honeycomb stomach”: reddish spots arranged in honeycomb or nodular pattern mainly in antrum of stomach
      • Initial medical management of acute bleeding from gastric antral vascular ectasia is the same as for esophageal varices; endoscopic thermoablation (argon-plasma coagulation) is often used
    • Peptic ulcer disease (Related: Peptic Ulcer Disease)
      • Produces ulcerations in stomach or duodenum owing to an imbalance between mucosal protective factors and various mucosa-damaging mechanisms
      • Helicobacter pylori infection and/or NSAID use are found in most patients with duodenal and gastric ulcers
      • Classic ulcer-related pain is epigastric or retrosternal; described as gnawing, burning discomfort (dyspepsia) that is relieved by intake of certain foods or liquids (eg, ice cream, milk) or antacids
      • Upper endoscopy is the diagnostic/therapeutic test of choice for acute upper gastrointestinal bleeding due to peptic ulcer
• Upper gastrointestinal bleeding in the setting of recently performed endoscopic variceal ligation
  • In this setting, risk of bleeding from recurrent varix was 3.9% in recent retrospective study 
  • Bleeding from ligation-induced ulcers happened in 3.6% of ligation sessions 
    • Lower rate after elective banding procedures (0.5%) 
    • Higher rate after banding done to treat acute hemorrhage (7.1%) 
    • Timing of bleeding (most commonly within 11 days after banding procedure) may suggest the diagnosis 
  • Upper endoscopy will confirm source of bleeding
• Varices as a manifestation of noncirrhotic portal hypertension
  • Portal vein thrombosis
    • Defined as partial or complete obstruction of the portal, splenic, or mesenteric vein lumen by a clot, or substitution by neoformed tortuous vessels called cavernomas 
    • In patients without cirrhosis, the term extrahepatic portal vein obstruction should be used because it does not include isolated splenic vein or mesenteric vein thrombosis
    • Risk factors in adults (in addition to cirrhosis) include neoplasms, thrombophilic conditions, and abdominal surgery/inflammatory conditions
    • Risk factors in children include umbilical vein catheterization, coagulopathy, neonatal sepsis, abdominal infection/surgery, and cardiovascular malformations
    • Suspect if the patient has no risk factors for hepatic cirrhosis
    • Variceal bleeding without abdominal pain is the first manifestation of portal vein obstruction in 11% to 17% of patients; ascites is often present 
    • Initial diagnostic test is abdominal ultrasonography, with accuracy of 88% to 98%; less sensitive in incomplete obstruction; cross-sectional imaging is necessary to evaluate extent of clot 
  • Noncirrhotic portal fibrosis (also called idiopathic portal hypertension, hepatoportal sclerosis, and obliterative venopathy)
    • Disorder of unknown cause; may be due to early or recurrent infection and/or prothrombotic state
    • In developing countries, most common in young males in third to fourth decades of life 
    • Variant form affects females more commonly and presents around fifth decade of life 
    • Clinically, patients have moderate to massive splenomegaly with or without hypersplenism, preserved liver function, and patent hepatic and portal veins on imaging
    • Endoscopically, varices are seen in more than 90% of patients 
    • Variceal bleeding occurs in up to 84% of patients studied 
  • Schistosomiasis
    • Portal hypertension can be a result of intestinal infection with Schistosoma japonicum, Schistosoma mansoni, or Schistosoma mekongi
      • Initially causes presinusoidal fibrosis; with long-term infection, causes sinusoidal fibrosis
    • Common cause of portal hypertension and variceal bleeding in Africa, Asia, South America, and the Middle East
    • Suspect in a patient with gradual development of hepatomegaly and splenomegaly (often over a period of many years) without hepatic dysfunction in a resident or visitor to endemic areas; variceal bleeding may occur in the absence of ascites
    • Diagnosis is with demonstration of ova in stool and abdominal ultrasonogram demonstrating periportal fibrosis

Treatment Goals

• In patients with compensated hepatic cirrhosis, prevent cirrhotic decompensation
  • This is the overarching goal as opposed to simply preventing varices or variceal hemorrhage
• In patients with endoscopically proven varices, prevent first variceal hemorrhage 
• In patients with acute variceal hemorrhage: 
  • Control current bleeding
  • Prevent early rebleeding (within the first 5 days)
  • Prevent recurrent bleeding (after 5 days is considered a new episode)

Disposition

Admission criteria

Criteria for ICU admission

• All patients with variceal hemorrhage

Recommendations for specialist referral

• Refer to a gastroenterologist and/or a hepatologist for:
  • Evaluation and management of cirrhosis
  • Diagnosis and treatment of variceal hemorrhage
  • Ongoing monitoring of varices
• In some settings (eg, rural), initial treatment of active hematemesis or suspected upper gastrointestinal bleeding is provided by the most experienced endoscopist available, which may be a general surgeon or other appropriately trained physician

How is this treated?

