Gastric Varices

Etiology

Gastric varices are commonly encountered in patients with cirrhosis because of portal hypertension. However, gastric varices can occur in patients with noncirrhotic portal hypertension and are considered distinct, with distinct etiology, pathophysiology, and treatment strategies compared with gastric varices secondary to cirrhosis-related portal hypertension.[6]

Causes of Cirrhosis-Related Portal Hypertension

• Alcohol use
• Viral hepatitis (hepatitis B, hepatitis C)
• Metabolic dysfunction–associated steatotic liver disease 
• Autoimmune hepatitis
• Primary biliary cholangitis
• Primary sclerosing cholangitis 
• Hereditary hemochromatosis
• Wilson disease
• α1-Antitrypsin deficiency

Causes of Noncirrhotic Portal Hypertension 

• Extrahepatic portal venous obstruction 
• Portal vein thrombosis
• Splenic vein thrombosis due to chronic pancreatitis, pancreatic pseudocysts, pancreatic neoplasms
• Infiltrative diseases such as mastocytosis and amyloidosis
• Congenital hepatic fibrosis
• Schistosomiasis
• Noncirrhotic portal fibrosis
• Drug-induced portal hypertension
• Hepatic venous outflow tract obstruction 
• Granulomatous disease, such as sarcoidosis
• Obstruction of the inferior vena cava
• Constrictive pericarditis
• Severe right-sided heart failure

Epidemiology

The exact prevalence of gastric varices is unknown. Results from 2 single-center prospective studies involving more than 500 patients with both cirrhotic and noncirrhotic portal hypertension estimated the prevalence of gastric varices as 15 to 20%.[7][8][9] With the advent of endoscopic ultrasonography, prevalence rates as high as 55% to 78% have been reported.[10] The incidence of bleeding from gastric varices is estimated at 10% to 30% in patients with underlying portal hypertension. The risk of gastric variceal hemorrhage increases with variceal size, the presence of red spots (red wales) on the varices, and cirrhosis severity based on the Child-Pugh score.[11][12] Unlike esophageal varices, gastric varices uncommonly present with acute variceal bleeding and are routinely discovered on screening esophagogastroduodenoscopy for varices in patients with portal hypertension. Results from a prospective study evaluating patients with cirrhosis and gastric varices found a cumulative risk for hemorrhage of 16%, 36%, and 44% at 1, 3, and 5 years, respectively.[11] 

Pathophysiology

Portal hypertension is a hemodynamic disorder commonly associated with liver cirrhosis and a clinical manifestation of noncirrhotic hepatic and extrahepatic disorders.[13] As previously mentioned, portal hypertension is the primary determinant implicated in gastric varix development. Normally, the portal vein receives blood from the coronary vein, the splenic vein, and the superior mesenteric vein. The normal hepatic venous pressure gradient, defined as the difference between the wedged hepatic vein pressure and the free hepatic venous pressure, ranges from 3 to 5 mm Hg.[14] When the hepatic venous pressure gradient increases to 10 mm Hg or greater, portal hypertension becomes clinically significant, resulting in complications such as ascites, gastroesophageal varix development, hepatic encephalopathy, and functional renal failure.[13] 

The pathophysiology of portal hypertension in cirrhosis is explained by various factors, including decreased hepatic vascular tone due to endothelial dysfunction, resulting in disequilibrium between vasoconstrictors and vasodilators, and increased hepatic resistance to portal blood flow from cellular damage, fibrosis, and regenerative nodular formation.[15] The ensuing portal hypertension also results in spontaneous portosystemic collateral shunts between the splenic vein and the left renal vein, commonly referred to as gastrorenal shunts. These collateral shunts, mediated by angiogenic factors such as vascular endothelial growth factor and vascular endothelial growth factor receptor 2, occur in approximately 85% of patients with gastric varices.[16][17][18] Approximately 15% of patients with gastric varices have various portosystemic venous pathways, such as the left inferior phrenic, pericardiac, and azygos-hemiazygos veins. Additionally, portal venous blood flow is aggravated by hyperdynamic circulation secondary to splanchnic vasodilation from increased production of endogenous vasodilators (nitric oxide, prostacyclin, and tumor necrosis factor) and increased cardiac output.[19] The increased pressure and portal blood flow in the portosystemic circulation due to these factors lead to gastric varices, which elevate intravariceal pressure and wall tension, increasing the risk of variceal rupture and a life-threatening gastrointestinal tract bleed.[20] A hepatic venous pressure gradient greater than 20 mm Hg is associated with increased rebleeding, increased variceal bleeding severity, and increased mortality.[21] 

Alternatively, gastric varices can occur in the absence of cirrhosis and with a normal hepatic venous pressure gradient due to segmental portal hypertension from splenic vein obstruction, such as thrombosis or stenosis as a sequela of pancreatic pathology (pancreatitis, pancreatic pseudocysts, or neoplasms).[22] This obstruction in the splenic vein causes shunting of the blood, resulting in the development of splenoportal collaterals, subsequent increased pressure in the submucosal veins of the fundus, and the formation of isolated gastric varices. Isolated gastric varices secondary to splenic vein thrombosis are considered distinct from gastric varices secondary to cirrhosis.[23]

History and Physical

History

In patients with a new diagnosis of cirrhosis of unknown etiology, clinicians should elicit a history of alcohol use (onset, quantity, and frequency of use), illicit drug use, and family history of liver disorders. In patients with decompensated cirrhosis of known etiology, clinicians should obtain a history of prior or ongoing bleeding (hematemesis, melena, or hematochezia), ascites (swelling, discomfort, fullness, lower extremity swelling, dyspnea, or orthopnea), and hepatic encephalopathy (confusion or excessive sleepiness). In patients without cirrhosis with incidental findings of gastric varices, clinicians should obtain a history of personal or familial thrombophilia and the presence of pancreatic disorders. Gastrointestinal tract hemorrhage from gastric varices typically presents with sudden-onset, large-volume blood loss (hematemesis, melena, or hematochezia), often associated with dizziness, lightheadedness, or syncope.

Physical Examination

A general examination includes vital signs to ensure hemodynamic stability, particularly in patients who report recent or ongoing gastrointestinal tract bleeding. A focused systemic examination evaluating for clinical signs of cirrhosis and portal hypertension should be performed, as listed below. Specific findings include the following:

Ocular:

• Scleral icterus

Neck:

• Elevated jugular venous pulse (right-sided heart failure)

Pulmonary:

• Pleural effusion (hepatohydrothorax)

Abdominal:

• Ascites (abdominal distension, flank fullness, fluid thrill, puddle sign, shifting dullness, or abdominal tenderness)
• Periumbilical collateral circulation (caput-medusae)
• Splenomegaly

Skin:

• Jaundice
• Palmar erythema
• Pitting edema
• Spider angiomata
• Terry nails

Musculoskeletal:

• Dupuytren contracture

Genitourinary:

• Scrotal edema
• Testicular atrophy

Neurological:

• Asterixis
• Disturbances in the sleep-wake cycle, lethargy, and somnolence (reflecting different grades of hepatic encephalopathy)

Miscellaneous:

• Fetor hepaticus
• Gynecomastia

Evaluation

Patients with a new diagnosis of cirrhosis should undergo a complete laboratory workup to ascertain the etiology of cirrhosis. In patients with decompensated cirrhosis presenting with acute variceal bleeding, clinicians should perform initial blood work, including a complete blood count, a comprehensive hepatitis panel, liver and renal function panels, a coagulation profile, and infectious disease studies, to evaluate for etiologies of acute decompensation.

• Diagnostic esophagogastroduodenoscopy is the gold standard screening test for gastric varices in patients with decompensated cirrhosis or incidental findings of gastric varices on cross-sectional imaging. 
• Endoscopic ultrasonography is useful for better characterization of gastric varices and serves as a therapeutic adjunct to confirm obliteration of gastric varices after treatment.[24]
• Transient elastography can be used to assess the severity of fibrosis in patients at risk of developing clinically significant portal vein hypertension.
• Hepatic venous pressure gradient measurement can be used to diagnose clinically significant portal hypertension, predict the development of gastric varices, and estimate the risk of variceal bleeding. Hepatic venous pressure gradient measurement is often performed during a transjugular liver biopsy through interventional radiology.
• Doppler ultrasonography of the liver, contrasted CT or MRI can be used to make a diagnosis of cirrhosis, assess for portosystemic collaterals and venous thrombosis, and evaluate other signs of decompensation, such as ascites and hepatocellular carcinoma.
• Doppler ultrasonography, CT or MRI angiography, and venous-phase celiac arteriography are imaging modalities that assess portal vasculature patency to exclude thrombosis.[2]
• Liver biopsy should be considered in patients with cirrhosis to clarify the etiology, particularly when laboratory workup has negative results or is equivocal. 