Management of acute variceal hemorrhage

• Assess and maintain adequate circulatory status
  • Volume resuscitation with isotonic fluids to maintain hemodynamic stability without overloading the splanchnic venous system (which would worsen portal hypertension); aim for systolic blood pressure of 70 to 100 mm Hg 
  • Use a restrictive transfusion policy; transfuse packed RBCs at a hemoglobin threshold of 7 g/dL and maintain it at 7 to 8 g/dL (associated with decreased mortality and lower rates of early rebleeding as compared with a more liberal transfusion policy) 
• Commence infusion of a vasoconstrictor (ie, somatostatin, vasopressin, or their respective analogues, octreotide and terlipressin) as soon as possible; octreotide is used in the United States
  • Meta-analysis showed significantly lower risk of acute all-cause mortality, decreased transfusion requirement, and shorter hospital stay; no difference in efficacy between terlipressin, somatostatin, and octreotide
  • Stop treatment after definitive hemostasis has been achieved or after 3 to 5 days 
• Correct coagulopathy or thrombocytopenia if present 
  • Use blood products sparingly owing to risk of transfusion-related circulatory overload and elevated portal pressure 
  • US guidelines do not recommend use of fresh frozen plasma or factor VIIa concentrate as part of management of variceal bleeding 
  • British guidelines recommend clotting factor support when INR exceeds 1.5 times upper reference limit; however, other organizations do not support the use of INR as an indicator of coagulopathy in cirrhotic patients 
  • There are no guidelines specifically for the use of platelet transfusion in variceal hemorrhage; platelet support is commonly given when count is below 50,000 cells/mm³ and there is active bleeding 
• Initiate prophylactic antibiotics
  • IV ceftriaxone 1 g every 24 hours (unless otherwise contraindicated) is the antibiotic of choice for decompensated cirrhosis 
  • Continue for a maximum of 7 days (consider discontinuing when hemorrhage has resolved and vasoactive drugs are discontinued) 
• Proceed to endoscopy when patient is stable after fluid resuscitation and initiation of pharmacologic therapies (within 12 hours of presentation) 
  • If there is aspiration risk (eg, obtunded patient, vomiting, brisk bleeding), endotracheal intubation is indicated to protect airway
  • If esophageal varices are detected on endoscopy, treat with endoscopic variceal ligation or sclerotherapy 
  • If gastric varices are detected (occur in 20% of patients with cirrhosis), treatment may be endoscopic or endovascular depending on anatomic location 
    • Varices extending from esophagus into the lesser curvature (gastroesophageal varices type 1) may be treated with endoscopic techniques (eg, sclerotherapy, band ligation, cyanoacrylate glue injection, coil insertion)
      • Sclerotherapy and band ligation are less effective for esophageal varices 
    • Cardiofundal varices are usually not amenable to endoscopic therapy and are treated with interventional radiology techniques (eg, balloon-occluded retrograde transvenous obliteration, transjugular intrahepatic portosystemic shunt) 
      • Either transvenous obliteration or transjugular intrahepatic portosystemic shunt has been regarded as the treatment of choice; however, there is evidence that balloon-occluded retrograde transvenous obliteration is associated with lower rates of rebleeding and mortality 
    • There is a high risk of rebleeding after treatment of gastric variceal hemorrhage 
  • Bridge therapy may be necessary to control ongoing hemorrhage until more definitive therapy with transjugular intrahepatic portosystemic shunt is possible 
    • Gastroesophageal balloon tamponade is an option
    • Insertion of a self-expanding metal esophageal stent may be a viable alternative 
• Consider transjugular intrahepatic portosystemic shunt or surgical venous shunting if bleeding continues or recurs 
• Although rarely used for this purpose, if endoscopy is unavailable and the physician has experience in insertion, a gastroesophageal balloon tube (eg, Sengstaken-Blakemore tube, Minnesota tube) can be used as an initial temporizing method to stanch brisk bleeding

Secondary prevention of variceal hemorrhage (ongoing treatment after initial treatment of acute hemorrhage) 