Treatment / Management

The optimal treatment of gastric varices is based on available local expertise, underlying anatomy, and, ideally, an interdisciplinary discussion with hepatology and interventional radiology. Gastroesophageal type 1 varices can be treated with endoscopic variceal banding, similar to esophageal varices. The treatment of cardiofundal (gastroesophageal varices type 2 and isolated gastric varices type 1) and ectopic varices depends on the acuity of presentation. The 2024 American Association for the Study of Liver Diseases (AASLD) guideline classifies treatment into 3 categories: primary prophylaxis, treatment of acute variceal bleeding, and secondary prophylaxis.[2][3]

Primary Prophylaxis

β-Blockers have been used as long-term prophylactic treatment for portal hypertension. The 2024 AASLD guidelines recommend nonselective β-blocker therapy, such as propranolol or nadolol, as primary prophylaxis for acute variceal hemorrhage from gastric varices, especially gastroesophageal varices type 1 or isolated gastric varices that have not bled. The primary prophylaxis of gastroesophageal type 1 varices is similar to that of esophageal varices.[2][3] 

In patients with high-risk cardiofundal varices, defined by 10 mm or greater size, red wale signs, or Child-Turcotte-Pugh class B or C, who are intolerant of or have contraindications to nonselective β-blocker therapy, cyanoacrylate glue injection can be considered, based on results from a randomized controlled trial demonstrating the efficacy of cyanoacrylate glue over nonselective β-blocker therapy in preventing the first bleeding episode, though there was no survival benefit.[25] Furthermore, due to the paucity of data and known complications associated with transjugular intrahepatic portosystemic shunt and balloon-occluded retrograde transvenous obliteration, the AASLD guidelines do not recommend these interventions for primary prophylaxis of fundal varices that have not bled.(A1)

Management of Acute Gastric Variceal Bleeding

The most crucial step in treating patients presenting with acute gastric variceal bleeding is admission to the intensive care unit for hemodynamic stabilization, respiratory status protection, and resuscitation. Red blood cell transfusions should be limited to a target hemoglobin level of approximately 8 g/dL to avoid elevating portal pressures and increasing the risk of further bleeding. Associated coagulopathy and thrombocytopenia should also be corrected. Empiric use of antibiotics, such as third-generation cephalosporins (eg, ceftriaxone), in patients with cirrhosis is recommended to reduce the risk of bacterial infections. Infections from bacterial translocation in active bleeding are associated with increased mortality rates.

Vasoactive agents, such as octreotide, somatostatin, and terlipressin, are advised to reduce portal pressures and collateral blood flow. Vasoactive agents are typically used for 2 to 5 days. Urgent upper endoscopy (within 12 h of presentation) should be performed for diagnosis and treatment due to high mortality rates in patients with cirrhosis. In situations where acute gastric variceal bleeding is suspected but urgent evaluation with upper endoscopy is not available, or the patient has massive bleeding not amenable to endoscopic intervention, balloon tamponade with the Sengstaken-Blakemore tube or the Minnesota tube can be performed at the bedside as a temporizing bridge to definitive therapy. In patients with acute gastric variceal bleeding, contrast-enhanced cross-sectional imaging should be obtained to delineate the portosystemic collateral anatomy and evaluate for portal thrombosis, thereby guiding therapy.

Endoscopic therapies:

Data regarding the role of endoscopic therapy for the treatment of bleeding gastric varices are limited. However, initial endoscopic evaluation is the mainstay in the management algorithm. Therapeutic options further depend on available local expertise. Current endoscopic interventions include endoscopic injection sclerotherapy, injection of cyanoacrylate-based tissue adhesives or thrombin, endoscopic coiling, and endoscopic variceal ligation.[26] Endoscopic variceal ligation can be considered for gastric varices along the lesser curvature, similar to esophageal varices.[2][27] Endoscopic injection sclerotherapy with sclerosing agents, such as alcohol, polidocanol, or tetradecyl sulfate, is associated with increased complications and rebleeding rates. Therefore, endoscopic injection sclerotherapy is not recommended in the treatment of acute gastric variceal bleeding, especially gastroesophageal varices type 2.[28][29] Direct injection of thrombin or fibrin glue has demonstrated success in results from a small case series and is comparable to cyanoacrylate glue injection in a prospective randomized trial.[30][31] However, these substances are expensive and not widely available as cyanoacrylate glue. (A1)