• For patients at high risk of rebleeding, consider early transjugular intrahepatic portosystemic shunt placement (within first 72 hours of endoscopic variceal ligation) to decompress the portal vein 
  • High-risk patients
    • Hepatic venous pressure gradient exceeds 20 mm Hg (if measured) 
    • Child-Pugh class C cirrhosis (with score of 10-13) 
    • Child-Pugh class B cirrhosis with active bleeding on endoscopy despite IV vasoactive drug therapy 
    • Patients who have experienced variceal bleeding while already on primary prophylaxis with nonselective β-blocker or who have already had prophylactic variceal eradication with endoscopic variceal ligation 
• For patients not at high risk, combination of ongoing endoscopic variceal ligation procedures (repeated every 1-4 weeks until eradication) plus nonselective β-blocker is recommended 
  • Meta-analysis demonstrated that combination therapy is significantly more effective than endoscopic variceal ligation alone in preventing all-source gastrointestinal hemorrhage 
  • Continue indefinite treatment with nonselective β-blockers (eg, propranolol, nadolol, carvedilol) 
  • Perform endoscopic variceal ligation every 1 to 4 weeks until varices are eradicated 
  • Transjugular intrahepatic portosystemic shunt is the treatment of choice after failure of combination treatment with nonselective β-blockers plus endoscopic variceal ligation 

Nonacute management of gastroesophageal varices

• Goal is to prevent decompensation and prevent first variceal hemorrhage in those at high risk of bleeding 
  • Endoscopically proven varices 
    • Nonselective β-blocker prophylaxis and endoscopic ligation are considered equally effective in preventing first variceal bleed in patients with high-risk esophageal varices (eg, moderate to large varices [greater than 5 mm], smaller varices with high-risk endoscopic features [red wale marks]) or decompensated cirrhosis 
      • Nonselective β-blockers
        • May also prevent progression to decompensated cirrhosis by preventing ascites as well as variceal bleeding 
        • Propranolol, nadolol, or carvedilol may be used 
        • Rather than using a fixed dose, drug effect may be optimized, and risk of hemorrhage lowered, by upward dose titration to the desired hemodynamic response 
        • Carvedilol has additional α₁-blocking effect and is more effective at reducing portal pressure; however, it has not been shown to be superior to conventional nonselective β-blockers 
      • Endoscopic variceal ligation 
        • Such ligation performed every 2 to 8 weeks until varices are eradicated is an option for primary prevention of variceal bleeding if moderate to large varices (greater than 5 mm) are present or if smaller varices with high-risk endoscopic features are present
        • After endoscopic variceal ligation for primary prophylaxis, repeat endoscopy with endoscopic variceal ligation every 1 to 8 weeks until variceal obliteration can be documented
      • Select treatment according to individual patient characteristics and preference
        • Nonselective β-blocker prophylaxis is preferred for small high-risk varices, because they are less amenable to endoscopic treatment 
        • Combination therapy (medical plus interventional) is not recommended
    • Nonselective β-blocker prophylaxis is not recommended for small (less than 5 mm) esophageal varices with low risk of bleeding
      • There is conflicting evidence on role of β-blockers in preventing small varices from growing larger 
    • A similar approach may be considered for gastric varices 
      • Type 1 gastroesophageal varices (most common) are treated as for esophageal varices 
      • Type 2 gastroesophageal varices and isolated gastric varices are preferentially treated with nonselective β-blocker prophylaxis 
  • In patients with cirrhosis but without varices on endoscopy 
    • There is no evidence for treatment with nonselective β-blockers to prevent formation of varices 
    • Prevent progression to clinically significant portal hypertension by treating underlying cause of cirrhosis and preventing further hepatic injury 

Drug therapy

• Vasoactive agent for acute variceal hemorrhage
  • Octreotide
    • Octreotide Acetate Solution for injection; Adults: 50 mcg IV followed by 50 mcg/hour continuous IV infusion for 2 to 5 days. May repeat bolus dose in first hour if ongoing bleeding.
• Antibiotic prophylaxis during acute variceal hemorrhage
  • Ceftriaxone
    • Ceftriaxone Sodium Solution for injection; Adults: 1 g IV every 12 to 24 hours for 2 to 7 days beginning immediately after endoscopy has been studied and may be more effective than norfloxacin.
• Nonselective β-blocker for primary and/or secondary prophylaxis of variceal hemorrhage
  • Drugs with both β₁- and β₂-adrenergic blockade are necessary for additive mechanistic effect on portal blood flow
    • Propranolol
      • Propranolol Hydrochloride Oral tablet; Adults: 20 to 40 mg PO twice a day. Adjust every 2 to 3 days until treatment goal is achieved (Resting heart rate of 55 to 60 beats per minute while maintaining systolic blood pressure at 90 mm Hg or above). Max daily dose: 320 mg/day in patients without ascites; 160 mg/day in patients with ascites. 
    • Nadolol
      • Nadolol Oral tablet; Adults: 20 to 40 mg PO once daily. Adjust every 2 to 3 days until treatment goal is achieved (Resting heart rate of 55-60 beats per minute while maintaining systolic blood pressure at 90 mm Hg or above). Max daily dose: 160 mg/day in patients without ascites; 80 mg/day in patients with ascites. 
    • Carvedilol (combined α₁- and nonselective β-adrenergic blocker)
      • Carvedilol Oral tablet; Adults: Initially, 6.25 mg PO once daily. After 3 days increase to 6.25 mg PO twice daily, maintaining systolic arterial pressure above 90 mm Hg. Max dose: 12.5 mg/day (except in patients with persistent arterial hypertension). 

Nondrug and supportive care

In patients with cirrhosis, advise weight loss if obesity is present and advise complete abstinence from alcohol; these actions may moderate worsening of portal pressure 

Procedures

Endoscopic variceal ligation

General explanation

• Using a standard endoscope with a ligating device, visualized varices are captured and banded, causing occlusion and eventual thrombosis and necrosis
• Requires multiple endoscopic procedures to eradicate all varices

Indication

• Treatment of choice for controlling esophageal variceal hemorrhage 
• Primary bleeding prophylaxis for medium to large (greater than 5 mm) endoscopically detected varices 
• Superior to endoscopic sclerotherapy for all major outcomes

Complications

• Postprocedural chest discomfort may occur
• Banding ulcer hemorrhage (ulceration on varix that was previously treated with endoscopic variceal ligation) occurs in up to 3.6% of patients, most commonly within the first 11 days 

Gastroesophageal balloon tamponade tube

General explanation

• Sengstaken-Blakemore tube has 3 lumens: gastric balloon, esophageal balloon, and gastric aspiration
• Minnesota tube has 4 lumens: gastric balloon, esophageal balloon, gastric aspiration, and an esophageal aspiration port
• Tube is passed, usually through the mouth, into the esophagus and stomach, then balloons are inflated and pressure is applied with traction
  • Pressure delivered is monitored with manometry; ongoing bleeding is monitored by assessing aspirate
• Must be closely monitored within the emergency department or ICU
• Endotracheal intubation and sedation are often required

Indication

• Endoscopy is unavailable for a patient with portal hypertension or prior variceal hemorrhage who has severe ongoing upper gastrointestinal bleeding that does not resolve with pharmacologic therapy
• When endoscopy is available, the indication for a gastroesophageal balloon tamponade tube is substantial ongoing variceal hemorrhage that cannot be controlled with endoscopic interventions

Contraindications

• If endoscopy is available, gastroesophageal balloon tamponade tube should not be used as initial treatment
• Cannot be used for more than 24 hours 

Complications

• Adverse events may be severe and include mucosal ulceration and necrosis, esophageal perforation and rupture, aspiration pneumonia, and airway obstruction
• Mortality rate approaches 20% 

Interpretation of results

• Provides hemostasis in up to 80% of patients 

Transjugular intrahepatic portosystemic shunt

General explanation

• Transjugular access to the infrahepatic inferior vena cava is obtained and an optimal hepatic vein (most often the right hepatic vein owing to its angle and diameter) is entered 
• Using imaging guidance, a puncture needle is passed from the hepatic vein to the intrahepatic portal vein and a shunt is created and dilated
• A bridging stent is left in place; covered stents (rather than bare metal stents) are preferred owing to higher patency rates

Indication

• Cardiofundal varices not amenable to endoscopic therapy at time of first variceal hemorrhage
• Gastroesophageal varices at high risk of rebleeding after initial episode
• Portal hypertension and recurrent variceal bleeding

Complications

• May worsen hepatic encephalopathy or cause other acute hepatic dysfunction
• Use of covered (as opposed to bare) stent may reduce the risk of hepatic encephalopathy 

Balloon-occluded retrograde transvenous obliteration 

General explanation

• Requires interventional radiologist skilled in the procedure
• Obliteration of gastric varix by instillation of sclerosants (or liquid embolic agent) delivered through a vascular catheter and aided by balloon occlusion to prevent dissemination of the agent out of the intended field

Indication

• Gastric varices (gastroesophageal varices type 2 and isolated gastric varices type 1)

Complications

• May result in increased portal venous blood flow with progression of esophageal varices in some patients
• Embolic phenomenon due to sclerosant
• Precipitation of hepatic decompensation