Cyanoacrylate glue is a class of synthetic glue mixed with lipiodol, an oily contrast agent, before injection into a varix. The mixture rapidly polymerizes into a hard acrylic plastic upon exposure to water or blood, leading to hemostasis.[28] Cyanoacrylate glue is currently the recommended therapeutic agent for definitive endoscopic treatment of gastric varices. Results from a meta-analysis by Qiao et al reported a higher rate of active bleeding control (odds ratio, 4.44; 95% CI, 1.14-17.30; P = .032), a lower rebleeding rate (odds ratio, 0.33; 95% CI, 0.18-0.60; P = .0004), and a lower gastric varix recurrence rate (relative risk, 0.26; 95% CI, 0.11-0.61; P = .002) in patients treated with cyanoacrylate injection compared with patients who were treated with endoscopic variceal ligation.[32] Adverse events associated with cyanoacrylate glue injection include the possibility of distal embolization before polymerization, leading to pulmonary embolism, splenic infarcts, stroke, or coronary emboli.(B2)

Endoscopic coiling involves pushing metal coils through a stylet into the feeder varix. These coils are coated with thrombogenic fibers and induce hemostasis. Results from a single-center randomized controlled trial and another retrospective study showed variceal obliteration rates of 90% and 73%, respectively, and rebleeding rates of 26% and 15%, respectively.[33][34] Endoscopic ultrasonography-guided therapy, such as cyanoacrylate glue injection and endoscopic coiling, is commonly performed under endoscopic ultrasonography guidance. Endoscopic ultrasonography allows precise identification of the feeder vessel by color Doppler before therapeutic intervention and gives visual confirmation of variceal obliteration after treatment. Recent data support the use of combination therapy with glue and coiling over monotherapy in achieving hemostasis with minimal adverse effects. A single-center trial randomized 60 participants with fundal varices to receive endoscopic ultrasonography–guided glue and coiling or endoscopic ultrasonography–guided coiling alone. Results showed 100% technical success in both arms, but the rebleeding rate was higher with coiling monotherapy compared with combined therapy (20% versus 3%).[33] Results from meta-analyses further support the safety and efficacy of combined therapy in the treatment of gastric varices.[35][36] Findings from the meta-analysis by McCarty et al showed that endoscopic ultrasonography–guided combination therapy with coil embolization and cyanoacrylate glue injection achieved higher technical and clinical success rates, with fewer adverse effects, compared with either endoscopic ultrasonography–guided coil or cyanoacrylate glue monotherapy. (A1)

Vascular therapies in interventional radiology:

Transjugular intrahepatic portosystemic shunt and balloon-occluded retrograde transvenous obliteration are alternative first-line therapies for treating acute gastric variceal bleeding, particularly if bleeding is not controlled with endoscopic intervention or the patient remains at high risk of rebleeding.[2] Transjugular intrahepatic portosystemic shunt involves creating an intrahepatic connection between the hepatic and portal venous systems, subsequently diverting portal venous flow into the systemic circulation and reducing portal pressures. Results from randomized controlled trials have shown that transjugular intrahepatic portosystemic shunt is more effective than cyanoacrylate injection in preventing rebleeding from gastric varices, with similar survival and complication rates.[37] Potential adverse effects include worsening hepatic encephalopathy, right heart strain, bleeding, and shunt dysfunction. Contraindications to transjugular intrahepatic portosystemic shunt placement include patients with uncontrolled hepatic encephalopathy, advanced heart failure, or thromboses preventing access to the portal or hepatic veins. (A1)

Balloon-occluded retrograde transvenous obliteration has emerged as a safe and clinically effective treatment option in treating gastric variceal bleeding, particularly if patients have associated refractory hepatic encephalopathy or a contraindication to transjugular intrahepatic portosystemic shunt.[38] This technique involves the retrograde injection of a sclerosing agent into the gastric varix after occluding the portosystemic shunt with an occlusion balloon under fluoroscopic guidance. The performance of balloon-occluded retrograde transvenous obliteration requires the presence of a spontaneous portosystemic shunt, such as a gastrorenal shunt or a gastrocaval shunt, which is present in 60% to 85% of cases.(B3)