Comorbidities

• Most patients with gastroesophageal varices have underlying hepatic cirrhosis of various causes, which should be managed carefully according to stage of disease
  • Several relevant practice guidance documents make diagnostic and/or treatment recommendations for cirrhosis and its associated symptoms and conditions 
    • American Association for the Study of Liver Diseases 
    • American Association for the Study of Liver Diseases/American College of Gastroenterology
    • American Association for the Study of Liver Diseases/European Association for the Study of the Liver 
    • National Institute for Health and Care Excellence 
    • American Association for the Study of Liver Diseases/Infectious Diseases Society of America 
• In patients with refractory ascites or spontaneous bacterial peritonitis, avoid high doses of β-blockers and reduce dose or discontinue if there are signs of severe circulatory dysfunction (eg, systolic blood pressure below 90 mm Hg, serum sodium level below 130 mEq/L, unexplained deterioration in renal function) 
  • Consider restarting after correction of circulatory and renal status
• Alcohol use disorder is a common comorbidity; patient should be monitored for alcohol withdrawal symptoms and managed appropriately (Related: Alcohol Withdrawal)

Monitoring

• Compensated cirrhosis, without varices on screening esophagogastroduodenoscopy
  • If liver injury is ongoing (eg, patient with alcohol use disorder who is still drinking, active HCV infection) and/or cofactors of disease are present (eg, obesity), repeat surveillance endoscopy at 2-year intervals 
  • In the absence of ongoing injury, repeat at 3-year intervals 
  • No data to support discontinuing screening endoscopies if several of them do not show varices
• Compensated cirrhosis, with small varices on screening esophagogastroduodenoscopy; patient not receiving primary prophylaxis 
  • If liver injury is ongoing (eg, patient with alcohol use disorder who is still drinking, active HCV infection) and/or cofactors of disease are present (eg, obesity), repeat surveillance endoscopy at 1-year intervals
  • In the absence of ongoing injury, repeat at 2-year intervals
• Patients with varices receiving primary variceal hemorrhage prophylaxis with nonselective β-blockers or carvedilol 
  • Serial endoscopy monitoring not required 
• Patients treated with endoscopic variceal ligation for eradication of varices after variceal hemorrhage 
  • First esophagogastroduodenoscopy within 3 to 6 months after eradication and every 6 to 12 months thereafter
• Decompensated cirrhosis
  • For patients who progress from compensated to decompensated cirrhosis, repeat endoscopy when decompensation develops 

Complications

• Variceal hemorrhage, early rebleeding, and recurrent bleeding are common complications and may result in death
• Variceal hemorrhage increases risk of:
  • Hepatic encephalopathy
  • Spontaneous bacterial peritonitis
  • Hepatorenal syndrome

Prognosis

• After acute variceal hemorrhage, 6-week mortality is 15% to 25%
  • Factors associated with poor outcomes after hemorrhage:
    • Bacterial infection
    • Hepatic venous pressure gradient above 20 mm Hg 
    • If varices are untreated, hemorrhage will recur in 60% of patients within 1 to 2 years 
  • Outcomes of variceal hemorrhage are better in patients with noncirrhotic portal hypertension (owing to intact synthetic function)
• When variceal hemorrhage (as an isolated decompensating event) heralds decompensated cirrhosis, 5-year mortality is 20%. When it occurs in the setting of preexisting ascites and/or encephalopathy, 5-year mortality is above 80% 

Screening

At-risk populations

• Patients with hepatic cirrhosis

Screening tests

• Perform initial endoscopic screening for asymptomatic esophageal and gastric varices at time of cirrhosis diagnosis in all patients 
  • For patients with no varices on initial screening, repeat endoscopy every 2 to 3 years
  • For patients with small varices found on initial screening, repeat endoscopy every 1 to 2 years
  • For patients with high-risk features for progression to bleeding varices, perform yearly upper endoscopy (even if no varices are identified on initial examination); high-risk features include:
    • Cirrhosis caused by alcohol use
    • Decompensated cirrhosis
    • Small varices with high-risk appearance (characteristic red wale marks or spots)

Prevention

• In patients with cirrhosis, advise weight loss if obesity is present, and advise treatment of any chronic viral hepatitis and complete abstinence from alcohol; these interventions may moderate worsening of portal pressure and prevent development of varices
• In patients with cirrhosis but no varices on screening endoscopy, there is no evidence for treatment with nonselective β-blockers to prevent formation of varices 

References

1: Garcia-Tsao G et al: Portal hypertensive bleeding in cirrhosis: risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 65(1):310-35, 2017