Contrast-enhanced cross-sectional imaging (CT or MRI) should be performed to determine the feasibility of this procedure. Results from a meta-analysis of 24 studies involving 1016 patients by Park et al showed that the technical success rate for balloon-occluded retrograde transvenous obliteration was 96.4%, and the clinical success rate was 97.3%.[39] Moreover, findings from a randomized controlled trial from 2021 showed that balloon-occluded retrograde transvenous obliteration was more effective than cyanoacrylate glue in reducing rebleeding in patients with gastroesophageal varices type 2 and isolated gastric varices type 1.[40] Results from retrospective studies comparing transjugular intrahepatic portosystemic shunt with balloon-occluded retrograde transvenous obliteration showed that the active bleeding control rate, rebleeding rate, and complication rate were superior with balloon-occluded retrograde transvenous obliteration than with transjugular intrahepatic portosystemic shunt.[41][42] Complications of balloon-occluded retrograde transvenous obliteration include worsening of ascites and esophageal varices. Thus, the presence of large esophageal varices or significant ascites often precludes the procedure.(A1)

Recent refinements to the balloon-occluded retrograde transvenous obliteration procedure involve using plug-assisted transvenous obliteration or coil-assisted retrograde transvenous obliteration instead of the traditional indwelling balloon catheter with sclerosant injection. According to the most recent AASLD practice guidelines, coil-assisted retrograde transvenous obliteration and plug-assisted transvenous obliteration are recommended over balloon-occluded retrograde transvenous obliteration for the treatment of gastric varices, based on their clinical efficacy and safety profile.[43](A1)

Surgical intervention:

With the advent of newer minimally invasive and improved diagnostic and therapeutic techniques via endoscopy and interventional radiology, the role of surgical procedures in treating acute gastric variceal bleeding is limited and should be considered a last resort when the above measures fail. However, splenectomy or splenic artery embolization should be considered definitive therapy in patients presenting with acute gastric variceal bleeding secondary to sinistral or left-sided portal hypertension caused by splenic vein thrombosis. Splenectomy eliminates collateral venous flow and prevents future gastric variceal bleeding secondary to splenic vein thrombosis.[23]

Secondary Prophylaxis

Nonselective β-blockers in combination with endoscopic therapy (endoscopic variceal ligation or cyanoacrylate injection) are recommended as first-line therapy to prevent rebleeding in patients who recover from a gastroesophageal variceal type 1 hemorrhage.[3] Transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration is indicated as first-line therapy in patients recovering from gastric variceal hemorrhage secondary to gastroesophageal varices type 1 or isolated gastric varices type 1. A 2025 randomized controlled trial enrolled consecutive patients with cirrhosis and acute variceal bleeding from cardiofundal varices who achieved primary hemostasis by endoscopic ultrasonography–guided cyanoacrylate glue injection into 2 groups (endoscopic intervention with serial endoscopic ultrasonography–guided cyanoacrylate glue injection or radiology intervention with transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration). Results showed that transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration for secondary prophylaxis reduced rebleeding from gastric varices and rebleeding-related mortality.[44] Endoscopic ultrasonography–guided cyanoacrylate glue injection or endoscopic ultrasonography–guided coil embolization is a secondary prophylactic option for patients in whom transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration is not technically feasible.(A1)

Differential Diagnosis

Differential diagnosis of gastric varices manifesting as hematemesis includes common etiologies of upper gastrointestinal tract hemorrhage, such as:

• Peptic ulcer disease 
• Esophageal varices
• Acute gastric erosions
• Ulcerated submucosal lesions
• Malignant gastric ulcers
• Dieulafoy lesion
• Mallory-Weiss tear
• Portal hypertensive gastropathy 
• Gastric antral vascular ectasia 

Prognosis

Although the incidence of acute gastric variceal bleeding is lower than that of esophageal variceal bleeding, gastric varices have a higher propensity to bleed severely. Gastric variceal bleeding is often associated with treatment failure, rebleeding, and higher mortality than esophageal variceal bleeding. The overall prognosis depends on the severity of the underlying disease. Commonly used prognostic models, such as the Child-Pugh and Model for End-Stage Liver Disease scores, are useful for predicting the severity of underlying liver disease and estimating mortality risk.

Complications

Spontaneous rupture of gastric varices can result in the following complications:

• Aspiration
• Acute blood loss anemia
• Hemorrhagic shock
• Multiorgan failure
• Increased susceptibility to bacterial infections
• Death